Effect of early treatment with anti‐hypertensive drugs on short and long‐term mortality in patients with an acute cardiovascular event

Marco I Perez; Vijaya M Musini; James M Wright

doi:10.1002/14651858.CD006743.pub2

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Figure 1

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Figure 2

Methodological quality graph: review authors' judgements about each methodological quality item presented as percentages across all included studies.

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Figure 3

Methodological quality summary: review authors' judgements about each methodological quality item for each included study.

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Figure 4

Forest plot of comparison: 4 Nitrates, outcome: 4.1 All‐cause mortality at 2 days.

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Figure 5

Forest plot of comparison: 4 Nitrates, outcome: 4.2 All‐cause mortality at 10 days.

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Figure 6

Forest plot of comparison: 4 Nitrates, outcome: 4.3 All‐cause mortality at ≥30 days.

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Figure 7

Forest plot of comparison: 1 ACEi, outcome: 1.1 All‐cause mortality at 2 days.

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Figure 8

Forest plot of comparison: 1 ACEi, outcome: 1.2 All‐cause mortality at 10 days.

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Figure 9

Forest plot of comparison: 2 BB, outcome: 2.1 All‐cause mortality at 2 days.

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Figure 10

Forest plot of comparison: 2 BB, outcome: 2.3 All‐cause mortality at 10 days.

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Figure 11

Forest plot of comparison: 2 BB, outcome: 2.4 All‐cause mortality at ≥30 day.

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Figure 12

Forest plot of comparison: 3 CCB, outcome: 3.1 All‐cause mortality at 2 days.

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Figure 13

Forest plot of comparison: 3 CCB, outcome: 3.2 All‐cause mortality at 10 days.

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Figure 14

Forest plot of comparison: 2 BB, outcome: 2.4 Weighted mean change in Systolic Blood pressure during first 24 hours.

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Figure 15

Forest plot of comparison: 2 BB, outcome: 2.5 Weighted mean change in Diastolic Blood pressure during first 24 hours.

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Figure 16

Forest plot of comparison: 2 BB, outcome: 2.6 Weighted mean change in heart rate during first 24 hours.

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Figure 17

Forest plot of comparison: 3 CCB, outcome: 3.6 Weighted mean change in heart rate during first 24 hours.

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Figure 18

Forest plot of comparison: 4 Nitrates, outcome: 4.4 Weighted mean change in Systolic Blood pressure during first 24 hours.

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Figure 19

Forest plot of comparison: 4 Nitrates, outcome: 4.8 Sensitivity analysis mortality 0‐2 vs. 3‐10 days vs. day 11 to end of treatment (35‐42 days).

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Figure 20

Forest plot of comparison: 1 ACEi, outcome: 1.7 Sensitivity analysis: mortality 0‐2 vs. 3‐10 days vs day 11 to end of treatment (35‐42 days).

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Analysis 1.1

Comparison 1 Nitrates, Outcome 1 All‐cause mortality at 2 days.

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Analysis 1.2

Comparison 1 Nitrates, Outcome 2 All‐cause mortality at 10 days.

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Analysis 1.3

Comparison 1 Nitrates, Outcome 3 All‐cause mortality at ≥30 days.

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Analysis 1.4

Comparison 1 Nitrates, Outcome 4 Weighted mean change in Systolic Blood pressure during first 24 hours.

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Analysis 1.5

Comparison 1 Nitrates, Outcome 5 Weighted mean change in Diastolic Blood pressure during first 24 hours.

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Analysis 1.6

Comparison 1 Nitrates, Outcome 6 Weighted mean change in heart rate during first 24 hours.

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Analysis 1.7

Comparison 1 Nitrates, Outcome 7 Sensitivity analysis mortality 0‐2 vs. 3‐10 days vs. day 11 to end of treatment (35‐42 days).

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Analysis 2.1

Comparison 2 ACEi, Outcome 1 All‐cause mortality at 2 days.

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Analysis 2.2

Comparison 2 ACEi, Outcome 2 All‐cause mortality at 10 days.

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Analysis 2.3

Comparison 2 ACEi, Outcome 3 Sensitivity analysis: mortality 0‐2 vs. 3‐10 days vs day 11 to end of treatment (35‐42 days).

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Analysis 3.1

Comparison 3 BB, Outcome 1 All‐cause mortality at 2 days.

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Analysis 3.2

Comparison 3 BB, Outcome 2 All‐cause mortality at 10 days.

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Analysis 3.3

Comparison 3 BB, Outcome 3 All‐cause mortality at ≥30 day.

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Analysis 3.4

Comparison 3 BB, Outcome 4 Weighted mean change in Systolic Blood pressure during first 24 hours.

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Analysis 3.5

Comparison 3 BB, Outcome 5 Weighted mean change in Diastolic Blood pressure during first 24 hours.

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Analysis 3.6

Comparison 3 BB, Outcome 6 Weighted mean change in heart rate during first 24 hours.

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Analysis 3.7

Comparison 3 BB, Outcome 7 Sensitivity analysis: mortality at 2 days, according to trial design.

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Analysis 4.1

Comparison 4 CCB, Outcome 1 All‐cause mortality at 2 days.

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Analysis 4.2

Comparison 4 CCB, Outcome 2 All‐cause mortality at 10 days.

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Analysis 4.3

Comparison 4 CCB, Outcome 3 All‐cause mortality at ≥30 days.

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Analysis 4.4

Comparison 4 CCB, Outcome 4 Weighted mean change in Systolic Blood pressure during first 24 hours.

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Analysis 4.5

Comparison 4 CCB, Outcome 5 Weighted mean change in Diastolic Blood pressure during first 24 hours.

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Analysis 4.6

Comparison 4 CCB, Outcome 6 Weighted mean change in heart rate during first 24 hours.

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Analysis 4.7

Comparison 4 CCB, Outcome 7 Sensititity analysis: mortality at 10 days, according underlying CVE.

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Analysis 4.8

Comparison 4 CCB, Outcome 8 Sensitivity Analysis: mortality at 10 days, according sub‐class of CCB in AMI.

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Summary of findings for the main comparison. Immediate and short term administration of nitrates in patients with acute cardiovascular events

Immediate and short term administration of nitrates in patients with acute cardiovascular events
Patient or population: patients with acute myocardial infarction¹ Settings: hospitalized within 24 hours of the symptom onset Intervention: Nitrates Comparison: Placebo or no treatment
Outcomes	*Illustrative comparative risks (95% CI)**		Relative effect (95% CI)	No of Participants (studies)	Quality of the evidence (GRADE)	Comments
	Assumed risk	Corresponding risk
	Placebo or no treatment	Nitrates
All‐cause mortality at 2 days ‐ immediate treatment Follow‐up: 0‐48 hours	Low risk population²		RR 0.81 (0.74 to 0.89)	82624 (6 studies)	⊕⊕⊕⊕ high	Highly significant benefit was achieved. 125 or 250 patients, with high or low risk, need to be treated to prevent 1 death
	20 per 1000	16 per 1000 (15 to 18)
	High risk population²
	40 per 1000	32 per 1000 (30 to 36)
All‐cause mortality at 10 days‐ short‐term treatment Follow‐up: 0‐10 days	Low risk population²		RR 0.91 (0.86 to 0.97)	78178 (6 studies)	⊕⊕⊕⊕ high	Significant benefit is demonstrated, but this is the same absolute magnitude as day 2. Thus, likely reflects the mortality benefit at day 2.
	50 per 1000	46 per 1000 (43 to 49)
	High risk population²
	80 per 1000	73 per 1000 (69 to 78)
The basis for the assumed risk* (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (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 High quality: Further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: We are very uncertain about the estimate.
¹ Mortality results for this clinical condition, at the different times, and according to the different modalities of treatment (immediate and short term) displayed here, are considered the key points for this summary of findings table .The other results can be found in text. ² These low and high risk values were chosen based on the second lowest, and second highest risks in the control group of the included studies

Summary of findings for the main comparison. Immediate and short term administration of nitrates in patients with acute cardiovascular events

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Summary of findings 2. Immediate and short term administration of ACE inhibitors in patients with acute cardiovascular events

Immediate and short term administration of ACE inhibitors in patients with acute cardiovascular events
Patient or population: acute myocardial infarction¹ Settings: hospitalized within 24 hours of the symptom onset Intervention: ACE‐inhibitors Comparison: Placebo or no treatment
Outcomes	*Illustrative comparative risks (95% CI)**		Relative effect (95% CI)	No of Participants (studies)	Quality of the evidence (GRADE)	Comments
	Assumed risk	Corresponding risk
	Placebo or no treatment	ACE‐inhibitors
All‐cause mortality at 2 days ‐ immediate treatment Follow‐up: 0‐48 hours	Low risk population²		RR 0.91 (0.82 to 1)	77414 (3 studies)	⊕⊕⊕⊕ high	No statistically significant effect, but possible benefit.
	20 per 1000	18 per 1000 (16 to 20)
	High risk population²
	40 per 1000	36 per 1000 (33 to 40)
All‐cause mortality at 10 days ‐ short‐term treatment Follow‐up: 0‐10 days	Low risk population³		RR 0.93 (0.87 to 0.98)	84311 (10 studies)	⊕⊕⊕⊕ high	Significant benefit was achieved. 200 or 333 patients, with high or low risk, need to be treated for 10 days to prevent 1 death
	40 per 1000	37 per 1000 (35 to 39)
	High risk population³
	70 per 1000	65 per 1000 (61 to 69)
The basis for the assumed risk* (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (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 High quality: Further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: We are very uncertain about the estimate.
¹ Mortality results for this clinical condition, at the different times, and according to the different modalities of treatment (immediate and short term) displayed here, are considered the key points for this summary of findings table . The other results can be found in text. ² These low and high risk values were chosen based on the lowest and highest risks in the control group of these 3 included studies ³ These low and high risk values were chosen based on the second lowest, and second highest risks in the control group of the included studies

Summary of findings 2. Immediate and short term administration of ACE inhibitors in patients with acute cardiovascular events

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Summary of findings 3. Immediate and short term administration of Beta‐blockers in patients with acute cardiovascular events

Immediate and short term administration of Beta‐blockers in patients with acute cardiovascular events
Patient or population: patients with acute myocardial infarction¹ Settings: hospitalized within 24 hours of symptom onset Intervention: Beta‐blockers Comparison: Placebo or no treatment
Outcomes	*Illustrative comparative risks (95% CI)**		Relative effect (95% CI)	No of Participants (studies)	Quality of the evidence (GRADE)	Comments
	Assumed risk	Corresponding risk
	Placebo or no treatment	Beta‐blockers
All‐cause mortality at 2 days ‐ immediate treatment Follow‐up: 0‐48 hours	Medium risk population²		RR 0.95 (0.85 to 1.07)	68007 (6 studies)	⊕⊕⊝⊝ low^3,4	No statistically significant effect.<BR/>
	15 per 1000	14 per 1000 (13 to 16)
All‐cause mortality at 10 days ‐ short‐term treatment Follow‐up: 0‐10 days	Medium risk population⁵		RR 0.96 (0.91 to 1.02)	71457 (14 studies)	⊕⊕⊕⊕ high	No statistically significant effect.
	42 per 1000	40 per 1000 (38 to 43)
The basis for the assumed risk* (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (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 High quality: Further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: We are very uncertain about the estimate.
¹ Mortality results for this clinical condition, at the different times, and according to the different modalities of treatment (immediate and short term) displayed here, are considered the key points for this summary of findings table . The other results can be found in text ² Medium risk was chosen as there was little variation in the control group risk across included trials ³ Performance bias was highly suspected in a large open label‐trial ⁴ There was significant variability in the effect estimate ⁵ This is the medium control group risk from the included studies

Summary of findings 3. Immediate and short term administration of Beta‐blockers in patients with acute cardiovascular events

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Summary of findings 4. Immediate and short term administration of calcium channel blockers (CCB) in patients with acute cardiovascular events

Immediate and short term administration of calcium channel blockers (CCB) in patients with acute cardiovascular events
Patient or population: patients with acute myocardial infarction or stroke¹ Settings: hospitalized within 24 hours of the onset Intervention: CCB Comparison: Placebo or no treatment
Outcomes	*Illustrative comparative risks (95% CI)**		Relative effect (95% CI)	No of Participants (studies)	Quality of the evidence (GRADE)	Comments
	Assumed risk	Corresponding risk
	Placebo or no treatment	CCB
All‐cause mortality at 2 days ‐ immediate treatment Follow‐up: 0‐48 hours	Medium risk population²		RR 2.33 (0.62 to 8.78)	242 (3 studies)	⊕⊝⊝⊝ very low^3,4,5	No statistically significant effect. Not enough trials/patients or events.
	13 per 1000	30 per 1000 (8 to 114)
All‐cause mortality at 10 days ‐ short‐term treatment Follow‐up: 0‐10 days	Medium risk population⁶		RR 1.01 (0.73 to 1.38)	1900 (15 studies)	⊕⊝⊝⊝ very low^3,4,5	No statistically significant effect. Not enough trials/patients or events.
	70 per 1000	71 per 1000 (51 to 97)
The basis for the assumed risk* (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (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 High quality: Further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: We are very uncertain about the estimate.
¹ Mortality results for these clinical conditions, at the different times, and according to the different modalities of treatment (immediate and short term) displayed here, are considered the key points for this summary of findings table .The other results can be found in text ² Only the medium risk was chosen as there was little variation in the control group risk across included trials ³ These were very small open‐label trials ⁴ The 95 % confidence intervals of the effect estimate goes in opposite direction across trials reaching the threshold for clear benefit (RR=0.75) and clear harm (RR=1.25) ⁵ Probably there are many missing reports ⁶ This is the median control group risk from the included studies

Summary of findings 4. Immediate and short term administration of calcium channel blockers (CCB) in patients with acute cardiovascular events

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Table 1. Overview of the included trials according to treatment group

	Active drug	Placebo or No treatment
Participants in trials* involving (No.of trials):
ACE inhibitors(12)	42,260	42,196
B‐blockers(20)	36,338	36,262
CCB(18)	1,111	1,030
Nitrates(18)	42,206	42,207
All trials (65)^	83,234^	82,972^
Participants in trial design (No. of trials):
Double‐blind (40)	62,849(76%)	62,638(75%)
Not double‐blind (25)	20,385 (24%)	20,334 (25 %)
Weighted mean age (years) [trials / participants with data]	60.91 [49 / 43,243]	60.85 [49/ 43,000]
Weighted mean blood pressure (mm Hg) @ baseline [trials / participants with data]
Systolic	133.7 [34 / 41,862]	133.7 [34 / 41,669]
Diastolic	82.2 [25 / 7,125]	82.7 [25 / 7,043]
Female patients (%) [Based on trials reporting gender]	26% [47 / 82,342]	25% [47 / 82,036]
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* See below references of the randomized controlled trials for each row. ^ This total is less than the sum of all four categories as 2 trials (GSSI‐3, ISIS‐4) used 2x2 factorial design and one trial (Hargreaves 1992) compare drugs from two different categories of anti‐hypertensive with the same placebo or control group. The link to the references of the RCTs according to each row is as follow: ACEi (12 trials):Bussmann 1992, CONSENSUS‐II 1992, Di Pasquale 1994, Di Pasquale 1997, PRACTICAL 1994, Galcera 1993, GISSI‐3 1994, Hargreaves 1992, ISIS‐4 1995, Nabel 1991, Schulman 1995, Wagner 2002. B‐Blockers (20 trials): Clausen 1966, COMMIT 2005, Heber 1987, ICSG 1984, ISIS‐1 1986,Johannessen 1987; MIAMI 1985; MILIS 1984; Mitchell 2002; Norris 1978; Norris 1980; Norris 1984; Owensby 1985; Peter 1978; Salathia 1985; TIMI‐IIB 1991; Tonkin 1981; Van‐de 1993; von Essen 1982; Yusuf 1983. Calcium Channel Blockers (18 trials):Branagan 1986; Crea 1985; Eichler 1985; Erbel 1988; Marangelli 2000; Muller 1984; Natale 1999; Pimenta 1985; Pizzetti 2001; Sirnes 1984; Theroux 1998; Zannad 1988; Gelmers 1988; VENUS 2001; Infeld 1999; Limburg 1990; Paci 1989; INWEST 1994. Nitrates(18 trials):Beaufils 1988; Bussmann 1981; Charvat 1990; Chiche 1979; Cohn 1982; Durrer 1982; ESPRIM 1994; Fitzgerald 1990; Flaherty 1983; GISSI‐3 1994; Hargreaves 1992; Hildebrandt 1992; ISIS‐4 1995; Jaffe 1983; Jugdutt 1988; Jugdutt 1983; Lis 1984; Zharov 1991

Table 1. Overview of the included trials according to treatment group

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Comparison 1. Nitrates

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 All‐cause mortality at 2 days Show forest plot	6	82624	Risk Ratio (M‐H, Fixed, 95% CI)	0.81 [0.74, 0.89]

2 All‐cause mortality at 10 days Show forest plot	16	84185	Risk Ratio (M‐H, Fixed, 95% CI)	0.91 [0.86, 0.96]

2.1 immediate treatment	10	6007	Risk Ratio (M‐H, Fixed, 95% CI)	0.84 [0.69, 1.01]
2.2 short‐term treatment	6	78178	Risk Ratio (M‐H, Fixed, 95% CI)	0.91 [0.86, 0.97]
3 All‐cause mortality at ≥30 days Show forest plot	10	6341	Risk Ratio (M‐H, Fixed, 95% CI)	0.91 [0.81, 1.02]

3.1 immediate treatment	7	5771	Risk Ratio (M‐H, Fixed, 95% CI)	0.92 [0.82, 1.04]
3.2 short‐term treatment	3	570	Risk Ratio (M‐H, Fixed, 95% CI)	0.72 [0.48, 1.10]
4 Weighted mean change in Systolic Blood pressure during first 24 hours Show forest plot	7	1958	Mean Difference (IV, Fixed, 95% CI)	‐12.67 [‐14.51, ‐10.83]

5 Weighted mean change in Diastolic Blood pressure during first 24 hours Show forest plot	6	1146	Mean Difference (IV, Fixed, 95% CI)	‐7.50 [‐9.07, ‐5.93]

6 Weighted mean change in heart rate during first 24 hours Show forest plot	6	810	Mean Difference (IV, Fixed, 95% CI)	‐0.83 [‐2.83, 1.17]

7 Sensitivity analysis mortality 0‐2 vs. 3‐10 days vs. day 11 to end of treatment (35‐42 days) Show forest plot	2		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

7.1 mortality up to day 2	2	77368	Risk Ratio (M‐H, Fixed, 95% CI)	0.82 [0.74, 0.90]
7.2 mortality from day 3 to day 10	2	75792	Risk Ratio (M‐H, Fixed, 95% CI)	0.98 [0.91, 1.06]
7.3 mortality from day 11 to 35‐42 days	2	73319	Risk Ratio (M‐H, Fixed, 95% CI)	1.10 [1.00, 1.22]

Comparison 1. Nitrates

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Comparison 2. ACEi

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 All‐cause mortality at 2 days Show forest plot	3	77414	Risk Ratio (M‐H, Fixed, 95% CI)	0.91 [0.82, 1.00]

2 All‐cause mortality at 10 days Show forest plot	12	84456	Risk Ratio (M‐H, Fixed, 95% CI)	0.93 [0.87, 0.98]

2.1 immediate treatment	2	145	Risk Ratio (M‐H, Fixed, 95% CI)	0.68 [0.12, 3.98]
2.2 short‐term treatment	10	84311	Risk Ratio (M‐H, Fixed, 95% CI)	0.93 [0.87, 0.98]
3 Sensitivity analysis: mortality 0‐2 vs. 3‐10 days vs day 11 to end of treatment (35‐42 days) Show forest plot	2		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

3.1 mortality up to day 2	2	77368	Risk Ratio (M‐H, Fixed, 95% CI)	0.91 [0.82, 1.00]
3.2 mortality from 3 to 10 days	2	75792	Risk Ratio (M‐H, Fixed, 95% CI)	0.93 [0.86, 1.01]
3.3 mortality from 11 to 35‐42 days	2	73345	Risk Ratio (M‐H, Fixed, 95% CI)	0.93 [0.85, 1.03]

Comparison 2. ACEi

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Comparison 3. BB

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 All‐cause mortality at 2 days Show forest plot	6	68007	Risk Ratio (M‐H, Fixed, 95% CI)	0.95 [0.85, 1.07]

2 All‐cause mortality at 10 days Show forest plot	20	72600	Risk Ratio (M‐H, Fixed, 95% CI)	0.96 [0.91, 1.02]

2.1 immediate treatment	6	1143	Risk Ratio (M‐H, Fixed, 95% CI)	1.12 [0.60, 2.07]
2.2 short‐term treatment	14	71457	Risk Ratio (M‐H, Fixed, 95% CI)	0.96 [0.91, 1.02]
3 All‐cause mortality at ≥30 day Show forest plot	6	18481	Risk Ratio (M‐H, Fixed, 95% CI)	0.91 [0.84, 0.99]

3.1 immediate treatment	1	108	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
3.2 short‐term treatment	5	18373	Risk Ratio (M‐H, Fixed, 95% CI)	0.91 [0.84, 0.99]
4 Weighted mean change in Systolic Blood pressure during first 24 hours Show forest plot	6	738	Mean Difference (IV, Fixed, 95% CI)	‐12.54 [‐15.63, ‐9.45]

5 Weighted mean change in Diastolic Blood pressure during first 24 hours Show forest plot	6	738	Mean Difference (IV, Fixed, 95% CI)	‐3.35 [‐5.43, ‐1.28]

6 Weighted mean change in heart rate during first 24 hours Show forest plot	5	594	Mean Difference (IV, Fixed, 95% CI)	‐9.68 [‐11.99, ‐7.37]

7 Sensitivity analysis: mortality at 2 days, according to trial design Show forest plot	6	68007	Risk Ratio (M‐H, Fixed, 95% CI)	0.95 [0.85, 1.07]

7.1 Double blind trials	4	51814	Risk Ratio (M‐H, Fixed, 95% CI)	1.04 [0.91, 1.19]
7.2 Not double‐blind trials	2	16193	Risk Ratio (M‐H, Fixed, 95% CI)	0.73 [0.58, 0.91]

Comparison 3. BB

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Comparison 4. CCB

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 All‐cause mortality at 2 days Show forest plot	3	242	Risk Ratio (M‐H, Fixed, 95% CI)	2.33 [0.62, 8.78]

2 All‐cause mortality at 10 days Show forest plot	16	1988	Risk Ratio (M‐H, Fixed, 95% CI)	1.02 [0.74, 1.40]

2.1 immediate treatment	1	88	Risk Ratio (M‐H, Fixed, 95% CI)	3.0 [0.13, 71.70]
2.2 short‐term treatment	15	1900	Risk Ratio (M‐H, Fixed, 95% CI)	1.01 [0.73, 1.38]
3 All‐cause mortality at ≥30 days Show forest plot	2	198	Risk Ratio (M‐H, Fixed, 95% CI)	1.47 [0.58, 3.68]

3.1 immediate treatment	1	108	Risk Ratio (M‐H, Fixed, 95% CI)	1.4 [0.47, 4.14]
3.2 short‐term treatment	1	90	Risk Ratio (M‐H, Fixed, 95% CI)	1.64 [0.29, 9.35]
4 Weighted mean change in Systolic Blood pressure during first 24 hours Show forest plot	7	755	Mean Difference (IV, Fixed, 95% CI)	‐5.49 [‐8.42, ‐2.56]

5 Weighted mean change in Diastolic Blood pressure during first 24 hours Show forest plot	6	665	Mean Difference (IV, Fixed, 95% CI)	‐5.08 [‐7.00, ‐3.15]

6 Weighted mean change in heart rate during first 24 hours Show forest plot	5	420	Mean Difference (IV, Fixed, 95% CI)	‐1.10 [‐4.60, 2.40]

7 Sensititity analysis: mortality at 10 days, according underlying CVE Show forest plot	15	1946	Risk Ratio (M‐H, Random, 95% CI)	1.01 [0.73, 1.41]

7.1 acute myocardial infarction	10	935	Risk Ratio (M‐H, Random, 95% CI)	1.60 [0.90, 2.86]
7.2 acute stroke	5	1011	Risk Ratio (M‐H, Random, 95% CI)	0.81 [0.54, 1.21]
8 Sensitivity Analysis: mortality at 10 days, according sub‐class of CCB in AMI Show forest plot	10	935	Risk Ratio (M‐H, Random, 95% CI)	1.60 [0.90, 2.86]

8.1 Dihydropyridines	4	577	Risk Ratio (M‐H, Random, 95% CI)	1.91 [0.98, 3.72]
8.2 Non‐dihydropyridines	6	358	Risk Ratio (M‐H, Random, 95% CI)	0.92 [0.28, 3.00]

Comparison 4. CCB

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