Antibióticos para la prevención secundaria de la cardiopatía coronaria
Appendices
Appendix 1. Search strategies
| Database | Date searched | Search strategy |
| CENTRAL (Cochrane Library) | 09/12/2019 | #1 MeSH descriptor: [Coronary Disease] explode all trees #2 MeSH descriptor: [Myocardial Ischemia] explode all trees #3 (myocard* near/3 infarct*) #4 (coronary near/3 disease*) #5 (myocard* near/3 ischemi*) #6 (myocard* near/3 ischaem*) #7 (ischemic near/3 heart) #8 (ischaemic near/3 heart) #9 MeSH descriptor: [Atherosclerosis] explode all trees #10 atherosclero* #11 angina* #12 #1 or #2 or #3 or #4 or #5 or #6 or #7 or #8 or #9 or #10 or #11 #13 MeSH descriptor: [Anti‐Bacterial Agents] explode all trees #14 Penicillin* #15 cephalosporin* #16 carbapenem* #17 monobactam* #18 beta‐lactam* #19 (aminoglycoside*) #20 macrolide* #21 clindamycin* #22 MeSH descriptor: [Penicillins] explode all trees #23 MeSH descriptor: [Lactams] explode all trees #24 MeSH descriptor: [Tetracyclines] explode all trees #25 MeSH descriptor: [Aminoglycosides] explode all trees #26 MeSH descriptor: [Macrolides] explode all trees #27 MeSH descriptor: [Clindamycin] explode all trees #28 MeSH descriptor: [Chloramphenicol] explode all trees #29 MeSH descriptor: [Fusidic Acid] this term only #30 MeSH descriptor: [Vancomycin] this term only #31 MeSH descriptor: [Daptomycin] this term only #32 MeSH descriptor: [Polymyxins] explode all trees #33 (antibiotic* or anti‐bacterial* or anti‐infective*) #34 #13 or #14 or #15 or #16 or #17 or #18 or #19 or #20 or #21 or #22 or #23 or #24 or #25 or #26 or #27 or #28 or #29 or #30 or #31 or #32 or #33 #35 #12 and #34 |
| MEDLINE (Ovid) | 09/12/2019 | 1. exp Coronary Disease/ 2. exp Myocardial Ischemia/ 3. (myocard* adj3 infarct*).tw. 4. (coronary adj3 disease*).tw. 5. (myocard* adj3 ischemi*).tw. 6. (myocard* adj3 ischaem*).tw. 7. (ischemic adj3 heart).tw. 8. (ischaemic adj3 heart).tw. 9. exp Atherosclerosis/ 10. atheroscleropenici*.tw. 11. angina*.tw. 12. or/1‐11 13. Anti‐Bacterial Agents/ 14. Penicillin*.tw. 15. cephalosporin*.tw. 16. carbapenem*.tw. 17. monobactam*.tw. 18. beta‐lactam*.tw. 19. aminoglycoside*.tw. 20. macrolide*.tw. 21. clindamycin*.tw. 22. exp Penicillins/ 23. exp lactams/ or beta‐lactams/ 24. exp Tetracyclines/ 25. exp Aminoglycosides/ 26. exp Macrolides/ 27. exp Clindamycin/ 28. exp Chloramphenicol/ 29. Fusidic Acid/ 30. Vancomycin/ 31. Daptomycin/ 32. exp Polymyxins/ 33. (antibiotic* or anti‐bacterial* or anti‐infective*).tw. 34. or/13‐33 35. 12 and 34 36. randomized controlled trial.pt. 37. controlled clinical trial.pt. 38. randomized.ab. 39. placebo.ab. 40. drug therapy.fs. 41. randomly.ab. 42. trial.ab. 43. groups.ab. 44. 36 or 37 or 38 or 39 or 40 or 41 or 42 or 43 45. exp animals/ not humans.sh. 46. 44 not 45 47. 35 and 46 |
| Embase (Ovid) | 09/12/2019 | 1. exp coronary artery disease/ 2. exp heart muscle ischemia/ 3. (myocard* adj3 infarct*).tw. 4. (coronary adj3 disease*).tw. 5. (myocard* adj3 ischemi*).tw. 6. (myocard* adj3 ischaem*).tw. 7. (ischemic adj3 heart).tw. 8. (ischaemic adj3 heart).tw. 9. exp atherosclerosis/ 10. atheroscleropenici*.tw. 11. angina*.tw. 12. 1 or 2 or 3 or 4 or 5 or 6 or 7 or 8 or 9 or 10 or 11 13. antiinfective agent/ 14. Penicillin*.tw. 15. cephalosporin*.tw. 16. carbapenem*.tw. 17. monobactam*.tw. 18. beta‐lactam*.tw. 19. aminoglycoside*.tw. 20. macrolide*.tw. 21. clindamycin*.tw. 22. exp penicillin derivative/ 23. exp lactam/ 24. exp tetracycline derivative/ 25. exp aminoglycoside/ 26. exp macrolide/ 27. exp clindamycin/ 28. exp chloramphenicol/ 29. fusidic acid/ 30. vancomycin/ 31. daptomycin/ 32. exp polymyxin/ 33. (antibiotic* or anti‐bacterial* or anti‐infective*).tw. 34. 13 or 14 or 15 or 16 or 17 or 18 or 19 or 20 or 21 or 22 or 23 or 24 or 25 or 26 or 27 or 28 or 29 or 30 or 31 or 32 or 33 35. 12 and 34 36. random$.tw. 37. factorial$.tw. 38. crossover$.tw. 39. cross over$.tw. 40. cross‐over$.tw. 41. placebo$.tw. 42. (doubl$ adj blind$).tw. 43. (singl$ adj blind$).tw. 44. assign$.tw. 45. allocate$.tw. 46. volunteer$.tw. 47. crossover procedure/ 48. double blind procedure/ 49. randomized controlled trial/ 50. single blind procedure/ 51. 36 or 37 or 38 or 39 or 40 or 41 or 42 or 43 or 44 or 45 or 46 or 47 or 48 or 49 or 50 52. (animal/ or nonhuman/) not human/ 53. 51 not 52 54. 35 and 53 |
| SCI‐Expanded (Web of Science) | 09/12/2019 | # 32 #31 AND #30 # 31 TS=((random* or blind* or allocat* or assign* or trial* or placebo* or crossover* or cross‐over*)) # 30 #29 AND #9 # 29 #28 OR #27 OR #26 OR #25 OR #24 OR #23 OR #22 OR #21 OR #20 OR #19 OR #18 OR #17 OR #16 OR #15 OR #14 OR #13 OR #12 OR #11 OR #10 # 28 TS=(Polymyxin*) # 27 TS=(Daptomycin) # 26 TS=(Vancomycin) # 25 TS=(Fusidic Acid) # 24 TS=(Chloramphenicol) # 23 TS=(Clindamycin) # 22 TS=(Macrolide*) # 21 TS=(Aminoglycoside*) # 20 TS=(Tetracycline*) # 19 TS=(Lactam*) # 18 TS=((antibiotic* or anti‐bacterial* or anti‐infective*)) # 17 TS=((clindamycin*)) # 16 TS=((macrolide*)) # 15 TS=((aminoglycoside*)) # 14 TS=((beta‐lactam*)) # 13 TS=(monobactam*) # 12 TS=((carbapenem*)) # 11 TS=(cephalosporin*) # 10 TS=(Penicillin*) # 9 #8 OR #7 OR #6 OR #5 OR #4 OR #3 OR #2 OR #1 # 8 TS=((ANGINA*)) # 7 TS=(ATHEROSCLERO*) # 6 TS=((ISCHAEMIC NEAR/3 HEART)) # 5 TS=((ISCHEMIC NEAR/3 HEART)) # 4 TS=((MYOCARD* near/3 ISCHAEM*)) # 3 TS=((MYOCARD* near/3 ISCHEMI*)) # 2 TS=((CORONARY near/3 DISEASE*)) # 1 TS=((MYOCARD* near/3 INFARCT*)) |
| BIOSIS (Web of Science) | 09/12/2019 | # 32 #31 AND #30 # 31 TS=((random* or blind* or allocat* or assign* or trial* or placebo* or crossover* or cross‐over*)) # 30 #29 AND #9 # 29 #28 OR #27 OR #26 OR #25 OR #24 OR #23 OR #22 OR #21 OR #20 OR #19 OR #18 OR #17 OR #16 OR #15 OR #14 OR #13 OR #12 OR #11 OR #10 # 28 TS=(Polymyxin*) # 27 TS=(Daptomycin) # 26 TS=(Vancomycin) # 25 TS=(Fusidic Acid) # 24 TS=(Chloramphenicol) # 23 TS=(Clindamycin) # 22 TS=(Macrolide*) # 21 TS=(Aminoglycoside*) # 20 TS=(Tetracycline*) # 19 TS=(Lactam*) # 18 TS=((antibiotic* or anti‐bacterial* or anti‐infective*)) # 17 TS=((clindamycin*)) # 16 TS=((macrolide*)) # 15 TS=((aminoglycoside*)) # 14 TS=((beta‐lactam*)) # 13 TS=(monobactam*) # 12 TS=((carbapenem*)) # 11 TS=(cephalosporin*) # 10 TS=(Penicillin*) # 9 #8 OR #7 OR #6 OR #5 OR #4 OR #3 OR #2 OR #1 # 8 TS=((ANGINA*)) # 7 TS=(ATHEROSCLERO*) # 6 TS=((ISCHAEMIC NEAR/3 HEART)) # 5 TS=((ISCHEMIC NEAR/3 HEART)) # 4 TS=((MYOCARD* near/3 ISCHAEM*)) # 3 TS=((MYOCARD* near/3 ISCHEMI*)) # 2 TS=((CORONARY near/3 DISEASE*)) # 1 TS=((MYOCARD* near/3 INFARCT*)) |
| LILACS (Bireme) | 09/12/2019 | "myocard$ infarct$" or "coronary disease$" or "myocard$ ischemi$" or "myocard$ ischaem$" or "ischemic heart" or "ischaemic heart" or "atherosclero$" or "angina$" [Words] and "Polymyxin*" or "Daptomycin" or "Vancomycin" or "Fusidic Acid" or "Chloramphenicol" or "Clindamycin" or "Macrolide*" or "Aminoglycoside*" or "Tetracycline*" or "Lactam*" or "antibiotic*" or "anti‐bacterial*" or "anti‐infective*" or "clindamycin*" or "macrolide*" or "aminoglycoside*" or "beta‐lactam*" or "monobactam*" or "carbapenem*" or "cephalosporin*" or "Penicillin*" [Words] |
| Google Scholar | 25/12/2019 | (Trial) AND (Controlled OR clinical) AND (Randomised OR randomized) AND (coronary heart disease OR acute coronary syndrome OR myocardial infarction OR angina pectoris) AND (antibiotic OR macrolide OR quinolone OR tetracycline OR penicillin OR clarithromycin OR azithromycin OR erythromycin OR roxithromycin OR doxycycline OR gatifloxacine) |
| The Turning Research into Practice (TRIP) Database | 25/12/2019 | (Trial) AND (Controlled OR clinical) AND (Randomised OR randomized) AND (coronary heart disease OR acute coronary syndrome OR myocardial infarction OR angina pectoris) AND (antibiotic OR macrolide OR quinolone OR tetracycline OR penicillin OR clarithromycin OR azithromycin OR erythromycin OR roxithromycin OR doxycycline OR gatifloxacine) |
| Clinicaltrials.gov | 25/12/2019 | Interventional studies AND coronary disease AND antibiotics |
| EU Clinical Trial Registry | 25/12/2019 | (Trial) AND (Controlled OR clinical) AND (Randomised OR randomized) AND (coronary heart disease OR acute coronary syndrome OR myocardial infarction OR angina pectoris) AND (antibiotic OR macrolide OR quinolone OR tetracycline OR penicillin OR clarithromycin OR azithromycin OR erythromycin OR roxithromycin OR doxycycline OR gatifloxacine) |
| Chinese Clinical Trial Registry (ChCTR) | 25/12/2019 | (Heart) AND (randomized parallel controlled trial) |
| International Standard Randomised Controlled Trial Number (ISRCTN) registry | 25/12/2019 | Coronary AND randomised AND antibiotic |
| GSK Clinical Study Register | 25/12/2019 | Heart AND interventional |
| Pan African Clinical Trials Registry (PACTR) | 25/12/2019 | Heart |
| Australian New Zealand Clinical Trials Registry (ANZCTR) | 25/12/2019 | Randomised AND coronary heart disease |
| Clinical Trials Registry ‐ India (CTRI) | 25/12/2019 | Randomized parallel group trial AND heart |
| The World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) search portal | 25/12/2019 | (Trial) AND (Controlled OR clinical) AND (Randomised OR randomized) AND (coronary heart disease OR acute coronary syndrome OR myocardial infarction OR angina pectoris) AND (antibiotic OR macrolide OR quinolone OR tetracycline OR penicillin OR clarithromycin OR azithromycin OR erythromycin OR roxithromycin OR doxycycline OR gatifloxacine) |
Study flow chart.
'Risk of bias' summary: review authors' judgements about each risk of bias item for each included study. Multiple eligible treatments were used in two trials generating two further comparisons (= 38 trials reporting on 40 experimental groups).
'Risk of bias' graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
Funnel plot of comparison: 1 Antibiotics versus placebo for secondary prevention of coronary heart disease at maximum follow‐up, outcome: 1.1 ALL‐CAUSE MORTALITY.
Funnel plot of comparison: 1 Antibiotics versus placebo for secondary prevention of coronary heart disease at maximum follow‐up, outcome: 1.17 CARDIOVASCULAR MORTALITY.
Funnel plot of comparison: 1 Antibiotics versus placebo for secondary prevention of coronary heart disease at maximum follow‐up, outcome: 1.33 MYOCARDIAL INFARCTION.
Comparison 1: Antibiotics versus placebo for secondary prevention of coronary heart disease at maximum follow‐up, Outcome 1: ALL‐CAUSE MORTALITY
Comparison 1: Antibiotics versus placebo for secondary prevention of coronary heart disease at maximum follow‐up, Outcome 2: All‐cause mortality ‐ trials at low risk of bias
Comparison 1: Antibiotics versus placebo for secondary prevention of coronary heart disease at maximum follow‐up, Outcome 3: All‐cause mortality ‐ 'best‐worst case' scenario
Comparison 1: Antibiotics versus placebo for secondary prevention of coronary heart disease at maximum follow‐up, Outcome 4: All‐cause mortality ‐ 'worst‐best case' scenario
Comparison 1: Antibiotics versus placebo for secondary prevention of coronary heart disease at maximum follow‐up, Outcome 5: All‐cause mortality ‐ modified 'best‐worst case' scenario
Comparison 1: Antibiotics versus placebo for secondary prevention of coronary heart disease at maximum follow‐up, Outcome 6: All‐cause mortality ‐ modified 'worst‐best case' scenario
Comparison 1: Antibiotics versus placebo for secondary prevention of coronary heart disease at maximum follow‐up, Outcome 7: All‐cause mortality ‐ trials with optimal medical therapy
Comparison 1: Antibiotics versus placebo for secondary prevention of coronary heart disease at maximum follow‐up, Outcome 8: All‐cause mortality according to type of antibiotic
Comparison 1: Antibiotics versus placebo for secondary prevention of coronary heart disease at maximum follow‐up, Outcome 9: All‐cause mortality according to antibody status
Comparison 1: Antibiotics versus placebo for secondary prevention of coronary heart disease at maximum follow‐up, Outcome 10: All‐cause mortality according to use of statins
Comparison 1: Antibiotics versus placebo for secondary prevention of coronary heart disease at maximum follow‐up, Outcome 11: All‐cause mortality according to the mean age
Comparison 1: Antibiotics versus placebo for secondary prevention of coronary heart disease at maximum follow‐up, Outcome 12: All‐cause mortality according to clinical trial registration status
Comparison 1: Antibiotics versus placebo for secondary prevention of coronary heart disease at maximum follow‐up, Outcome 13: All‐cause mortality according to length of follow‐up
Comparison 1: Antibiotics versus placebo for secondary prevention of coronary heart disease at maximum follow‐up, Outcome 14: All‐cause mortality according to class of antibiotic
Comparison 1: Antibiotics versus placebo for secondary prevention of coronary heart disease at maximum follow‐up, Outcome 15: All‐cause mortality according to funding
Comparison 1: Antibiotics versus placebo for secondary prevention of coronary heart disease at maximum follow‐up, Outcome 16: All‐cause mortality according to control intervention
Comparison 1: Antibiotics versus placebo for secondary prevention of coronary heart disease at maximum follow‐up, Outcome 17: CARDIOVASCULAR MORTALITY
Comparison 1: Antibiotics versus placebo for secondary prevention of coronary heart disease at maximum follow‐up, Outcome 18: Cardiovascular mortality ‐ trials at low risk of bias
Comparison 1: Antibiotics versus placebo for secondary prevention of coronary heart disease at maximum follow‐up, Outcome 19: Cardiovascular mortality ‐ 'best‐worst case' scenario
Comparison 1: Antibiotics versus placebo for secondary prevention of coronary heart disease at maximum follow‐up, Outcome 20: Cardiovascular mortality ‐ 'worst‐best case' scenario
Comparison 1: Antibiotics versus placebo for secondary prevention of coronary heart disease at maximum follow‐up, Outcome 21: Cardiovascular mortality ‐ modified 'best‐worst case' scenario
Comparison 1: Antibiotics versus placebo for secondary prevention of coronary heart disease at maximum follow‐up, Outcome 22: Cardiovascular mortality ‐ modified 'worst‐best case' scenario
Comparison 1: Antibiotics versus placebo for secondary prevention of coronary heart disease at maximum follow‐up, Outcome 23: Cardiovascular mortality ‐ trials with optimal medical therapy
Comparison 1: Antibiotics versus placebo for secondary prevention of coronary heart disease at maximum follow‐up, Outcome 24: Cardiovascular mortality according to type of antibiotic
Comparison 1: Antibiotics versus placebo for secondary prevention of coronary heart disease at maximum follow‐up, Outcome 25: Cardiovascular mortality according to antibody status
Comparison 1: Antibiotics versus placebo for secondary prevention of coronary heart disease at maximum follow‐up, Outcome 26: Cardiovascular mortality according to use of statins
Comparison 1: Antibiotics versus placebo for secondary prevention of coronary heart disease at maximum follow‐up, Outcome 27: Cardiovascular mortality according to the mean age
Comparison 1: Antibiotics versus placebo for secondary prevention of coronary heart disease at maximum follow‐up, Outcome 28: Cardiovascular mortality according to clinical trial registration status
Comparison 1: Antibiotics versus placebo for secondary prevention of coronary heart disease at maximum follow‐up, Outcome 29: Cardiovascular mortality according to length of follow‐up
Comparison 1: Antibiotics versus placebo for secondary prevention of coronary heart disease at maximum follow‐up, Outcome 30: Cardiovascular mortality according to class of antibiotic
Comparison 1: Antibiotics versus placebo for secondary prevention of coronary heart disease at maximum follow‐up, Outcome 31: Cardiovascular mortality according to funding
Comparison 1: Antibiotics versus placebo for secondary prevention of coronary heart disease at maximum follow‐up, Outcome 32: Cardiovascular mortality according to control intervention
Comparison 1: Antibiotics versus placebo for secondary prevention of coronary heart disease at maximum follow‐up, Outcome 33: MYOCARDIAL INFARCTION
Comparison 1: Antibiotics versus placebo for secondary prevention of coronary heart disease at maximum follow‐up, Outcome 34: Myocardial infarction ‐ trials at low risk of bias
Comparison 1: Antibiotics versus placebo for secondary prevention of coronary heart disease at maximum follow‐up, Outcome 35: Myocardial infarction ‐ 'best‐worst case' scenario
Comparison 1: Antibiotics versus placebo for secondary prevention of coronary heart disease at maximum follow‐up, Outcome 36: Myocardial infarction ‐ 'worst‐best case' scenario
Comparison 1: Antibiotics versus placebo for secondary prevention of coronary heart disease at maximum follow‐up, Outcome 37: Myocardial infarction ‐ modified 'best‐worst case' scenario
Comparison 1: Antibiotics versus placebo for secondary prevention of coronary heart disease at maximum follow‐up, Outcome 38: Myocardial infarction ‐ modified 'worst‐best case' scenario
Comparison 1: Antibiotics versus placebo for secondary prevention of coronary heart disease at maximum follow‐up, Outcome 39: Myocardial infarction ‐ trials with optimal medical therapy
Comparison 1: Antibiotics versus placebo for secondary prevention of coronary heart disease at maximum follow‐up, Outcome 40: Myocardial infarction according to type of antibiotic
Comparison 1: Antibiotics versus placebo for secondary prevention of coronary heart disease at maximum follow‐up, Outcome 41: Myocardial infarction according to antibody status
Comparison 1: Antibiotics versus placebo for secondary prevention of coronary heart disease at maximum follow‐up, Outcome 42: Myocardial infarction according to use of statins
Comparison 1: Antibiotics versus placebo for secondary prevention of coronary heart disease at maximum follow‐up, Outcome 43: Myocardial infarction according to the mean age
Comparison 1: Antibiotics versus placebo for secondary prevention of coronary heart disease at maximum follow‐up, Outcome 44: Myocardial infarction according to clinical trial registration status
Comparison 1: Antibiotics versus placebo for secondary prevention of coronary heart disease at maximum follow‐up, Outcome 45: Myocardial infarction according to length of follow‐up
Comparison 1: Antibiotics versus placebo for secondary prevention of coronary heart disease at maximum follow‐up, Outcome 46: Myocardial infarction according to class of antibiotic
Comparison 1: Antibiotics versus placebo for secondary prevention of coronary heart disease at maximum follow‐up, Outcome 47: Myocardial infarction according to funding
Comparison 1: Antibiotics versus placebo for secondary prevention of coronary heart disease at maximum follow‐up, Outcome 48: Myocardial infarction according to control intervention
Comparison 1: Antibiotics versus placebo for secondary prevention of coronary heart disease at maximum follow‐up, Outcome 49: STROKE
Comparison 1: Antibiotics versus placebo for secondary prevention of coronary heart disease at maximum follow‐up, Outcome 50: Stroke ‐ trials at low risk of bias
Comparison 1: Antibiotics versus placebo for secondary prevention of coronary heart disease at maximum follow‐up, Outcome 51: Stroke ‐ 'best‐worst case' scenario
Comparison 1: Antibiotics versus placebo for secondary prevention of coronary heart disease at maximum follow‐up, Outcome 52: Stroke ‐ 'worst‐best case' scenario
Comparison 1: Antibiotics versus placebo for secondary prevention of coronary heart disease at maximum follow‐up, Outcome 53: Stroke ‐ modified 'best‐worst case' scenario
Comparison 1: Antibiotics versus placebo for secondary prevention of coronary heart disease at maximum follow‐up, Outcome 54: Stroke ‐ modified 'worst‐best case' scenario
Comparison 1: Antibiotics versus placebo for secondary prevention of coronary heart disease at maximum follow‐up, Outcome 55: Stroke ‐ trials with optimal medical therapy
Comparison 1: Antibiotics versus placebo for secondary prevention of coronary heart disease at maximum follow‐up, Outcome 56: Stroke according to type of antibiotic
Comparison 1: Antibiotics versus placebo for secondary prevention of coronary heart disease at maximum follow‐up, Outcome 57: Stroke according to antibody status
Comparison 1: Antibiotics versus placebo for secondary prevention of coronary heart disease at maximum follow‐up, Outcome 58: Stroke according to use of statins
Comparison 1: Antibiotics versus placebo for secondary prevention of coronary heart disease at maximum follow‐up, Outcome 59: Stroke according to the mean age
Comparison 1: Antibiotics versus placebo for secondary prevention of coronary heart disease at maximum follow‐up, Outcome 60: Stroke according to clinical trial registration status
Comparison 1: Antibiotics versus placebo for secondary prevention of coronary heart disease at maximum follow‐up, Outcome 61: Stroke according to length of follow‐up
Comparison 1: Antibiotics versus placebo for secondary prevention of coronary heart disease at maximum follow‐up, Outcome 62: Stroke according to class of antibiotic
Comparison 1: Antibiotics versus placebo for secondary prevention of coronary heart disease at maximum follow‐up, Outcome 63: Stroke according to funding
Comparison 1: Antibiotics versus placebo for secondary prevention of coronary heart disease at maximum follow‐up, Outcome 64: Stroke according to control intervention
Comparison 1: Antibiotics versus placebo for secondary prevention of coronary heart disease at maximum follow‐up, Outcome 65: SUDDEN CARDIAC DEATH
Comparison 1: Antibiotics versus placebo for secondary prevention of coronary heart disease at maximum follow‐up, Outcome 66: Sudden cardiac death ‐ trials at low risk of bias
Comparison 1: Antibiotics versus placebo for secondary prevention of coronary heart disease at maximum follow‐up, Outcome 67: Sudden cardiac death ‐ 'best‐worst case' scenario
Comparison 1: Antibiotics versus placebo for secondary prevention of coronary heart disease at maximum follow‐up, Outcome 68: Sudden cardiac death ‐ 'worst‐best case' scenario
Comparison 1: Antibiotics versus placebo for secondary prevention of coronary heart disease at maximum follow‐up, Outcome 69: Sudden cardiac death ‐ modified 'best‐worst case' scenario
Comparison 1: Antibiotics versus placebo for secondary prevention of coronary heart disease at maximum follow‐up, Outcome 70: Sudden cardiac death ‐ modified 'worst‐best case' scenario
Comparison 1: Antibiotics versus placebo for secondary prevention of coronary heart disease at maximum follow‐up, Outcome 71: Sudden cardiac death according to clinical trial registration status
Comparison 1: Antibiotics versus placebo for secondary prevention of coronary heart disease at maximum follow‐up, Outcome 72: Sudden cardiac death according to funding
Comparison 1: Antibiotics versus placebo for secondary prevention of coronary heart disease at maximum follow‐up, Outcome 73: Sudden cardiac death according to type of antibiotic
Comparison 1: Antibiotics versus placebo for secondary prevention of coronary heart disease at maximum follow‐up, Outcome 74: Sudden cardiac death according to antibody status
Comparison 1: Antibiotics versus placebo for secondary prevention of coronary heart disease at maximum follow‐up, Outcome 75: Sudden cardiac death according to use of statins
Comparison 1: Antibiotics versus placebo for secondary prevention of coronary heart disease at maximum follow‐up, Outcome 76: Sudden cardiac death according to the mean age
Comparison 1: Antibiotics versus placebo for secondary prevention of coronary heart disease at maximum follow‐up, Outcome 77: Sudden cardiac death according to length of follow‐up
Comparison 1: Antibiotics versus placebo for secondary prevention of coronary heart disease at maximum follow‐up, Outcome 78: Sudden cardiac death according to class of antibiotic
Comparison 1: Antibiotics versus placebo for secondary prevention of coronary heart disease at maximum follow‐up, Outcome 79: Sudden cardiac death according to control intervention
Comparison 1: Antibiotics versus placebo for secondary prevention of coronary heart disease at maximum follow‐up, Outcome 80: HOSPITALISATION FOR ANY CAUSE
Comparison 1: Antibiotics versus placebo for secondary prevention of coronary heart disease at maximum follow‐up, Outcome 81: REVASCULARISATION
Comparison 1: Antibiotics versus placebo for secondary prevention of coronary heart disease at maximum follow‐up, Outcome 82: UNSTABLE ANGINA PECTORIS
Comparison 2: Antibiotics versus placebo for secondary prevention of coronary heart disease at 24±6 months follow‐up, Outcome 1: ALL‐CAUSE MORTALITY
Comparison 2: Antibiotics versus placebo for secondary prevention of coronary heart disease at 24±6 months follow‐up, Outcome 2: All‐cause mortality ‐ trials at low risk of bias
Comparison 2: Antibiotics versus placebo for secondary prevention of coronary heart disease at 24±6 months follow‐up, Outcome 3: All‐cause mortality ‐ 'best‐worst case' scenario
Comparison 2: Antibiotics versus placebo for secondary prevention of coronary heart disease at 24±6 months follow‐up, Outcome 4: All‐cause mortality ‐ 'worst‐best case' scenario
Comparison 2: Antibiotics versus placebo for secondary prevention of coronary heart disease at 24±6 months follow‐up, Outcome 5: All‐cause mortality ‐ modified 'best‐worst case' scenario
Comparison 2: Antibiotics versus placebo for secondary prevention of coronary heart disease at 24±6 months follow‐up, Outcome 6: All‐cause mortality ‐ modified 'worst‐best case' scenario
Comparison 2: Antibiotics versus placebo for secondary prevention of coronary heart disease at 24±6 months follow‐up, Outcome 7: All‐cause mortality ‐ trials with optimal medical therapy
Comparison 2: Antibiotics versus placebo for secondary prevention of coronary heart disease at 24±6 months follow‐up, Outcome 8: All‐cause mortality according to type of antibiotic
Comparison 2: Antibiotics versus placebo for secondary prevention of coronary heart disease at 24±6 months follow‐up, Outcome 9: All‐cause mortality according to antibody status
Comparison 2: Antibiotics versus placebo for secondary prevention of coronary heart disease at 24±6 months follow‐up, Outcome 10: All‐cause mortality according to use of statins
Comparison 2: Antibiotics versus placebo for secondary prevention of coronary heart disease at 24±6 months follow‐up, Outcome 11: All‐cause mortality according to the mean age
Comparison 2: Antibiotics versus placebo for secondary prevention of coronary heart disease at 24±6 months follow‐up, Outcome 12: All‐cause mortality according to clinical trial registration status
Comparison 2: Antibiotics versus placebo for secondary prevention of coronary heart disease at 24±6 months follow‐up, Outcome 13: All‐cause mortality according to class of antibiotic
Comparison 2: Antibiotics versus placebo for secondary prevention of coronary heart disease at 24±6 months follow‐up, Outcome 14: All‐cause mortality according to funding
Comparison 2: Antibiotics versus placebo for secondary prevention of coronary heart disease at 24±6 months follow‐up, Outcome 15: All‐cause mortality according to control intervention
Comparison 2: Antibiotics versus placebo for secondary prevention of coronary heart disease at 24±6 months follow‐up, Outcome 16: CARDIOVASCULAR MORTALITY
Comparison 2: Antibiotics versus placebo for secondary prevention of coronary heart disease at 24±6 months follow‐up, Outcome 17: Cardiovascular mortality ‐ trials at low risk of bias
Comparison 2: Antibiotics versus placebo for secondary prevention of coronary heart disease at 24±6 months follow‐up, Outcome 18: Cardiovascular mortality ‐ 'best‐worst case' scenario
Comparison 2: Antibiotics versus placebo for secondary prevention of coronary heart disease at 24±6 months follow‐up, Outcome 19: Cardiovascular mortality ‐ 'worst‐best case' scenario
Comparison 2: Antibiotics versus placebo for secondary prevention of coronary heart disease at 24±6 months follow‐up, Outcome 20: Cardiovascular mortality ‐ modified 'best‐worst case' scenario
Comparison 2: Antibiotics versus placebo for secondary prevention of coronary heart disease at 24±6 months follow‐up, Outcome 21: Cardiovascular mortality ‐ modified 'worst‐best case' scenario
Comparison 2: Antibiotics versus placebo for secondary prevention of coronary heart disease at 24±6 months follow‐up, Outcome 22: Cardiovascular mortality ‐ trials with optimal medical therapy
Comparison 2: Antibiotics versus placebo for secondary prevention of coronary heart disease at 24±6 months follow‐up, Outcome 23: Cardiovascular mortality according to type of antibiotic
Comparison 2: Antibiotics versus placebo for secondary prevention of coronary heart disease at 24±6 months follow‐up, Outcome 24: Cardiovascular mortality according to antibody status
Comparison 2: Antibiotics versus placebo for secondary prevention of coronary heart disease at 24±6 months follow‐up, Outcome 25: Cardiovascular mortality according to use of statins
Comparison 2: Antibiotics versus placebo for secondary prevention of coronary heart disease at 24±6 months follow‐up, Outcome 26: Cardiovascular mortality according to the mean age
Comparison 2: Antibiotics versus placebo for secondary prevention of coronary heart disease at 24±6 months follow‐up, Outcome 27: Cardiovascular mortality according to clinical trial registration status
Comparison 2: Antibiotics versus placebo for secondary prevention of coronary heart disease at 24±6 months follow‐up, Outcome 28: Cardiovascular mortality according to class of antibiotic
Comparison 2: Antibiotics versus placebo for secondary prevention of coronary heart disease at 24±6 months follow‐up, Outcome 29: Cardiovascular mortality according to funding
Comparison 2: Antibiotics versus placebo for secondary prevention of coronary heart disease at 24±6 months follow‐up, Outcome 30: Cardiovascular mortality according to control intervention
Comparison 2: Antibiotics versus placebo for secondary prevention of coronary heart disease at 24±6 months follow‐up, Outcome 31: MYOCARDIAL INFARCTION
Comparison 2: Antibiotics versus placebo for secondary prevention of coronary heart disease at 24±6 months follow‐up, Outcome 32: Myocardial infarction ‐ trials at low risk of bias
Comparison 2: Antibiotics versus placebo for secondary prevention of coronary heart disease at 24±6 months follow‐up, Outcome 33: Myocardial infarction ‐ 'best‐worst case' scenario
Comparison 2: Antibiotics versus placebo for secondary prevention of coronary heart disease at 24±6 months follow‐up, Outcome 34: Myocardial infarction ‐ 'worst‐best case' scenario
Comparison 2: Antibiotics versus placebo for secondary prevention of coronary heart disease at 24±6 months follow‐up, Outcome 35: Myocardial infarction ‐ modified 'best‐worst case' scenario
Comparison 2: Antibiotics versus placebo for secondary prevention of coronary heart disease at 24±6 months follow‐up, Outcome 36: Myocardial infarction ‐ modified 'worst‐best case' scenario
Comparison 2: Antibiotics versus placebo for secondary prevention of coronary heart disease at 24±6 months follow‐up, Outcome 37: Myocardial infarction ‐ trials with optimal medical therapy
Comparison 2: Antibiotics versus placebo for secondary prevention of coronary heart disease at 24±6 months follow‐up, Outcome 38: Myocardial infarction according to type of antibiotic
Comparison 2: Antibiotics versus placebo for secondary prevention of coronary heart disease at 24±6 months follow‐up, Outcome 39: Myocardial infarction according to antibody status
Comparison 2: Antibiotics versus placebo for secondary prevention of coronary heart disease at 24±6 months follow‐up, Outcome 40: Myocardial infarction according to use of statins
Comparison 2: Antibiotics versus placebo for secondary prevention of coronary heart disease at 24±6 months follow‐up, Outcome 41: Myocardial infarction according to the mean age
Comparison 2: Antibiotics versus placebo for secondary prevention of coronary heart disease at 24±6 months follow‐up, Outcome 42: Myocardial infarction according to clinical trial registration status
Comparison 2: Antibiotics versus placebo for secondary prevention of coronary heart disease at 24±6 months follow‐up, Outcome 43: Myocardial infarction according to class of antibiotic
Comparison 2: Antibiotics versus placebo for secondary prevention of coronary heart disease at 24±6 months follow‐up, Outcome 44: Myocardial infarction according to funding
Comparison 2: Antibiotics versus placebo for secondary prevention of coronary heart disease at 24±6 months follow‐up, Outcome 45: Myocardial infarction according to control intervention
Comparison 2: Antibiotics versus placebo for secondary prevention of coronary heart disease at 24±6 months follow‐up, Outcome 46: STROKE
Comparison 2: Antibiotics versus placebo for secondary prevention of coronary heart disease at 24±6 months follow‐up, Outcome 47: Stroke ‐ trials at low risk of bias
Comparison 2: Antibiotics versus placebo for secondary prevention of coronary heart disease at 24±6 months follow‐up, Outcome 48: Stroke ‐ 'best‐worst case' scenario
Comparison 2: Antibiotics versus placebo for secondary prevention of coronary heart disease at 24±6 months follow‐up, Outcome 49: Stroke ‐ 'worst‐best case' scenario
Comparison 2: Antibiotics versus placebo for secondary prevention of coronary heart disease at 24±6 months follow‐up, Outcome 50: Stroke ‐ modified 'best‐worst case' scenario
Comparison 2: Antibiotics versus placebo for secondary prevention of coronary heart disease at 24±6 months follow‐up, Outcome 51: Stroke ‐ modified 'worst‐best case' scenario
Comparison 2: Antibiotics versus placebo for secondary prevention of coronary heart disease at 24±6 months follow‐up, Outcome 52: Stroke ‐ trials with optimal medical therapy
Comparison 2: Antibiotics versus placebo for secondary prevention of coronary heart disease at 24±6 months follow‐up, Outcome 53: Stroke according to type of antibiotic
Comparison 2: Antibiotics versus placebo for secondary prevention of coronary heart disease at 24±6 months follow‐up, Outcome 54: Stroke according to antibody status
Comparison 2: Antibiotics versus placebo for secondary prevention of coronary heart disease at 24±6 months follow‐up, Outcome 55: Stroke according to use of statins
Comparison 2: Antibiotics versus placebo for secondary prevention of coronary heart disease at 24±6 months follow‐up, Outcome 56: Stroke according to the mean age
Comparison 2: Antibiotics versus placebo for secondary prevention of coronary heart disease at 24±6 months follow‐up, Outcome 57: Stroke according to clinical trial registration status
Comparison 2: Antibiotics versus placebo for secondary prevention of coronary heart disease at 24±6 months follow‐up, Outcome 58: Stroke according to class of antibiotic
Comparison 2: Antibiotics versus placebo for secondary prevention of coronary heart disease at 24±6 months follow‐up, Outcome 59: Stroke according to funding
Comparison 2: Antibiotics versus placebo for secondary prevention of coronary heart disease at 24±6 months follow‐up, Outcome 60: Stroke according to control intervention
Comparison 2: Antibiotics versus placebo for secondary prevention of coronary heart disease at 24±6 months follow‐up, Outcome 61: SUDDEN CARDIAC DEATH
Comparison 2: Antibiotics versus placebo for secondary prevention of coronary heart disease at 24±6 months follow‐up, Outcome 62: Sudden cardiac death ‐ trials at low risk of bias
Comparison 2: Antibiotics versus placebo for secondary prevention of coronary heart disease at 24±6 months follow‐up, Outcome 63: Sudden cardiac death ‐ 'best‐worst case' scenario
Comparison 2: Antibiotics versus placebo for secondary prevention of coronary heart disease at 24±6 months follow‐up, Outcome 64: Sudden cardiac death ‐ 'worst‐best case' scenario
Comparison 2: Antibiotics versus placebo for secondary prevention of coronary heart disease at 24±6 months follow‐up, Outcome 65: Sudden cardiac death ‐ modified 'best‐worst case' scenario
Comparison 2: Antibiotics versus placebo for secondary prevention of coronary heart disease at 24±6 months follow‐up, Outcome 66: Sudden cardiac death ‐ modified 'worst‐best case' scenario
Comparison 2: Antibiotics versus placebo for secondary prevention of coronary heart disease at 24±6 months follow‐up, Outcome 67: Sudden cardiac death according to clinical trial registration status
Comparison 2: Antibiotics versus placebo for secondary prevention of coronary heart disease at 24±6 months follow‐up, Outcome 68: Sudden cardiac death according to funding
Comparison 2: Antibiotics versus placebo for secondary prevention of coronary heart disease at 24±6 months follow‐up, Outcome 69: Sudden cardiac death according to type of antibiotic
Comparison 2: Antibiotics versus placebo for secondary prevention of coronary heart disease at 24±6 months follow‐up, Outcome 70: Sudden cardiac death according to antibody status
Comparison 2: Antibiotics versus placebo for secondary prevention of coronary heart disease at 24±6 months follow‐up, Outcome 71: Sudden cardiac death according to use of statins
Comparison 2: Antibiotics versus placebo for secondary prevention of coronary heart disease at 24±6 months follow‐up, Outcome 72: Sudden cardiac death according to the mean age
Comparison 2: Antibiotics versus placebo for secondary prevention of coronary heart disease at 24±6 months follow‐up, Outcome 73: Sudden cardiac death according to class of antibiotic
Comparison 2: Antibiotics versus placebo for secondary prevention of coronary heart disease at 24±6 months follow‐up, Outcome 74: Sudden cardiac death according to control intervention
Comparison 2: Antibiotics versus placebo for secondary prevention of coronary heart disease at 24±6 months follow‐up, Outcome 75: HOSPITALISATION FOR ANY CAUSE
Comparison 2: Antibiotics versus placebo for secondary prevention of coronary heart disease at 24±6 months follow‐up, Outcome 76: REVASCULARISATION
Comparison 2: Antibiotics versus placebo for secondary prevention of coronary heart disease at 24±6 months follow‐up, Outcome 77: UNSTABLE ANGINA PECTORIS
| Antibiotics compared with placebo or no intervention for coronary heart disease at maximum follow‐up | ||||||
| Patient or population: patients with coronary heart disease Settings: any setting Intervention: any antibiotic Comparison: placebo or no intervention | ||||||
| Outcomes | Anticipated absolute effects* (95% CI) | Relative effect | No of Participants | Certainty of the evidence | Comments | |
|---|---|---|---|---|---|---|
| Risk with placebo or no intervention | Risk with antibiotics | |||||
| All‐cause mortality at maximum follow‐up. Follow‐up: mean 21.4 months (range 3 to 120 months). | 100 per 1000 | 106 per 1000 | RR 1.06 (0.99 to 1.13) | 25,774 (20 trials) | ⊕⊕⊕⊕ | Overall low risk of bias due to the four trials carrying most of the weight were either at overall low risk of bias or were low risk of bias in the majority of domains. Low risk of imprecision due to inclusion of more participants than the estimated optimal information size1 |
| Serious adverse event at maximum follow‐up. | ‐ | ‐ | ‐ | ‐ | ‐ | No data were reported in the included trials. |
| Quality of life at maximum follow‐up. | ‐ | ‐ | ‐ | ‐ | ‐ | No data were reported in the included trials. |
| Cardiovascular mortality at maximum follow‐up. Follow‐up: mean 72.0 months (range 24 to 120 months). | 167 per 1000 | 185 per 1000 | RR 1.11 (0.98 to 1.25) | 4674 (2 trials) | ⊕⊕⊕⊝ | The sensitivity analysis only including low risk of bias trials differed from the overall analysis. Hence, for this outcome, we based our primary analysis and primary conclusion on trials at low risk of bias. Overall low risk of bias due to the three trials carrying most of the weight were either at overall low risk of bias or were low risk of bias in the majority of domains. Low risk of imprecision due to the sample size being very large (> 4000 participants)3. |
| Myocardial infarction at maximum follow‐up. Follow‐up: mean 20.7 months (range 3 to 120 months). | 80 per 1000 | 76 per 1000 | RR 0.95 (0.88 to 1.03) | 25,523 (17 trials) | ⊕⊕⊕⊕ | Overall low risk of bias due to the four trials carrying most of the weight were either at overall low risk of bias or were low risk of bias in the majority of domains. Low risk of imprecision due to inclusion of more participants than the estimated optimal information size4. |
| Stroke at maximum follow‐up. Follow‐up: mean 31.9 months (range 6 to 120 months). | 55 per 1000 | 62 per 1000 | RR 1.14 (1.00 to 1.29) | 14,774 (9 trials) | ⊕⊕⊕⊕ | Overall low risk of bias due to the three trials carrying most of the weight were either at overall low risk of bias or were low risk of bias in the majority of domains. Low risk of imprecision due to the sample size being very large (> 4000 participants)5. The risk of publication bias could not be assessed due to too few included trials. |
| Sudden cardiac death at maximum follow‐up. Follow‐up: mean 69.3 months (range 18.5 to 120 months). | 84 per 1000 | 90 per 1000 (75 to 109) | RR 1.08 (0.90 to 1.31) | 4520 (2 trials) | ⊕⊕⊕⊝ | Overall low risk of bias due to both trials included in the meta‐analyses being at overall low risk of bias or low risk of bias in the majority of domains, respectively. Low risk of imprecision due to the sample size being very large (> 4000 participants)6. The risk of publication bias could not be assessed due to too few included trials. |
| *The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: Confidence interval; RR: Risk ratio. | ||||||
| GRADE Working Group grades of evidence | ||||||
| 1No downgrading for imprecision: the optimal information size according to the GRADE Handbook using a RRR of 15%, an incidence in the control group of 10.0%, an alpha of 2.5%, and a beta of 10% was estimated to be 18,576 participants and we included 25,774 participants. 2Downgrading one level due to serious indirectness: risk of difference between the population of interest and the included participants, and between the intervention of interest and the included interventions. 3No downgrading for imprecision: the optimal information size according to the GRADE Handbook using a RRR of 15%, an incidence of 16.7%, an alpha of 2.0%, and a beta of 10% was estimated to be 10,883 participants and we only included 4674 participants. Nevertheless, the sample size was very large (>4000 participants). 4No downgrading for imprecision: the optimal information size according to the GRADE Handbook using a RRR of 15%, an incidence of 8.09%, an alpha of 2.0%, and a beta of 10% was estimated to be 24,627 participants and we included 25,523 participants. 5No downgrading for imprecision: the optimal information size according to the GRADE Handbook using a RRR of 15%, an incidence of 5.49%, an alpha of 2.0%, and a beta of 10% was estimated to be 37,339 participants and we only included 14,774 participants. Nevertheless, the sample size was very large (>4000 participants). 6No downgrading for imprecision. the optimal information size according to the GRADE Handbook using a RRR of 15%, an incidence of 8.36%, an alpha of 2.0%, and a beta of 10% was estimated to be 23,782 participants and we only included 4520 participants. Nevertheless, the sample size was very large (>4000 participants). | ||||||
| Antibiotics compared with placebo or no intervention for coronary heart disease at 24±6 months follow‐up | ||||||
| Patient or population: patients with coronary heart disease Settings: any setting Intervention: any antibiotic Comparison: placebo or no intervention | ||||||
| Outcomes | Anticipated absolute effects* (95% CI) | Relative effect | No of Participants | Certainty of the evidence | Comments | |
|---|---|---|---|---|---|---|
| Risk with placebo or no intervention | Risk with antibiotics | |||||
| All‐cause mortality at 24±6 months follow‐up. Follow‐up: mean 23.3 months (range 18 to 30 months). | 50 per 1000 | 62 per 1000 | RR 1.25 (1.06 to 1.48) | 9517 (6 trials) | ⊕⊕⊕⊕ | Overall low risk of bias due to the three trials carrying most of the weight were either at overall low risk of bias or were low risk of bias in the majority of domains. Low risk of imprecision due to the sample size being very large (> 4000 participants)1. The risk of publication bias could not be assessed due to too few included trials. |
| Serious adverse event at 24±6 months follow‐up. | ‐ | ‐ | ‐ | ‐ | ‐ | No data were reported in the included trials. |
| Quality of life at 24±6 months follow‐up. | ‐ | ‐ | ‐ | ‐ | ‐ | No data were reported in the included trials. |
| Cardiovascular mortality at 24±6 months follow‐up. Follow‐up: mean 23.1 months (range 18 to 30 months). | 23 per 1000 | 34 per 1000 | RR 1.50 (1.17 to 1.91) | 9044 (5 trials) | ⊕⊕⊕⊕ | Overall low risk of bias due to the three trials carrying most of the weight were either at overall low risk of bias or were low risk of bias in the majority of domains. Low risk of imprecision due to the sample size being very large (> 4000 participants)2. The risk of publication bias could not be assessed due to too few included trials. |
| Myocardial infarction at 24±6 months follow‐up. Follow‐up: mean 24.3 months (range 18.5 to 30.0 months). | 68 per 1000 | 65 per 1000 | RR 0.95 (0.82 to 1.11) | 9457 (5 trials) | ⊕⊕⊕⊝ | Overall low risk of bias due to the two trials carrying most of the weight were either at overall low risk of bias or were low risk of bias in the majority of domains. Low risk of imprecision due to the sample size being very large (> 4000 participants)4. The risk of publication bias could not be assessed due to too few included trials. |
| Stroke at 24±6 months follow‐up. Follow‐up: mean 24.3 months (range 18.5 to 30 months). | 21 per 1000 | 25 per 1000 | RR 1.17 (0.90 to 1.52) | 9457 (5 trials) | ⊕⊕⊕⊕ | Overall low risk of bias due to the three trials carrying most of the weight were either at overall low risk of bias or were low risk of bias in the majority of domains. Low risk of imprecision due to the sample size being very large (> 4000 participants)5. The risk of publication bias could not be assessed due to too few included trials. |
| Sudden cardiac death at 24±6 months follow‐up. Follow‐up: mean 24.3 months (range 18.5 to 30 months). | 26 per 1000 | 44 per 1000 (33 to 63) | RR 1.77 (1.28 to 2.44) | 4520 (2 trials) | ⊕⊕⊕⊝ | Overall low risk of bias due to both trials included in the meta‐analyses being at overall low risk of bias or low risk of bias in the majority of domains, respectively. Low risk of imprecision due to the sample size being very large (> 4000 participants)7. The risk of publication bias could not be assessed due to too few included trials. |
| *The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: Confidence interval; RR: Risk ratio. | ||||||
| GRADE Working Group grades of evidence | ||||||
| 1No downgrade for imprecision: the optimal information size according to the GRADE Handbook using a RRR of 15%, an incidence of 4.98%, an alpha of 2.5%, and a beta of 10% was estimated to be 38,771 participants and we only included 9509 participants. Nevertheless, the sample size was very large (>4000 participants). 2No downgrade for imprecision: the optimal information size according to the GRADE Handbook using a RRR of 15%, an incidence of 2.25%, an alpha of 2.0%, and a beta of 10% was estimated to be 91,738 participants and we only included 9036 participants. Nevertheless, the sample size was very large (>4000 participants). 3Downgrading one level due to serious inconsistency: the statistical heterogeneity was I2 = 43%; P = 0.14. Moreover, the forest plot showed trials with results in opposite direction. 4No downgrade for imprecision: the optimal information size according to the GRADE Handbook using a RRR of 15%, an incidence of 6.85%, an alpha of 2.0%, and a beta of 10% was estimated to be 96,669 participants and we only included 9457 participants. Nevertheless, the sample size was very large (>4000 participants). 5No downgrade for imprecision: The optimal information size according to the GRADE Handbook using a RRR of 15%, an incidence of 2.11%, an alpha of 2.0%, and a beta of 10% was estimated to be 97,219 participants and we only included 9449 participants. Nevertheless, the sample size was very large (>4000 participants). 6Downgrading one level due to serious indirectness: Risk of difference between the population of interest and the included participants, and between the intervention of interest and the included interventions. 7No downgrade for imprecision: the optimal information size according to the GRADE Handbook using a RRR of 15%, an incidence of 2.59%, an alpha of 2.0%, and a beta of 10% was estimated to be 80,024 participants and we only included 4520 participants. Nevertheless, the sample size was very large (>4000 participants). | ||||||
| Domain | Description |
|---|---|
| Random sequence generation |
|
| Allocation concealment |
|
| Blinding of participants and personnel |
|
| Blinding of outcome assessment |
|
| Incomplete outcome data |
|
| Selective outcome reporting |
|
| Other risks of bias |
|
| Overall risk of bias |
|
| Trial | Year | Number of participants currently smoking | Number of participants with diabetes | Number of participants with hypertension | Number of participants with hyperlipidaemia |
| ACADEMIC | 1999 | 112 out of 302 | 34 out of 302 | 127 out of 302 | ‐ |
| ACES | 2005 | 542 out of 4012 | 883 out of 4012 | 2688 out of 4012 | 3309 of 4012 |
| Aleksiadi 2007 | 2007 | ‐ | ‐ | ‐ | ‐ |
| ANTIBIO | 2003 | 428 out of 851 | 139 out of 861 | 439 out of 851 | ‐ |
| AZACS | 2003 | 348 out of 1439 | 398 out of 1439 | 832 out of 1439 | 864 out of 1439 |
| Berg 2005 | 2005 | 92 out of 473 | 74 out of 473 | 195 out of 473 | 278 out of 473 |
| CLARICOR | 2006 | 1572 out of 4372 | 678 out of 4372 | 1761 out of 4372 | ‐ |
| CLARIFY | 2002 | 40 out of 148 | 28 out of 148 | 62 out of 148 | 113 out of 148 |
| Gabriel 2003l | 2003 | 4 out of 38 | 9 out of 38 | 14 out of 38 | 8 out of 38 |
| Gupta 2007 | 1997 | 19 out of 60 | 20 out of 60 | 11 out of 60 | 25 out of 60 |
| Hillis 2004 | 2004 | 25 out of 141 | 19 out of 141 | 57 out of 141 | ‐ |
| Hyodo 2004 | 2004 | 6 out of 31 | 8 out of 31 | 17 out of 31 | 17 out of 31 |
| Ikeoka 2009 | 2009 | 41 out of 82 | 0 out of 82 | 46 out of 82 | ‐ |
| ISAR‐3 | 2001 | 224 out of 1010 | 202 out of 1010 | 771 out of 1010 | ‐ |
| Jackson 1999 | 1999 | ‐ | ‐ | ‐ | ‐ |
| Kaehler 2005 | 2005 | 67 out of 327 | 18 out of 327 | 259 out of 327 | ‐ |
| Kim 2004 | 2004 | 55 out of 129 | 38 out of 129 | 69 out of 129 | 35 out of 129 |
| Kim 2012 | 2012 | 26 out of 50 | 4 out of 50 | 27 out of 50 | 8 out of 50 |
| Kormi 2014 | 2014 | ‐ | ‐ | ‐ | ‐ |
| Kuvin 2003 | 2003 | 32 out of 58 | 12 out of 58 | 34 out of 58 | 45 out of 58 |
| Leowattana 2001 | 2001 | 44 out of 84 | 37 out of 84 | 44 out of 84 | 53 out of 84 |
| MIDAS | 2003 | 21 out of 50 | 20 out of 50 | 39 out of 50 | 41 out of 50 |
| Parchure 2002 | 2002 | 5 out of 40 | 8 out of 40 | 12 out of 40 | 27 out of 40 |
| Pieniazek 2001 | 2001 | ‐ | ‐ | ‐ | ‐ |
| PROVE‐IT | 2005 | 1529 out of 4162 | 734 out of 4162 | 2091 out of 4162 | ‐ |
| Radoi 2003l | 2003 | 39 out of 109 | 27 out of 109 | 67 out of 109 | 78 out of 109 |
| ROXIS | 1997 | 53 out of 202 | 26 out of 202 | 112 out of 202 | 129 out of 202 |
| Sanati2019 | 2019 | ‐ | 26 out of 68 | 27 out of 68 | 26 out of 68 |
| Schulze 2013 | 2013 | 20 out of 42 | 15 out of 42 | 37 out of 42 | 37 out of 42 |
| Semaan 2000 | 2000 | ‐ | ‐ | ‐ | ‐ |
| Sinisalo 1998 | 1998 | ‐ | ‐ | 11 out of 33 | ‐ |
| Stojanovic 2011 | 2011 | ‐ | 18 out of 165 | 37 out of 165 | 29 out of 165 |
| Thomaidou 2017 | 2017 | 16 out of 40 | 15 out of 40 | 21 out of 40 | ‐ |
| TIPTOP | 2014 | 61 out of 80 | 23 out of 80 | 55 out of 80 | 54 out of 80 |
| Torgano 1999 | 1999 | ‐ | 23 out of 110 | 26 out of 110 | 15 out of 110 |
| Tüter 2007 | 2007 | ‐ | ‐ | 26 out of 36 | ‐ |
| WIZARD | 2003 | 1266 out of 7722 | 1637 out of 7722 | 3482 out of 7722 | 4786 out of 7722 |
| Ütük 2004 | 2004 | 52 out of 113 | 20 out of 113 | 34 out of 113 | 20 out of 113 |
| Trial | Year | All‐cause mortality (months) | Cardiovascular mortality (months) | Myocardial infarction (months) | Stroke (months) | Sudden cardiac death (months) | Hospitalisation for any cause (months) | Revascularisation (months) | Unstable angina pectoris (months) |
| ACADEMIC | 1999 | 24 | 24 | 24 | 24 | NR | 24 | 24 | 24 |
| ACES | 2005 | 47 | 47 | 47 | 47 | NR | 47 | 47 | 47 |
| Aleksiadi 2007 | 2007 | NR | NR | NR | NR | NR | NR | NR | NR |
| ANTIBIO | 2003 | 12 | NR | 12 | 12 | NR | 12 | 12 | 12 |
| AZACS | 2003 | 6 | NR | 6 | NR | NR | 6 | 6 | NR |
| Berg 2005 | 2005 | 24 | NR | 24 | 24 | NR | NR | 24 | 24 |
| CLARICOR | 2006 | 120 | 120 | 120 | 120 | 120 | NR | NR | 120 |
| CLARIFY | 2002 | 18.5 | 18.5 | 18.5 | 18.5 | 18.5 | NR | NR | 18.5 |
| Gabriel 2003 | 2003 | NR | NR | NR | NR | NR | NR | NR | NR |
| Gupta 1997 | 1997 | 18 | 18 | NR | NR | NR | NR | NR | NR |
| Hillis 2004 | 2004 | NR | NR | NR | NR | NR | NR | NR | NR |
| Hyodo2004 | 2004 | NR | NR | NR | NR | NR | NR | NR | NR |
| Ikeoka 2009 | 2009 | 6 | NR | NR | NR | NR | NR | NR | NR |
| ISAR‐3 | 2001 | 12 | NR | 12 | NR | NR | NR | NR | NR |
| Jackson 1999 | 1999 | NR | NR | NR | NR | NR | NR | NR | NR |
| Kaehler2005 | 2005 | 12 | 12 | 12 | 12 | NR | NR | 12 | NR |
| Kim 2004 | 2004 | 12 | 12 | 12 | NR | NR | NR | 12 | NR |
| Kim 2012 | 2012 | NR | NR | NR | NR | NR | NR | NR | NR |
| Kormi 2014 | 2014 | NR | NR | NR | NR | NR | NR | NR | NR |
| Kuvin 2003 | 2003 | NR | NR | NR | NR | NR | NR | NR | NR |
| Leowattana2001 | 2001 | 3 | 3 | 3 | NR | NR | NR | 3 | NR |
| MIDAS | 2003 | 6 | 6 | 6 | NR | NR | NR | NR | NR |
| Parchure 2002 | 2002 | NR | NR | NR | NR | NR | NR | NR | NR |
| Pieniazek 2001 | 2001 | NR | NR | NR | NR | NR | NR | NR | NR |
| PROVE‐IT | 2005 | 24 | 24 | 24 | 24 | NR | 24 | 24 | 24 |
| Radoi et al | 2003 | 52 | 52 | NR | NR | NR | NR | NR | NR |
| ROXIS | 1997 | 6 | 6 | 6 | NR | NR | NR | NR | NR |
| Sanati 2019 | 2019 | NR | NR | NR | NR | NR | NR | NR | NR |
| Schulze 2013 | 2013 | NR | NR | NR | NR | NR | NR | NR | NR |
| Semaan 2000 | 2000 | NR | NR | NR | NR | NR | NR | NR | NR |
| Sinisalo 1998 | 1998 | NR | NR | NR | NR | NR | NR | NR | NR |
| Stojanovic 2011 | 2011 | NR | NR | NR | NR | NR | NR | NR | NR |
| Thomaidou 2017 | 2017 | NR | NR | NR | NR | NR | NR | NR | NR |
| TIPTOP | 2014 | 6 | 6 | 6 | 6 | NR | 6 | NR | NR |
| Torgano 1999 | 1999 | NR | NR | NR | NR | NR | NR | NR | NR |
| Tüter 2007 | 2007 | NR | NR | NR | NR | NR | NR | NR | NR |
| WIZARD | 2003 | 14 | NR | 14 | NR | NR | 14 | 14 | 14 |
| Ütük 2004 | 2004 | 6 | 6 | 6 | NR | NR | NR | 6 | 6 |
| NR: Not reported. | |||||||||
| Trial | Year | All‐cause mortality (months) | Cardiovascular mortality (months) | Myocardial infarction (months) | Stroke (months) | Sudden cardiac death (months) | Hospitalisation for any cause (months) | Revascularisation (months) | Unstable angina pectoris (months) |
| ACADEMIC | 1999 | 24 | 24 | 24 | 24 | NR | 24 | 24 | 24 |
| ACES | 2005 | NR | NR | NR | NR | NR | NR | NR | NR |
| Aleksiadi 2007 | 2007 | NR | NR | NR | NR | NR | NR | NR | NR |
| ANTIBIO | 2003 | NR | NR | NR | NR | NR | NR | NR | NR |
| AZACS | 2003 | NR | NR | NR | NR | NR | NR | NR | NR |
| Berg 2005 | 2005 | 24 | NR | 24 | 24 | NR | NR | 24 | 24 |
| CLARICOR | 2006 | 30 | 30 | 30 | 30 | 30 | NR | NR | NR |
| CLARIFY | 2002 | 18.5 | 18.5 | 18.5 | 18.5 | 18.5 | NR | NR | 18.5 |
| Gabriel 2003 | 2003 | NR | NR | NR | NR | NR | NR | NR | NR |
| Gupta 1997 | 1997 | 18 | NR | NR | NR | NR | NR | NR | NR |
| Hillis 2004 | 2004 | NR | NR | NR | NR | NR | NR | NR | NR |
| Hyodo 2004 | 2004 | NR | NR | NR | NR | NR | NR | NR | NR |
| Ikeoka 2009 | 2009 | NR | NR | NR | NR | NR | NR | NR | NR |
| ISAR‐3 | 2001 | NR | NR | NR | NR | NR | NR | NR | NR |
| Jackson 1999 | 1999 | NR | NR | NR | NR | NR | NR | NR | NR |
| Kaehler 2005 | 2005 | NR | NR | NR | NR | NR | NR | NR | NR |
| Kim 2004 | 2004 | NR | NR | NR | NR | NR | NR | NR | NR |
| Kim 2012 | 2012 | NR | NR | NR | NR | NR | NR | NR | NR |
| Kormi 2014 | 2014 | NR | NR | NR | NR | NR | NR | NR | NR |
| Kuvin 2003 | 2003 | NR | NR | NR | NR | NR | NR | NR | NR |
| Leowattana 2001 | 2001 | NR | NR | NR | NR | NR | NR | NR | NR |
| MIDAS | 2003 | NR | NR | NR | NR | NR | NR | NR | NR |
| Parchure2002 | 2002 | NR | NR | NR | NR | NR | NR | NR | NR |
| Pieniazek 2001 | 2001 | NR | NR | NR | NR | NR | NR | NR | NR |
| PROVE‐IT | 2005 | 24 | 24 | 24 | 24 | NR | 24 | 24 | 24 |
| Radoi 2003 | 2003 | NR | NR | NR | NR | NR | NR | NR | NR |
| ROXIS | 1997 | NR | NR | NR | NR | NR | NR | NR | NR |
| Sanati 2019 | 2019 | NR | NR | NR | NR | NR | NR | NR | NR |
| Schulze 2013 | 2013 | NR | NR | NR | NR | NR | NR | NR | NR |
| Semaan2000 | 2000 | NR | NR | NR | NR | NR | NR | NR | NR |
| Sinisalo 1998 | 1998 | NR | NR | NR | NR | NR | NR | NR | NR |
| Stojanovic 2011 | 2011 | NR | NR | NR | NR | NR | NR | NR | NR |
| Thomaidou 2017 | 2017 | NR | NR | NR | NR | NR | NR | NR | NR |
| TIPTOP | 2014 | NR | NR | NR | NR | NR | NR | NR | NR |
| Torgano 1999 | 1999 | NR | NR | NR | NR | NR | NR | NR | NR |
| Tüter 2007 | 2007 | NR | NR | NR | NR | NR | NR | NR | NR |
| WIZARD | 2003 | NR | NR | NR | NR | NR | NR | NR | NR |
| Ütük 2004 | 2004 | NR | NR | NR | NR | NR | NR | NR | NR |
| NR: Not reported. | |||||||||
| Trial | Year | Type and number of serious adverse event (antibiotics group) | Type and number of serious adverse event (control group) |
| ACADEMIC | 1999 |
|
|
| ACES | 2005 |
|
|
| ANTIBIO | 2003 |
|
|
| AZACS | 2003 |
|
|
| Berg 2005 | 2005 |
|
|
| CLARICOR | 2006 |
|
|
| CLARIFY | 2002 |
|
|
| Gupta 1997 | 1997 |
|
|
| Hillis 2004 | 2004 |
|
|
| Ikeoka 2009 | 2009 |
|
|
| ISAR‐3 | 2001 |
|
|
| Jackson1999 | 1999 |
|
|
| Kaehler 2005 | 2005 |
|
|
| Kim 2004 | 2004 |
|
|
| Leowattana 2001 | 2001 |
|
|
| MIDAS | 2003 |
|
|
| PROVE‐IT | 2005 |
|
|
| Radoi 2003 | 2003 |
|
|
| ROXIS | 1997 |
|
|
| Sinisalo 1998 | 1998 |
|
|
| TIPTOP | 2014 |
|
|
| WIZARD | 2003 |
|
|
| Ütük 2004 | 2004 |
|
|
| Trial | Year | Type and number of serious adverse event (antibiotics group) | Type and number of serious adverse event (control group) |
| ACADEMIC | 1999 |
|
|
| ACES | 2005 |
|
|
| Berg 2005 | 2005 |
|
|
| CLARICOR | 2006 |
|
|
| CLARIFY | 2002 |
|
|
| Gupta 1997 | 1997 |
|
|
| PROVE‐IT | 2005 |
|
|
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1.1 ALL‐CAUSE MORTALITY Show forest plot | 20 | 25774 | Risk Ratio (M‐H, Random, 95% CI) | 1.06 [0.99, 1.13] |
| 1.2 All‐cause mortality ‐ trials at low risk of bias Show forest plot | 3 | 6113 | Risk Ratio (M‐H, Random, 95% CI) | 1.07 [0.99, 1.15] |
| 1.3 All‐cause mortality ‐ 'best‐worst case' scenario Show forest plot | 20 | 25815 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.98 [0.92, 1.04] |
| 1.4 All‐cause mortality ‐ 'worst‐best case' scenario Show forest plot | 20 | 25815 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.13 [1.06, 1.21] |
| 1.5 All‐cause mortality ‐ modified 'best‐worst case' scenario Show forest plot | 20 | 25815 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.01 [0.95, 1.08] |
| 1.6 All‐cause mortality ‐ modified 'worst‐best case' scenario Show forest plot | 20 | 25815 | Risk Ratio (M‐H, Random, 95% CI) | 1.09 [1.02, 1.16] |
| 1.7 All‐cause mortality ‐ trials with optimal medical therapy Show forest plot | 13 | 23294 | Risk Ratio (M‐H, Random, 95% CI) | 1.06 [0.99, 1.13] |
| 1.8 All‐cause mortality according to type of antibiotic Show forest plot | 20 | 25774 | Risk Ratio (M‐H, Random, 95% CI) | 1.06 [0.99, 1.13] |
| 1.8.1 Azithromycin | 7 | 13746 | Risk Ratio (M‐H, Random, 95% CI) | 0.98 [0.85, 1.14] |
| 1.8.2 Roxithromycin | 5 | 2491 | Risk Ratio (M‐H, Random, 95% CI) | 1.06 [0.71, 1.57] |
| 1.8.3 Clarithromycin | 4 | 5106 | Risk Ratio (M‐H, Random, 95% CI) | 1.08 [1.00, 1.16] |
| 1.8.4 Doxycycline | 2 | 160 | Risk Ratio (M‐H, Random, 95% CI) | 0.63 [0.06, 6.20] |
| 1.8.5 Gatifloxacin | 1 | 4162 | Risk Ratio (M‐H, Random, 95% CI) | 1.29 [0.89, 1.85] |
| 1.8.6 Spiramycin | 1 | 109 | Risk Ratio (M‐H, Random, 95% CI) | 0.84 [0.29, 2.49] |
| 1.9 All‐cause mortality according to antibody status Show forest plot | 20 | 25774 | Risk Ratio (M‐H, Random, 95% CI) | 1.06 [0.99, 1.13] |
| 1.9.1 People with antibodies | 3 | 8084 | Risk Ratio (M‐H, Random, 95% CI) | 0.93 [0.76, 1.14] |
| 1.9.2 People without antibodies | 0 | 0 | Risk Ratio (M‐H, Random, 95% CI) | Not estimable |
| 1.9.3 Mixed | 17 | 17690 | Risk Ratio (M‐H, Random, 95% CI) | 1.08 [1.01, 1.15] |
| 1.10 All‐cause mortality according to use of statins Show forest plot | 13 | 23680 | Risk Ratio (M‐H, Random, 95% CI) | 1.06 [1.00, 1.13] |
| 1.10.1 People with use of statins | 4 | 4514 | Risk Ratio (M‐H, Random, 95% CI) | 0.89 [0.44, 1.81] |
| 1.10.2 People without use of statins | 0 | 0 | Risk Ratio (M‐H, Random, 95% CI) | Not estimable |
| 1.10.3 Mixed | 9 | 19166 | Risk Ratio (M‐H, Random, 95% CI) | 1.06 [0.99, 1.13] |
| 1.11 All‐cause mortality according to the mean age Show forest plot | 20 | 25774 | Risk Ratio (M‐H, Random, 95% CI) | 1.06 [0.99, 1.13] |
| 1.11.1 0 to 59 years | 5 | 4573 | Risk Ratio (M‐H, Random, 95% CI) | 1.15 [0.83, 1.60] |
| 1.11.2 60 and above | 15 | 21201 | Risk Ratio (M‐H, Random, 95% CI) | 1.06 [0.99, 1.13] |
| 1.12 All‐cause mortality according to clinical trial registration status Show forest plot | 20 | 25774 | Risk Ratio (M‐H, Random, 95% CI) | 1.06 [0.99, 1.13] |
| 1.12.1 Pre‐registration | 4 | 16366 | Risk Ratio (M‐H, Random, 95% CI) | 1.05 [0.91, 1.21] |
| 1.12.2 Post‐registration | 1 | 4012 | Risk Ratio (M‐H, Random, 95% CI) | 1.09 [0.86, 1.36] |
| 1.12.3 No registration | 15 | 5396 | Risk Ratio (M‐H, Random, 95% CI) | 0.99 [0.75, 1.29] |
| 1.13 All‐cause mortality according to length of follow‐up Show forest plot | 20 | 25774 | Risk Ratio (M‐H, Random, 95% CI) | 1.06 [0.99, 1.13] |
| 1.13.1 Trials with less than 12 months follow‐up | 7 | 2080 | Risk Ratio (M‐H, Random, 95% CI) | 0.73 [0.46, 1.15] |
| 1.13.2 Trials with equal to or longer than 12 months follow‐up | 13 | 23694 | Risk Ratio (M‐H, Random, 95% CI) | 1.07 [1.00, 1.14] |
| 1.14 All‐cause mortality according to class of antibiotic Show forest plot | 20 | 25760 | Risk Ratio (M‐H, Random, 95% CI) | 1.06 [0.99, 1.13] |
| 1.14.1 Macrolide | 17 | 21438 | Risk Ratio (M‐H, Random, 95% CI) | 1.05 [0.99, 1.13] |
| 1.14.2 Tetracycline | 2 | 160 | Risk Ratio (M‐H, Random, 95% CI) | 0.63 [0.06, 6.20] |
| 1.14.3 Quinolone | 1 | 4162 | Risk Ratio (M‐H, Random, 95% CI) | 1.29 [0.89, 1.85] |
| 1.15 All‐cause mortality according to funding Show forest plot | 20 | 25774 | Risk Ratio (M‐H, Random, 95% CI) | 1.06 [0.99, 1.13] |
| 1.15.1 Industry funded or unknown funded trials | 11 | 19073 | Risk Ratio (M‐H, Random, 95% CI) | 1.04 [0.91, 1.18] |
| 1.15.2 Non‐industry funded trials | 9 | 6701 | Risk Ratio (M‐H, Random, 95% CI) | 1.07 [0.99, 1.15] |
| 1.16 All‐cause mortality according to control intervention Show forest plot | 20 | 25774 | Risk Ratio (M‐H, Random, 95% CI) | 1.06 [0.99, 1.13] |
| 1.16.1 Placebo‐controlled trials | 17 | 25442 | Risk Ratio (M‐H, Random, 95% CI) | 1.06 [1.00, 1.13] |
| 1.16.2 No control intervention | 3 | 332 | Risk Ratio (M‐H, Random, 95% CI) | 0.58 [0.25, 1.32] |
| 1.17 CARDIOVASCULAR MORTALITY Show forest plot | 14 | 14180 | Risk Ratio (M‐H, Random, 95% CI) | 1.08 [0.96, 1.20] |
| 1.18 Cardiovascular mortality ‐ trials at low risk of bias Show forest plot | 2 | 4674 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.11 [0.98, 1.25] |
| 1.19 Cardiovascular mortality ‐ 'best‐worst case' scenario Show forest plot | 14 | 14192 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.94 [0.84, 1.04] |
| 1.20 Cardiovascular mortality ‐ 'worst‐best case' scenario Show forest plot | 14 | 14192 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.22 [1.09, 1.36] |
| 1.21 Cardiovascular mortality ‐ modified 'best‐worst case' scenario Show forest plot | 14 | 14192 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.00 [0.89, 1.11] |
| 1.22 Cardiovascular mortality ‐ modified 'worst‐best case' scenario Show forest plot | 14 | 14192 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.15 [1.03, 1.28] |
| 1.23 Cardiovascular mortality ‐ trials with optimal medical therapy Show forest plot | 10 | 13407 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.07 [0.96, 1.20] |
| 1.24 Cardiovascular mortality according to type of antibiotic Show forest plot | 14 | 14180 | Risk Ratio (M‐H, Random, 95% CI) | 1.08 [0.96, 1.20] |
| 1.24.1 Azithromycin | 4 | 4503 | Risk Ratio (M‐H, Random, 95% CI) | 0.88 [0.65, 1.21] |
| 1.24.2 Roxithromycin | 3 | 613 | Risk Ratio (M‐H, Random, 95% CI) | 0.57 [0.16, 1.97] |
| 1.24.3 Clarithromycin | 3 | 4633 | Risk Ratio (M‐H, Random, 95% CI) | 1.06 [0.38, 2.93] |
| 1.24.4 Doxycycline | 2 | 160 | Risk Ratio (M‐H, Random, 95% CI) | 0.63 [0.06, 6.20] |
| 1.24.5 Gatifloxacin | 1 | 4162 | Risk Ratio (M‐H, Random, 95% CI) | 1.64 [0.93, 2.89] |
| 1.24.6 Spiramycin | 1 | 109 | Risk Ratio (M‐H, Random, 95% CI) | 0.84 [0.29, 2.49] |
| 1.25 Cardiovascular mortality according to antibody status Show forest plot | 14 | 14180 | Risk Ratio (M‐H, Random, 95% CI) | 1.08 [0.96, 1.20] |
| 1.25.1 People with antibodies | 2 | 362 | Risk Ratio (M‐H, Random, 95% CI) | 1.07 [0.33, 3.43] |
| 1.25.2 People without antibodies | 0 | 0 | Risk Ratio (M‐H, Random, 95% CI) | Not estimable |
| 1.25.3 Mixed | 12 | 13818 | Risk Ratio (M‐H, Random, 95% CI) | 1.06 [0.92, 1.22] |
| 1.26 Cardiovascular mortality according to use of statins Show forest plot | 8 | 13096 | Risk Ratio (M‐H, Random, 95% CI) | 1.06 [0.83, 1.37] |
| 1.26.1 People with use of statins | 4 | 4514 | Risk Ratio (M‐H, Random, 95% CI) | 0.86 [0.35, 2.16] |
| 1.26.2 People without use of statins | 0 | 0 | Risk Ratio (M‐H, Random, 95% CI) | Not estimable |
| 1.26.3 Mixed | 4 | 8582 | Risk Ratio (M‐H, Random, 95% CI) | 1.04 [0.82, 1.33] |
| 1.27 Cardiovascular mortality according to the mean age Show forest plot | 14 | 14180 | Risk Ratio (M‐H, Random, 95% CI) | 1.08 [0.96, 1.20] |
| 1.27.1 18 to 59 years | 5 | 4573 | Risk Ratio (M‐H, Random, 95% CI) | 1.22 [0.77, 1.92] |
| 1.27.2 60 and above | 9 | 9607 | Risk Ratio (M‐H, Random, 95% CI) | 1.07 [0.95, 1.20] |
| 1.28 Cardiovascular mortality according to clinical trial registration status Show forest plot | 14 | 14180 | Risk Ratio (M‐H, Random, 95% CI) | 1.08 [0.96, 1.20] |
| 1.28.1 Pre‐registration | 3 | 8644 | Risk Ratio (M‐H, Random, 95% CI) | 1.18 [0.77, 1.80] |
| 1.28.2 Post‐registration | 1 | 4012 | Risk Ratio (M‐H, Random, 95% CI) | 0.87 [0.63, 1.20] |
| 1.28.3 No registration | 10 | 1524 | Risk Ratio (M‐H, Random, 95% CI) | 0.86 [0.49, 1.52] |
| 1.29 Cardiovascular mortality according to length of follow‐up Show forest plot | 14 | 14180 | Risk Ratio (M‐H, Random, 95% CI) | 1.08 [0.96, 1.20] |
| 1.29.1 Trials with less than 12 months follow‐up | 5 | 559 | Risk Ratio (M‐H, Random, 95% CI) | 0.47 [0.19, 1.16] |
| 1.29.2 Trials with equal to or longer than 12 months follow‐up | 9 | 13621 | Risk Ratio (M‐H, Random, 95% CI) | 1.09 [0.97, 1.22] |
| 1.30 Cardiovascular mortality according to class of antibiotic Show forest plot | 14 | 14180 | Risk Ratio (M‐H, Random, 95% CI) | 1.08 [0.96, 1.20] |
| 1.30.1 Macrolide | 11 | 9858 | Risk Ratio (M‐H, Random, 95% CI) | 1.06 [0.95, 1.19] |
| 1.30.2 Tetracycline | 2 | 160 | Risk Ratio (M‐H, Random, 95% CI) | 0.63 [0.06, 6.20] |
| 1.30.3 Quinolone | 1 | 4162 | Risk Ratio (M‐H, Random, 95% CI) | 1.64 [0.93, 2.89] |
| 1.31 Cardiovascular mortality according to funding Show forest plot | 14 | 14180 | Risk Ratio (M‐H, Random, 95% CI) | 1.08 [0.96, 1.20] |
| 1.31.1 Industry funded or unknown funded trials | 7 | 9000 | Risk Ratio (M‐H, Random, 95% CI) | 1.04 [0.72, 1.51] |
| 1.31.2 Non‐industry funded trials | 7 | 5180 | Risk Ratio (M‐H, Random, 95% CI) | 1.09 [0.97, 1.24] |
| 1.32 Cardiovascular mortality according to control intervention Show forest plot | 14 | 14180 | Risk Ratio (M‐H, Random, 95% CI) | 1.08 [0.96, 1.20] |
| 1.32.1 Placebo‐controlled trials | 11 | 13848 | Risk Ratio (M‐H, Random, 95% CI) | 1.09 [0.97, 1.22] |
| 1.32.2 No control intervention | 3 | 332 | Risk Ratio (M‐H, Random, 95% CI) | 0.58 [0.25, 1.32] |
| 1.33 MYOCARDIAL INFARCTION Show forest plot | 17 | 25523 | Risk Ratio (M‐H, Random, 95% CI) | 0.95 [0.88, 1.03] |
| 1.34 Myocardial infarction ‐ trials at low risk of bias Show forest plot | 3 | 6113 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.96 [0.86, 1.07] |
| 1.35 Myocardial infarction ‐ 'best‐worst case' scenario Show forest plot | 17 | 25564 | Risk Ratio (M‐H, Random, 95% CI) | 0.82 [0.72, 0.94] |
| 1.36 Myocardial infarction ‐ 'worst‐best case' scenario Show forest plot | 17 | 25564 | Risk Ratio (M‐H, Random, 95% CI) | 1.05 [0.90, 1.24] |
| 1.37 Myocardial infarction ‐ modified 'best‐worst case' scenario Show forest plot | 17 | 25564 | Risk Ratio (M‐H, Random, 95% CI) | 0.91 [0.84, 0.99] |
| 1.38 Myocardial infarction ‐ modified 'worst‐best case' scenario Show forest plot | 17 | 25564 | Risk Ratio (M‐H, Random, 95% CI) | 1.00 [0.90, 1.10] |
| 1.39 Myocardial infarction ‐ trials with optimal medical therapy Show forest plot | 12 | 23327 | Risk Ratio (M‐H, Random, 95% CI) | 0.95 [0.88, 1.03] |
| 1.40 Myocardial infarction according to type of antibiotic Show forest plot | 17 | 25523 | Risk Ratio (M‐H, Random, 95% CI) | 0.95 [0.88, 1.03] |
| 1.40.1 Azithromycin | 5 | 13604 | Risk Ratio (M‐H, Random, 95% CI) | 0.98 [0.84, 1.14] |
| 1.40.2 Roxithromycin | 5 | 2491 | Risk Ratio (M‐H, Random, 95% CI) | 0.97 [0.66, 1.42] |
| 1.40.3 Clarithromycin | 4 | 5106 | Risk Ratio (M‐H, Random, 95% CI) | 0.60 [0.30, 1.22] |
| 1.40.4 Doxycycline | 2 | 160 | Risk Ratio (M‐H, Random, 95% CI) | 1.32 [0.10, 17.36] |
| 1.40.5 Gatifloxacin | 1 | 4162 | Risk Ratio (M‐H, Random, 95% CI) | 0.89 [0.72, 1.12] |
| 1.40.6 Spiramycin | 0 | 0 | Risk Ratio (M‐H, Random, 95% CI) | Not estimable |
| 1.41 Myocardial infarction according to antibody status Show forest plot | 17 | 25523 | Risk Ratio (M‐H, Random, 95% CI) | 0.95 [0.88, 1.03] |
| 1.41.1 People with antibodies | 2 | 8024 | Risk Ratio (M‐H, Random, 95% CI) | 0.94 [0.75, 1.16] |
| 1.41.2 People without antibodies | 0 | 0 | Risk Ratio (M‐H, Random, 95% CI) | Not estimable |
| 1.41.3 Mixed | 15 | 17499 | Risk Ratio (M‐H, Random, 95% CI) | 0.95 [0.87, 1.04] |
| 1.42 Myocardial infarction according to use of statins Show forest plot | 12 | 23598 | Risk Ratio (M‐H, Random, 95% CI) | 0.95 [0.88, 1.03] |
| 1.42.1 People with use of statins | 4 | 4514 | Risk Ratio (M‐H, Random, 95% CI) | 0.88 [0.71, 1.10] |
| 1.42.2 People without use of statins | 0 | 0 | Risk Ratio (M‐H, Random, 95% CI) | Not estimable |
| 1.42.3 Mixed | 8 | 19084 | Risk Ratio (M‐H, Random, 95% CI) | 0.96 [0.88, 1.05] |
| 1.43 Myocardial infarction according to the mean age Show forest plot | 17 | 25523 | Risk Ratio (M‐H, Random, 95% CI) | 0.95 [0.88, 1.03] |
| 1.43.1 18 to 59 years | 3 | 4404 | Risk Ratio (M‐H, Random, 95% CI) | 0.89 [0.71, 1.10] |
| 1.43.2 60 and above | 14 | 21119 | Risk Ratio (M‐H, Random, 95% CI) | 0.96 [0.88, 1.05] |
| 1.44 Myocardial infarction according to clinical trial registration status Show forest plot | 17 | 25523 | Risk Ratio (M‐H, Random, 95% CI) | 0.95 [0.88, 1.03] |
| 1.44.1 Pre‐registration | 4 | 16366 | Risk Ratio (M‐H, Random, 95% CI) | 0.95 [0.87, 1.04] |
| 1.44.2 Post‐registration | 1 | 4012 | Risk Ratio (M‐H, Random, 95% CI) | 1.05 [0.83, 1.32] |
| 1.44.3 No registration | 12 | 5145 | Risk Ratio (M‐H, Random, 95% CI) | 0.81 [0.61, 1.08] |
| 1.45 Myocardial infarction according to length of follow‐up Show forest plot | 17 | 25523 | Risk Ratio (M‐H, Random, 95% CI) | 0.95 [0.88, 1.03] |
| 1.45.1 Trials with less than 12 months follow‐up | 6 | 1998 | Risk Ratio (M‐H, Random, 95% CI) | 0.70 [0.42, 1.15] |
| 1.45.2 Trials with equal to or longer than 12 months follow‐up | 11 | 23525 | Risk Ratio (M‐H, Random, 95% CI) | 0.96 [0.88, 1.04] |
| 1.46 Myocardial infarction according to class of antibiotic Show forest plot | 17 | 25523 | Risk Ratio (M‐H, Random, 95% CI) | 0.95 [0.88, 1.03] |
| 1.46.1 Macrolide | 14 | 21201 | Risk Ratio (M‐H, Random, 95% CI) | 0.96 [0.88, 1.05] |
| 1.46.2 Tetracycline | 2 | 160 | Risk Ratio (M‐H, Random, 95% CI) | 1.32 [0.10, 17.36] |
| 1.46.3 Quinolone | 1 | 4162 | Risk Ratio (M‐H, Random, 95% CI) | 0.89 [0.72, 1.12] |
| 1.47 Myocardial infarction according to funding Show forest plot | 17 | 25523 | Risk Ratio (M‐H, Random, 95% CI) | 0.95 [0.88, 1.03] |
| 1.47.1 Industry funded or unknown funded trials | 10 | 18964 | Risk Ratio (M‐H, Random, 95% CI) | 0.94 [0.84, 1.07] |
| 1.47.2 Non‐industry funded trials | 7 | 6559 | Risk Ratio (M‐H, Random, 95% CI) | 0.96 [0.86, 1.07] |
| 1.48 Myocardial infarction according to control intervention Show forest plot | 17 | 25515 | Risk Ratio (M‐H, Random, 95% CI) | 0.95 [0.88, 1.03] |
| 1.48.1 Placebo‐controlled trials | 15 | 25292 | Risk Ratio (M‐H, Random, 95% CI) | 0.95 [0.88, 1.04] |
| 1.48.2 No control intervention | 2 | 223 | Risk Ratio (M‐H, Random, 95% CI) | 0.38 [0.09, 1.58] |
| 1.49 STROKE Show forest plot | 9 | 14774 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.14 [1.00, 1.29] |
| 1.50 Stroke ‐ trials at low risk of bias Show forest plot | 2 | 4674 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.14 [0.99, 1.31] |
| 1.51 Stroke ‐ 'best‐worst case' scenario Show forest plot | 9 | 14779 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.98 [0.87, 1.11] |
| 1.52 Stroke ‐ 'worst‐best case' scenario Show forest plot | 9 | 14779 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.29 [1.14, 1.45] |
| 1.53 Stroke ‐ modified 'best‐worst case' scenario Show forest plot | 9 | 14779 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.05 [0.93, 1.19] |
| 1.54 Stroke ‐ modified 'worst‐best case' scenario Show forest plot | 9 | 14779 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.21 [1.07, 1.37] |
| 1.55 Stroke ‐ trials with optimal medical therapy Show forest plot | 6 | 13672 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.13 [0.99, 1.28] |
| 1.56 Stroke according to type of antibiotic Show forest plot | 9 | 14774 | Risk Ratio (M‐H, Random, 95% CI) | 1.14 [1.00, 1.29] |
| 1.56.1 Azithromycin | 2 | 4314 | Risk Ratio (M‐H, Random, 95% CI) | 1.05 [0.59, 1.85] |
| 1.56.2 Roxithromycin | 2 | 1195 | Risk Ratio (M‐H, Random, 95% CI) | 1.49 [0.21, 10.66] |
| 1.56.3 Clarithromycin | 3 | 4993 | Risk Ratio (M‐H, Random, 95% CI) | 1.16 [1.01, 1.32] |
| 1.56.4 Gatifloxacin | 1 | 4162 | Risk Ratio (M‐H, Random, 95% CI) | 1.05 [0.59, 1.88] |
| 1.56.5 Doxycycline | 1 | 110 | Risk Ratio (M‐H, Random, 95% CI) | 0.50 [0.05, 5.36] |
| 1.57 Stroke according to antibody status Show forest plot | 9 | 14774 | Risk Ratio (M‐H, Random, 95% CI) | 1.14 [1.00, 1.29] |
| 1.57.1 People with antibodies | 1 | 302 | Risk Ratio (M‐H, Random, 95% CI) | 0.34 [0.04, 3.21] |
| 1.57.2 People without antibodies | 0 | 0 | Risk Ratio (M‐H, Random, 95% CI) | Not estimable |
| 1.57.3 Mixed | 8 | 14472 | Risk Ratio (M‐H, Random, 95% CI) | 1.14 [1.01, 1.29] |
| 1.58 Stroke according to use of statins Show forest plot | 7 | 14145 | Risk Ratio (M‐H, Random, 95% CI) | 1.14 [1.00, 1.29] |
| 1.58.1 People with use of statins | 2 | 4272 | Risk Ratio (M‐H, Random, 95% CI) | 1.01 [0.57, 1.77] |
| 1.58.2 People without use of statins | 0 | 0 | Risk Ratio (M‐H, Random, 95% CI) | Not estimable |
| 1.58.3 Mixed | 5 | 9873 | Risk Ratio (M‐H, Random, 95% CI) | 1.15 [1.01, 1.30] |
| 1.59 Stroke according to the mean age Show forest plot | 9 | 14774 | Risk Ratio (M‐H, Random, 95% CI) | 1.14 [1.00, 1.29] |
| 1.59.1 18 to 59 years | 1 | 4162 | Risk Ratio (M‐H, Random, 95% CI) | 1.05 [0.59, 1.88] |
| 1.59.2 60 and above | 8 | 10612 | Risk Ratio (M‐H, Random, 95% CI) | 1.14 [1.00, 1.30] |
| 1.60 Stroke according to clinical trial registration status Show forest plot | 9 | 14774 | Risk Ratio (M‐H, Random, 95% CI) | 1.14 [1.00, 1.29] |
| 1.60.1 Pre‐registration | 3 | 8644 | Risk Ratio (M‐H, Random, 95% CI) | 1.14 [1.00, 1.30] |
| 1.60.2 Post‐registration | 1 | 4012 | Risk Ratio (M‐H, Random, 95% CI) | 1.13 [0.74, 1.72] |
| 1.60.3 No registration | 5 | 2118 | Risk Ratio (M‐H, Random, 95% CI) | 1.11 [0.59, 2.09] |
| 1.61 Stroke according to length of follow‐up Show forest plot | 9 | 14774 | Risk Ratio (M‐H, Random, 95% CI) | 1.14 [1.00, 1.29] |
| 1.61.1 Trials with less than 12 months follow‐up | 1 | 110 | Risk Ratio (M‐H, Random, 95% CI) | 0.50 [0.05, 5.36] |
| 1.61.2 Trials with equal to or longer than 12 months follow‐up | 8 | 14664 | Risk Ratio (M‐H, Random, 95% CI) | 1.14 [1.01, 1.29] |
| 1.62 Stroke according to class of antibiotic Show forest plot | 9 | 14774 | Risk Ratio (M‐H, Random, 95% CI) | 1.14 [1.00, 1.29] |
| 1.62.1 Macrolide | 7 | 10502 | Risk Ratio (M‐H, Random, 95% CI) | 1.14 [1.01, 1.30] |
| 1.62.2 Tetracycline | 1 | 110 | Risk Ratio (M‐H, Random, 95% CI) | 0.50 [0.05, 5.36] |
| 1.62.3 Quinolone | 1 | 4162 | Risk Ratio (M‐H, Random, 95% CI) | 1.05 [0.59, 1.88] |
| 1.63 Stroke according to funding Show forest plot | 9 | 14774 | Risk Ratio (M‐H, Random, 95% CI) | 1.14 [1.00, 1.29] |
| 1.63.1 Industry funded or unknown funded trials | 6 | 9990 | Risk Ratio (M‐H, Random, 95% CI) | 1.13 [0.83, 1.52] |
| 1.63.2 Non‐industry funded trials | 3 | 4784 | Risk Ratio (M‐H, Random, 95% CI) | 1.14 [0.99, 1.31] |
| 1.64 Stroke according to control intervention Show forest plot | 9 | 14774 | Risk Ratio (M‐H, Random, 95% CI) | 1.14 [1.00, 1.29] |
| 1.64.1 Placebo‐controlled trials | 8 | 14664 | Risk Ratio (M‐H, Random, 95% CI) | 1.14 [1.01, 1.29] |
| 1.64.2 No control intervention | 1 | 110 | Risk Ratio (M‐H, Random, 95% CI) | 0.50 [0.05, 5.36] |
| 1.65 SUDDEN CARDIAC DEATH Show forest plot | 2 | 4520 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.08 [0.90, 1.31] |
| 1.66 Sudden cardiac death ‐ trials at low risk of bias Show forest plot | 1 | 4372 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.08 [0.89, 1.30] |
| 1.67 Sudden cardiac death ‐ 'best‐worst case' scenario Show forest plot | 2 | 4521 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.00 [0.83, 1.20] |
| 1.68 Sudden cardiac death ‐ 'worst‐best case' scenario Show forest plot | 2 | 4521 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.14 [0.95, 1.37] |
| 1.69 Sudden cardiac death ‐ modified 'best‐worst case' scenario Show forest plot | 2 | 4521 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.04 [0.86, 1.25] |
| 1.70 Sudden cardiac death ‐ modified 'worst‐best case' scenario Show forest plot | 2 | 4521 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.11 [0.92, 1.34] |
| 1.71 Sudden cardiac death according to clinical trial registration status Show forest plot | 2 | 4520 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.08 [0.90, 1.31] |
| 1.71.1 Pre‐registration | 1 | 4372 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.08 [0.89, 1.30] |
| 1.71.2 Post‐registration | 0 | 0 | Risk Ratio (M‐H, Fixed, 95% CI) | Not estimable |
| 1.71.3 No registration | 1 | 148 | Risk Ratio (M‐H, Fixed, 95% CI) | 3.00 [0.12, 72.47] |
| 1.72 Sudden cardiac death according to funding Show forest plot | 2 | 4520 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.08 [0.90, 1.31] |
| 1.72.1 Industry funded or unknown funded trials | 1 | 148 | Risk Ratio (M‐H, Fixed, 95% CI) | 3.00 [0.12, 72.47] |
| 1.72.2 Non‐industry funded trials | 1 | 4372 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.08 [0.89, 1.30] |
| 1.73 Sudden cardiac death according to type of antibiotic Show forest plot | 2 | 4520 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.08 [0.90, 1.31] |
| 1.73.1 Clarithromycin | 2 | 4520 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.08 [0.90, 1.31] |
| 1.74 Sudden cardiac death according to antibody status Show forest plot | 2 | 4520 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.08 [0.90, 1.31] |
| 1.74.1 People with antibodies | 0 | 0 | Risk Ratio (M‐H, Fixed, 95% CI) | Not estimable |
| 1.74.2 People without antibodies | 0 | 0 | Risk Ratio (M‐H, Fixed, 95% CI) | Not estimable |
| 1.74.3 Mixed | 2 | 4520 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.08 [0.90, 1.31] |
| 1.75 Sudden cardiac death according to use of statins Show forest plot | 2 | 4520 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.08 [0.90, 1.31] |
| 1.75.1 People with use of statins | 0 | 0 | Risk Ratio (M‐H, Fixed, 95% CI) | Not estimable |
| 1.75.2 People without use of statins | 0 | 0 | Risk Ratio (M‐H, Fixed, 95% CI) | Not estimable |
| 1.75.3 Mixed | 2 | 4520 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.08 [0.90, 1.31] |
| 1.76 Sudden cardiac death according to the mean age Show forest plot | 2 | 4520 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.08 [0.90, 1.31] |
| 1.76.1 18 to 59 years | 0 | 0 | Risk Ratio (M‐H, Fixed, 95% CI) | Not estimable |
| 1.76.2 60 and above | 2 | 4520 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.08 [0.90, 1.31] |
| 1.77 Sudden cardiac death according to length of follow‐up Show forest plot | 2 | 4520 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.08 [0.90, 1.31] |
| 1.77.1 Trials with less than 12 months follow‐up | 0 | 0 | Risk Ratio (M‐H, Fixed, 95% CI) | Not estimable |
| 1.77.2 Trials with equal to or longer than 12 months follow‐up | 2 | 4520 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.08 [0.90, 1.31] |
| 1.78 Sudden cardiac death according to class of antibiotic Show forest plot | 2 | 4520 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.08 [0.90, 1.31] |
| 1.78.1 Macrolide | 2 | 4520 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.08 [0.90, 1.31] |
| 1.78.2 Tetracycline | 0 | 0 | Risk Ratio (M‐H, Fixed, 95% CI) | Not estimable |
| 1.78.3 Quinolone | 0 | 0 | Risk Ratio (M‐H, Fixed, 95% CI) | Not estimable |
| 1.79 Sudden cardiac death according to control intervention Show forest plot | 2 | 4520 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.08 [0.90, 1.31] |
| 1.79.1 Placebo‐controlled trials | 2 | 4520 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.08 [0.90, 1.31] |
| 1.79.2 No control intervention | 0 | 0 | Risk Ratio (M‐H, Fixed, 95% CI) | Not estimable |
| 1.80 HOSPITALISATION FOR ANY CAUSE Show forest plot | 7 | 18615 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.04 [0.91, 1.19] |
| 1.81 REVASCULARISATION Show forest plot | 11 | 19631 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.98 [0.91, 1.05] |
| 1.82 UNSTABLE ANGINA PECTORIS Show forest plot | 9 | 22172 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.02 [0.92, 1.12] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 2.1 ALL‐CAUSE MORTALITY Show forest plot | 6 | 9517 | Risk Ratio (M‐H, Random, 95% CI) | 1.25 [1.06, 1.48] |
| 2.2 All‐cause mortality ‐ trials at low risk of bias Show forest plot | 2 | 4674 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.25 [1.03, 1.51] |
| 2.3 All‐cause mortality ‐ 'best‐worst case' scenario Show forest plot | 6 | 9518 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.22 [1.03, 1.43] |
| 2.4 All‐cause mortality ‐ 'worst‐best case' scenario Show forest plot | 6 | 9518 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.31 [1.11, 1.54] |
| 2.5 All‐cause mortality ‐ modified 'best‐worst case' scenario Show forest plot | 6 | 9518 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.24 [1.05, 1.46] |
| 2.6 All‐cause mortality ‐ modified 'worst‐best case' scenario Show forest plot | 6 | 9518 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.28 [1.09, 1.51] |
| 2.7 All‐cause mortality ‐ trials with optimal medical therapy Show forest plot | 3 | 8682 | Risk Ratio (M‐H, Random, 95% CI) | 1.27 [1.07, 1.50] |
| 2.8 All‐cause mortality according to type of antibiotic Show forest plot | 6 | 9517 | Risk Ratio (M‐H, Random, 95% CI) | 1.25 [1.06, 1.48] |
| 2.8.1 Azithromycin | 2 | 362 | Risk Ratio (M‐H, Random, 95% CI) | 1.07 [0.33, 3.43] |
| 2.8.2 Clarithromycin | 3 | 4993 | Risk Ratio (M‐H, Random, 95% CI) | 1.25 [1.04, 1.51] |
| 2.8.3 Gatifloxacin | 1 | 4162 | Risk Ratio (M‐H, Random, 95% CI) | 1.29 [0.89, 1.85] |
| 2.9 All‐cause mortality according to antibody status Show forest plot | 6 | 9517 | Risk Ratio (M‐H, Random, 95% CI) | 1.25 [1.06, 1.48] |
| 2.9.1 People with antibodies | 2 | 362 | Risk Ratio (M‐H, Random, 95% CI) | 1.07 [0.33, 3.43] |
| 2.9.2 People without antibodies | 0 | 0 | Risk Ratio (M‐H, Random, 95% CI) | Not estimable |
| 2.9.3 Mixed | 4 | 9155 | Risk Ratio (M‐H, Random, 95% CI) | 1.26 [1.07, 1.49] |
| 2.10 All‐cause mortality according to use of statins Show forest plot | 4 | 9155 | Risk Ratio (M‐H, Random, 95% CI) | 1.26 [1.07, 1.49] |
| 2.10.1 People with use of statins | 1 | 4162 | Risk Ratio (M‐H, Random, 95% CI) | 1.29 [0.89, 1.85] |
| 2.10.2 People without use of statins | 0 | 0 | Risk Ratio (M‐H, Random, 95% CI) | Not estimable |
| 2.10.3 Mixed | 3 | 4993 | Risk Ratio (M‐H, Random, 95% CI) | 1.25 [1.04, 1.51] |
| 2.11 All‐cause mortality according to the mean age Show forest plot | 6 | 9517 | Risk Ratio (M‐H, Random, 95% CI) | 1.25 [1.06, 1.48] |
| 2.11.1 18 to 59 years | 2 | 4222 | Risk Ratio (M‐H, Random, 95% CI) | 1.26 [0.88, 1.82] |
| 2.11.2 60 and above | 4 | 5295 | Risk Ratio (M‐H, Random, 95% CI) | 1.25 [1.04, 1.51] |
| 2.12 All‐cause mortality according to clinical trial registration status Show forest plot | 6 | 9517 | Risk Ratio (M‐H, Random, 95% CI) | 1.25 [1.06, 1.48] |
| 2.12.1 Pre‐registration | 2 | 8534 | Risk Ratio (M‐H, Random, 95% CI) | 1.26 [1.06, 1.49] |
| 2.12.2 Post‐registration | 0 | 0 | Risk Ratio (M‐H, Random, 95% CI) | Not estimable |
| 2.12.3 No registration | 4 | 983 | Risk Ratio (M‐H, Random, 95% CI) | 1.23 [0.63, 2.40] |
| 2.13 All‐cause mortality according to class of antibiotic Show forest plot | 6 | 9517 | Risk Ratio (M‐H, Random, 95% CI) | 1.25 [1.06, 1.48] |
| 2.13.1 Macrolides | 5 | 5355 | Risk Ratio (M‐H, Random, 95% CI) | 1.25 [1.04, 1.50] |
| 2.13.2 Tetracycline | 0 | 0 | Risk Ratio (M‐H, Random, 95% CI) | Not estimable |
| 2.13.3 Quinolone | 1 | 4162 | Risk Ratio (M‐H, Random, 95% CI) | 1.29 [0.89, 1.85] |
| 2.14 All‐cause mortality according to funding Show forest plot | 6 | 9517 | Risk Ratio (M‐H, Random, 95% CI) | 1.25 [1.06, 1.48] |
| 2.14.1 Industry funded or unknown funded trials | 3 | 4783 | Risk Ratio (M‐H, Random, 95% CI) | 1.29 [0.93, 1.80] |
| 2.14.2 Non‐industry funded trials | 3 | 4734 | Risk Ratio (M‐H, Random, 95% CI) | 1.24 [1.03, 1.50] |
| 2.15 All‐cause mortality according to control intervention Show forest plot | 6 | 9517 | Risk Ratio (M‐H, Random, 95% CI) | 1.25 [1.06, 1.48] |
| 2.15.1 Placebo‐controlled trials | 6 | 9517 | Risk Ratio (M‐H, Random, 95% CI) | 1.25 [1.06, 1.48] |
| 2.15.2 No control intervention | 0 | 0 | Risk Ratio (M‐H, Random, 95% CI) | Not estimable |
| 2.16 CARDIOVASCULAR MORTALITY Show forest plot | 5 | 9044 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.50 [1.17, 1.91] |
| 2.17 Cardiovascular mortality ‐ trials at low risk of bias Show forest plot | 2 | 4674 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.43 [1.09, 1.89] |
| 2.18 Cardiovascular mortality ‐ 'best‐worst case' scenario Show forest plot | 5 | 9045 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.39 [1.09, 1.77] |
| 2.19 Cardiovascular mortality ‐ 'worst‐best case' scenario Show forest plot | 5 | 9045 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.60 [1.26, 2.04] |
| 2.20 Cardiovascular mortality ‐ modified 'best‐worst case' scenario Show forest plot | 5 | 9045 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.44 [1.13, 1.84] |
| 2.21 Cardiovascular mortality ‐ modified 'worst‐best case' scenario Show forest plot | 5 | 9045 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.56 [1.22, 1.98] |
| 2.22 Cardiovascular mortality ‐ trials with optimal medical therapy Show forest plot | 3 | 8682 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.52 [1.18, 1.95] |
| 2.23 Cardiovascular mortality according to type of antibiotic Show forest plot | 5 | 9044 | Risk Ratio (M‐H, Random, 95% CI) | 1.48 [1.15, 1.89] |
| 2.23.1 Azithromycin | 2 | 362 | Risk Ratio (M‐H, Random, 95% CI) | 1.07 [0.33, 3.43] |
| 2.23.2 Clarithromycin | 2 | 4520 | Risk Ratio (M‐H, Random, 95% CI) | 2.00 [0.50, 7.94] |
| 2.23.3 Gatifloxacin | 1 | 4162 | Risk Ratio (M‐H, Random, 95% CI) | 1.64 [0.93, 2.89] |
| 2.24 Cardiovascular mortality according to antibody status Show forest plot | 5 | 9044 | Risk Ratio (M‐H, Random, 95% CI) | 1.48 [1.15, 1.89] |
| 2.24.1 People with antibodies | 2 | 362 | Risk Ratio (M‐H, Random, 95% CI) | 1.07 [0.33, 3.43] |
| 2.24.2 People without antibodies | 0 | 0 | Risk Ratio (M‐H, Random, 95% CI) | Not estimable |
| 2.24.3 Mixed | 3 | 8682 | Risk Ratio (M‐H, Random, 95% CI) | 1.50 [1.16, 1.93] |
| 2.25 Cardiovascular mortality according to use of statins Show forest plot | 3 | 8682 | Risk Ratio (M‐H, Random, 95% CI) | 1.50 [1.16, 1.93] |
| 2.25.1 People with use of statins | 1 | 4162 | Risk Ratio (M‐H, Random, 95% CI) | 1.64 [0.93, 2.89] |
| 2.25.2 People without use of statins | 0 | 0 | Risk Ratio (M‐H, Random, 95% CI) | Not estimable |
| 2.25.3 Mixed | 2 | 4520 | Risk Ratio (M‐H, Random, 95% CI) | 2.00 [0.50, 7.94] |
| 2.26 Cardiovascular mortality according to the mean age Show forest plot | 5 | 9044 | Risk Ratio (M‐H, Random, 95% CI) | 1.48 [1.15, 1.89] |
| 2.26.1 18 to 59 years | 2 | 4222 | Risk Ratio (M‐H, Random, 95% CI) | 1.56 [0.89, 2.72] |
| 2.26.2 60 and above | 3 | 4822 | Risk Ratio (M‐H, Random, 95% CI) | 1.46 [1.11, 1.92] |
| 2.27 Cardiovascular mortality according to clinical trial registration status Show forest plot | 5 | 9044 | Risk Ratio (M‐H, Random, 95% CI) | 1.48 [1.15, 1.89] |
| 2.27.1 Pre‐registration | 2 | 8534 | Risk Ratio (M‐H, Random, 95% CI) | 1.48 [1.15, 1.91] |
| 2.27.2 Post‐registration | 0 | 0 | Risk Ratio (M‐H, Random, 95% CI) | Not estimable |
| 2.27.3 No registration | 3 | 510 | Risk Ratio (M‐H, Random, 95% CI) | 1.48 [0.43, 5.10] |
| 2.28 Cardiovascular mortality according to class of antibiotic Show forest plot | 5 | 9044 | Risk Ratio (M‐H, Random, 95% CI) | 1.48 [1.15, 1.89] |
| 2.28.1 Macrolides | 4 | 4882 | Risk Ratio (M‐H, Random, 95% CI) | 1.44 [1.10, 1.90] |
| 2.28.2 Tetracycline | 0 | 0 | Risk Ratio (M‐H, Random, 95% CI) | Not estimable |
| 2.28.3 Quinolone | 1 | 4162 | Risk Ratio (M‐H, Random, 95% CI) | 1.64 [0.93, 2.89] |
| 2.29 Cardiovascular mortality according to funding Show forest plot | 5 | 9044 | Risk Ratio (M‐H, Random, 95% CI) | 1.48 [1.15, 1.89] |
| 2.29.1 Industry funded or unknown funded trials | 2 | 4310 | Risk Ratio (M‐H, Random, 95% CI) | 2.09 [0.64, 6.82] |
| 2.29.2 Non‐industry funded trials | 3 | 4734 | Risk Ratio (M‐H, Random, 95% CI) | 1.42 [1.08, 1.87] |
| 2.30 Cardiovascular mortality according to control intervention Show forest plot | 5 | 9044 | Risk Ratio (M‐H, Random, 95% CI) | 1.48 [1.15, 1.89] |
| 2.30.1 Placebo‐controlled trials | 5 | 9044 | Risk Ratio (M‐H, Random, 95% CI) | 1.48 [1.15, 1.89] |
| 2.30.2 No control intervention | 0 | 0 | Risk Ratio (M‐H, Random, 95% CI) | Not estimable |
| 2.31 MYOCARDIAL INFARCTION Show forest plot | 5 | 9457 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.95 [0.82, 1.11] |
| 2.32 Myocardial infarction ‐ trials at low risk of bias Show forest plot | 2 | 4674 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.08 [0.87, 1.33] |
| 2.33 Myocardial infarction ‐ 'best‐worst case' scenario Show forest plot | 5 | 9458 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.93 [0.80, 1.08] |
| 2.34 Myocardial infarction ‐ 'worst‐best case' scenario Show forest plot | 5 | 9458 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.99 [0.85, 1.15] |
| 2.35 Myocardial infarction ‐ modified 'best‐worst case' scenario Show forest plot | 5 | 9458 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.94 [0.81, 1.09] |
| 2.36 Myocardial infarction ‐ modified 'worst‐best case' scenario Show forest plot | 5 | 9458 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.97 [0.84, 1.13] |
| 2.37 Myocardial infarction ‐ trials with optimal medical therapy Show forest plot | 3 | 8682 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.96 [0.83, 1.12] |
| 2.38 Myocardial infarction according to type of antibiotic Show forest plot | 5 | 9457 | Risk Ratio (M‐H, Random, 95% CI) | 0.89 [0.68, 1.17] |
| 2.38.1 Azithromycin | 1 | 302 | Risk Ratio (M‐H, Random, 95% CI) | 0.68 [0.19, 2.35] |
| 2.38.2 Clarithromycin | 3 | 4993 | Risk Ratio (M‐H, Random, 95% CI) | 0.64 [0.25, 1.63] |
| 2.38.3 Gatifloxacin | 1 | 4162 | Risk Ratio (M‐H, Random, 95% CI) | 0.89 [0.72, 1.12] |
| 2.39 Myocardial infarction according to antibody status Show forest plot | 5 | 9457 | Risk Ratio (M‐H, Random, 95% CI) | 0.89 [0.68, 1.17] |
| 2.39.1 People with antibodies | 1 | 302 | Risk Ratio (M‐H, Random, 95% CI) | 0.68 [0.19, 2.35] |
| 2.39.2 People without antibodies | 0 | 0 | Risk Ratio (M‐H, Random, 95% CI) | Not estimable |
| 2.39.3 Mixed | 4 | 9155 | Risk Ratio (M‐H, Random, 95% CI) | 0.89 [0.65, 1.21] |
| 2.40 Myocardial infarction according to use of statins Show forest plot | 5 | 9457 | Risk Ratio (M‐H, Random, 95% CI) | 0.89 [0.68, 1.17] |
| 2.40.1 People with use of statins | 1 | 4162 | Risk Ratio (M‐H, Random, 95% CI) | 0.89 [0.72, 1.12] |
| 2.40.2 People without use of statins | 0 | 0 | Risk Ratio (M‐H, Random, 95% CI) | Not estimable |
| 2.40.3 Mixed | 4 | 5295 | Risk Ratio (M‐H, Random, 95% CI) | 0.69 [0.35, 1.36] |
| 2.41 Myocardial infarction according to the mean age Show forest plot | 5 | 9457 | Risk Ratio (M‐H, Random, 95% CI) | 0.89 [0.68, 1.17] |
| 2.41.1 18 to 59 years | 1 | 4162 | Risk Ratio (M‐H, Random, 95% CI) | 0.89 [0.72, 1.12] |
| 2.41.2 60 and above | 4 | 5295 | Risk Ratio (M‐H, Random, 95% CI) | 0.69 [0.35, 1.36] |
| 2.42 Myocardial infarction according to clinical trial registration status Show forest plot | 5 | 9457 | Risk Ratio (M‐H, Random, 95% CI) | 0.89 [0.68, 1.17] |
| 2.42.1 Pre‐registration | 2 | 8534 | Risk Ratio (M‐H, Random, 95% CI) | 0.99 [0.81, 1.21] |
| 2.42.2 Post‐registration | 0 | 0 | Risk Ratio (M‐H, Random, 95% CI) | Not estimable |
| 2.42.3 No registration | 3 | 923 | Risk Ratio (M‐H, Random, 95% CI) | 0.44 [0.21, 0.91] |
| 2.43 Myocardial infarction according to class of antibiotic Show forest plot | 5 | 9457 | Risk Ratio (M‐H, Random, 95% CI) | 0.89 [0.68, 1.17] |
| 2.43.1 Macrolide | 4 | 5295 | Risk Ratio (M‐H, Random, 95% CI) | 0.69 [0.35, 1.36] |
| 2.43.2 Tetracycline | 0 | 0 | Risk Ratio (M‐H, Random, 95% CI) | Not estimable |
| 2.43.3 Quinolone | 1 | 4162 | Risk Ratio (M‐H, Random, 95% CI) | 0.89 [0.72, 1.12] |
| 2.44 Myocardial infarction according to funding Show forest plot | 5 | 9457 | Risk Ratio (M‐H, Random, 95% CI) | 0.89 [0.68, 1.17] |
| 2.44.1 Industry funded or unknown funded trials | 3 | 4783 | Risk Ratio (M‐H, Random, 95% CI) | 0.62 [0.30, 1.28] |
| 2.44.2 Non‐industry funded trials | 2 | 4674 | Risk Ratio (M‐H, Random, 95% CI) | 1.08 [0.87, 1.34] |
| 2.45 Myocardial infarction according to control intervention Show forest plot | 5 | 9457 | Risk Ratio (M‐H, Random, 95% CI) | 0.89 [0.68, 1.17] |
| 2.45.1 Placebo‐controlled trials | 5 | 9457 | Risk Ratio (M‐H, Random, 95% CI) | 0.89 [0.68, 1.17] |
| 2.45.2 No control intervention | 0 | 0 | Risk Ratio (M‐H, Random, 95% CI) | Not estimable |
| 2.46 STROKE Show forest plot | 5 | 9457 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.17 [0.90, 1.52] |
| 2.47 Stroke ‐ trials at low risk of bias Show forest plot | 2 | 4674 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.17 [0.86, 1.60] |
| 2.48 Stroke ‐ 'best‐worst case' scenario Show forest plot | 5 | 9458 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.08 [0.84, 1.40] |
| 2.49 Stroke ‐ 'worst‐best case' scenario Show forest plot | 5 | 9458 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.28 [0.99, 1.66] |
| 2.50 Stroke ‐ modified 'best‐worst case' scenario Show forest plot | 5 | 9458 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.13 [0.87, 1.46] |
| 2.51 Stroke ‐ modified 'worst‐best case' scenario Show forest plot | 5 | 9458 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.23 [0.95, 1.60] |
| 2.52 Stroke ‐ trials with optimal medical therapy Show forest plot | 3 | 8682 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.16 [0.88, 1.53] |
| 2.53 Stroke according to type of antibiotic Show forest plot | 5 | 9457 | Risk Ratio (M‐H, Random, 95% CI) | 1.17 [0.90, 1.53] |
| 2.53.1 Azithromycin | 1 | 302 | Risk Ratio (M‐H, Random, 95% CI) | 0.34 [0.04, 3.21] |
| 2.53.2 Clarithromycin | 3 | 4993 | Risk Ratio (M‐H, Random, 95% CI) | 1.24 [0.92, 1.67] |
| 2.53.3 Gatifloxacin | 1 | 4162 | Risk Ratio (M‐H, Random, 95% CI) | 1.05 [0.59, 1.88] |
| 2.54 Stroke according to antibody status Show forest plot | 5 | 9457 | Risk Ratio (M‐H, Random, 95% CI) | 1.17 [0.90, 1.53] |
| 2.54.1 People with antibodies | 1 | 302 | Risk Ratio (M‐H, Random, 95% CI) | 0.34 [0.04, 3.21] |
| 2.54.2 People without antibodies | 0 | 0 | Risk Ratio (M‐H, Random, 95% CI) | Not estimable |
| 2.54.3 Mixed | 4 | 9155 | Risk Ratio (M‐H, Random, 95% CI) | 1.20 [0.92, 1.56] |
| 2.55 Stroke according to use of statins Show forest plot | 5 | 9457 | Risk Ratio (M‐H, Random, 95% CI) | 1.17 [0.90, 1.53] |
| 2.55.1 People with use of statins | 1 | 4162 | Risk Ratio (M‐H, Random, 95% CI) | 1.05 [0.59, 1.88] |
| 2.55.2 People without use of statins | 0 | 0 | Risk Ratio (M‐H, Random, 95% CI) | Not estimable |
| 2.55.3 Mixed | 4 | 5295 | Risk Ratio (M‐H, Random, 95% CI) | 1.21 [0.90, 1.63] |
| 2.56 Stroke according to the mean age Show forest plot | 5 | 9453 | Risk Ratio (M‐H, Random, 95% CI) | 1.17 [0.90, 1.53] |
| 2.56.1 18 to 59 years | 1 | 4162 | Risk Ratio (M‐H, Random, 95% CI) | 1.05 [0.59, 1.88] |
| 2.56.2 60 and above | 4 | 5291 | Risk Ratio (M‐H, Random, 95% CI) | 1.21 [0.90, 1.63] |
| 2.57 Stroke according to clinical trial registration status Show forest plot | 5 | 9457 | Risk Ratio (M‐H, Random, 95% CI) | 1.17 [0.90, 1.53] |
| 2.57.1 Pre‐registration | 2 | 8534 | Risk Ratio (M‐H, Random, 95% CI) | 1.17 [0.88, 1.54] |
| 2.57.2 Post‐registration | 0 | 0 | Risk Ratio (M‐H, Random, 95% CI) | Not estimable |
| 2.57.3 No registration | 3 | 923 | Risk Ratio (M‐H, Random, 95% CI) | 1.24 [0.52, 2.95] |
| 2.58 Stroke according to class of antibiotic Show forest plot | 5 | 9457 | Risk Ratio (M‐H, Random, 95% CI) | 1.17 [0.90, 1.53] |
| 2.58.1 Macrolide | 4 | 5295 | Risk Ratio (M‐H, Random, 95% CI) | 1.21 [0.90, 1.63] |
| 2.58.2 Tetracycline | 0 | 0 | Risk Ratio (M‐H, Random, 95% CI) | Not estimable |
| 2.58.3 Quinolone | 1 | 4162 | Risk Ratio (M‐H, Random, 95% CI) | 1.05 [0.59, 1.88] |
| 2.59 Stroke according to funding Show forest plot | 5 | 9457 | Risk Ratio (M‐H, Random, 95% CI) | 1.17 [0.90, 1.53] |
| 2.59.1 Industry funded or unknown funded trials | 3 | 4783 | Risk Ratio (M‐H, Random, 95% CI) | 1.17 [0.71, 1.92] |
| 2.59.2 Non‐industry funded trials | 2 | 4674 | Risk Ratio (M‐H, Random, 95% CI) | 1.06 [0.50, 2.25] |
| 2.60 Stroke according to control intervention Show forest plot | 5 | 9457 | Risk Ratio (M‐H, Random, 95% CI) | 1.17 [0.90, 1.53] |
| 2.60.1 Placebo‐controlled trials | 5 | 9457 | Risk Ratio (M‐H, Random, 95% CI) | 1.17 [0.90, 1.53] |
| 2.60.2 No control intervention | 0 | 0 | Risk Ratio (M‐H, Random, 95% CI) | Not estimable |
| 2.61 SUDDEN CARDIAC DEATH Show forest plot | 2 | 4520 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.77 [1.28, 2.44] |
| 2.62 Sudden cardiac death ‐ trials at low risk of bias Show forest plot | 1 | 4372 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.75 [1.27, 2.42] |
| 2.63 Sudden cardiac death ‐ 'best‐worst case' scenario Show forest plot | 2 | 4521 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.68 [1.22, 2.30] |
| 2.64 Sudden cardiac death ‐ 'worst‐best case' scenario Show forest plot | 2 | 4521 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.91 [1.39, 2.62] |
| 2.65 Sudden cardiac death ‐ modified 'best‐worst case' scenario Show forest plot | 2 | 4521 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.74 [1.26, 2.39] |
| 2.66 Sudden cardiac death ‐ modified 'worst‐best case' scenario Show forest plot | 2 | 4521 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.84 [1.34, 2.53] |
| 2.67 Sudden cardiac death according to clinical trial registration status Show forest plot | 2 | 4520 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.77 [1.28, 2.44] |
| 2.67.1 Pre‐registration | 1 | 4372 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.75 [1.27, 2.42] |
| 2.67.2 Post‐registration | 0 | 0 | Risk Ratio (M‐H, Fixed, 95% CI) | Not estimable |
| 2.67.3 No registration | 1 | 148 | Risk Ratio (M‐H, Fixed, 95% CI) | 3.00 [0.12, 72.47] |
| 2.68 Sudden cardiac death according to funding Show forest plot | 2 | 4520 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.77 [1.28, 2.44] |
| 2.68.1 Industry funded or unknown funded trials | 1 | 148 | Risk Ratio (M‐H, Fixed, 95% CI) | 3.00 [0.12, 72.47] |
| 2.68.2 Non‐industry funded trials | 1 | 4372 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.75 [1.27, 2.42] |
| 2.69 Sudden cardiac death according to type of antibiotic Show forest plot | 2 | 4520 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.77 [1.28, 2.44] |
| 2.69.1 Clarithromycin | 2 | 4520 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.77 [1.28, 2.44] |
| 2.70 Sudden cardiac death according to antibody status Show forest plot | 2 | 4520 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.77 [1.28, 2.44] |
| 2.70.1 People with antibodies | 0 | 0 | Risk Ratio (M‐H, Fixed, 95% CI) | Not estimable |
| 2.70.2 People without antibodies | 0 | 0 | Risk Ratio (M‐H, Fixed, 95% CI) | Not estimable |
| 2.70.3 Mixed | 2 | 4520 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.77 [1.28, 2.44] |
| 2.71 Sudden cardiac death according to use of statins Show forest plot | 2 | 4520 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.77 [1.28, 2.44] |
| 2.71.1 People with use of statins | 0 | 0 | Risk Ratio (M‐H, Fixed, 95% CI) | Not estimable |
| 2.71.2 People without use of statins | 0 | 0 | Risk Ratio (M‐H, Fixed, 95% CI) | Not estimable |
| 2.71.3 Mixed | 2 | 4520 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.77 [1.28, 2.44] |
| 2.72 Sudden cardiac death according to the mean age Show forest plot | 2 | 4520 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.77 [1.28, 2.44] |
| 2.72.1 18 to 59 years | 0 | 0 | Risk Ratio (M‐H, Fixed, 95% CI) | Not estimable |
| 2.72.2 60 and above | 2 | 4520 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.77 [1.28, 2.44] |
| 2.73 Sudden cardiac death according to class of antibiotic Show forest plot | 2 | 4520 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.77 [1.28, 2.44] |
| 2.73.1 Macrolide | 2 | 4520 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.77 [1.28, 2.44] |
| 2.73.2 Tetracycline | 0 | 0 | Risk Ratio (M‐H, Fixed, 95% CI) | Not estimable |
| 2.73.3 Quinolone | 0 | 0 | Risk Ratio (M‐H, Fixed, 95% CI) | Not estimable |
| 2.74 Sudden cardiac death according to control intervention Show forest plot | 2 | 4520 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.77 [1.28, 2.44] |
| 2.74.1 Placebo‐controlled trials | 2 | 4520 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.77 [1.28, 2.44] |
| 2.74.2 No control intervention | 0 | 0 | Risk Ratio (M‐H, Fixed, 95% CI) | Not estimable |
| 2.75 HOSPITALISATION FOR ANY CAUSE Show forest plot | 2 | 4464 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.03 [0.78, 1.34] |
| 2.76 REVASCULARISATION Show forest plot | 3 | 4937 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.94 [0.83, 1.07] |
| 2.77 UNSTABLE ANGINA PECTORIS Show forest plot | 4 | 5085 | Risk Ratio (M‐H, Random, 95% CI) | 0.96 [0.75, 1.23] |
