Fibrinolytic agents for peripheral arterial occlusion

Iain Robertson; David O Kessel; David C Berridge

doi:10.1002/14651858.CD001099.pub3

Agents fibrinolytiques contre l'occlusion artérielle périphérique

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Referencias

References to studies included in this review

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Berridge DC, Gregson RHS, Hopkinson BR, Makin GS. Randomized trial of intra‐arterial recombinant tissue plasminogen activator, intravenous recombinant tissue plasminogen activator and intra‐arterial streptokinase in peripheral arterial thrombolysis. British Journal of Surgery 1991;78:988‐95.

Mahler F, Schneider E, Hess H, Steering Committee, Study on Local Thrombolysis. Recombinant tissue plasminogen activator versus urokinase for local thrombolysis of femoropopliteal occlusions: A prospective, randomized multicenter trial. Journal of Endovascular Therapy 2001;8(6):638‐47.

Meyerovitz MF, Goldhaber SZ, Reagan K, Polak JF, Kandarpa K, Grassi C, et al. Recombinant tissue‐type plasminogen versus urokinase in peripheral arterial and graft occlusions: A randomized trial. Radiology 1990;175:75‐8.

Ouriel K, Kandarpa K, Krishna MD, Scheurr D, Hultquist M, Hodkinson G, et al. Prourokinase vs urokinase for recanalization of peripheral occlusions, safety and efficacy: The PURPOSE trial. Journal of Vascular and Interventional Radiology 1999;10(8):1083‐91.

Schweizer J, Altmann E, Stoblein F, Florek HJ, Kaulen R. Comparision of tissue plasminogen activator and urokinase in the local infiltration thrombolysis of peripheral arterial occlusions. European Journal of Radiology 1996;22:129‐32.

References to studies excluded from this review

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Braithwaite BD, Buckenham TM, Galland RB, Heather BP, Earnshaw JJ. Prospective randomized trial of high‐dose bolus versus low‐dose tissue plasminogen activator infusion in the management of acute limb ischaemia. British Journal of Surgery 1997;84(5):646‐50.

Braithwaite BD, Virgo H, Earnshaw JJ. The systematic effects of high dose bolus and low dose intra‐arterial thrombolysis with tissue plasminogen activator (t‐PA) for acute limb ischaemia. Thrombosis and Haemostasis. 1997; Vol. 503 Abstract No PS‐2058, issue Supplement June.

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Cina CS, Goh RH, Chan J, Kenny B, Evans G, Rawlinson J, et al. Intraarterial catheter‐directed thrombolysis: urokinase versus tissue plasminogen activator. Annals of Vascular Surgery 1999;13(6):571‐5.

Dawson KJ, Reddy K, Platts AD, Hamilton G. Results of a recently instituted programme of thrombolytic therapy in acute lower limb ischaemia. British Journal of Surgery 1991;78(4):409‐11.

Dawson KJ, Hehir D, Hamilton G. Low dose intra‐arterial streptokinase compared with tissue plasminogen activator in acute lower limb ischaemia. Irish Journal of Medical Science 1991;160:216‐7.

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Didier D, Meyerovitz MF, Vogel JJ, Soulier L, Bounameaux H. Thrombolysis versus mechanical recanalisation of chronic peripheral arterial occlusions. Randomized study. Schweizerische Medizinische Wochenschrift 1995;125:11.

Dube M, Soulez G, Therasse E, Cartier P, Blair JF, Roy P, et al. Comparison of streptokinase and urokinase in local thrombolysis of peripheral arterial occlusions for lower limb salvage. Journal of Vascular and Interventional Radiology 1996;7(4):587‐93.

Duda S, Tepe G, Luz O, Ouriel K, Dietz K, Hahn U, et al. Peripheral arterial occlusion: treatment with abxcimab plus urokinase versus urokinase alone ‐ a randomised pilot trial (the PROMPT trial). Radiology 2001;221:689‐96.

Gryglewski RJ, Szczeklik A, Korbut R, Swies J, Musial J, Krzanowski M, et al. The mechanism of anti‐thrombotic, thrombolytic and fibrinolytic actions of camonagrel‐‐a new thromboxane synthase inhibitor. Wiener Klinische Wochenschrift 1995;107:283‐9.

Han SM, Weaver FA, Comerota AJ, Perler BA, Joing M. Efficacy and safety of alfimeprase in patients with acute peripheral arterial occlusion (PAO). Journal of Vascular Surgery 2010;51(3):600‐9.

Hess H, Mietaschk A, von Bilderling P, Neller P. Peripheral arterial occlusions: local low‐dose thrombolytic therapy with recombinant tissue‐type plasminogen activator (rt‐PA). European Journal of Vascular and Endovascular Surgery 1996;12(1):97‐104.

Hiatt WR. Abciximab added to urokinase increased amputation‐free survival in peripheral arterial occlusion of the legs. American College of Physicians Journal Club 2002;137(1):12.

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Reichle FA, Rao NS, Chang KHY, et al. Fibrinolytic treatment of acute or subacute arterial thrombosis. Surgical Forum 1976;27:219‐21.

Sarif J, Lindhoff‐Last E, Bauersachs R. Rebound after discontinuation of long‐term oral anticoagulation (OAC): Effects of a 4 week course of LMWH on VTE recurrences. Journal of Thrombosis and Haemostasis. 2005; Vol. 3, issue 1:Abstract no: P1024.

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Schulman S, Wiman B. The significance of hypofibrinolysis for the risk of recurrence of venous thromboembolism. Thrombosis and Haemostasis 1996;75:607‐11.

The STILE investigators. Results of a prospective randomized trial evaluating surgery versus thrombolysis for ischaemia of the lower extremity. Annals of Surgery 1994;220(3):251‐68.

Tepe G, Hopfenzitz C, Dietz K, Wiskirchen J, Heller S, Ouriel K, et al. Peripheral Arteries: Treatment with antibodies of platelet receptors and reteplase for thrombolysis‐APART trial. Radiology 2006;239(3):892‐900.

Vanderschueren S, Stockx L, Wilms G, Lacroix H, Verhaege R, Vermuylen J, et al. Thrombolytic therapy of peripheral arterial occlusion with recombinant staphylokinase. Circulation 1995;92(8):2050‐7.

Wen Y, Rong C, Yu W, Qian Z, Shu‐rong L, Ning L, et al. Effect of urokinase injected by volumetric infusion pump on rest pain, intermittent limp and walking distance in aged patients with arteriosclerosis obliterans of the lower limbs. Zhongguo Linchuang Kangfu 2005;9(30):232‐3.

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Additional references

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otras versiones publicadas

Ad Hoc Committee on Reporting Standards, Society for Vascular Surgery/North American Chapter International Society for Cardiovascular Surgery. Suggested standards for reports dealing with lower extremity ischaemia. Journal of Vascular Surgery 1986;4(1):80‐94.

Anonymous. Second European Consensus Document on chronic critical leg ischaemia. Circulation 1991;84 Suppl IV(4):1‐26.

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Berridge DC, Kessel D, Robertson I. Surgery versus thrombolysis for initial management of acute limb ischaemia. Cochrane Database of Systematic Reviews 2013, Issue 6. [DOI: 10.1002/14651858.CD002784.pub2]

Fontaine VR, Kim M, Kieny R. Die chirurgische Behandlung der peripheren Durchblutungsstorungen [Die chirurgische Behandlung der peripheren Durchblutungsstorungen]. Helvetica Chirurgica Acta 1954;5/6:499‐533.

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Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.0.2 [updated September 2009]. The Cochrane Collaboration, 2009. Available from www.cochrane‐handbook.org.

Kessel DO, Berridge DC, Robertson I. Infusion techniques for peripheral arterial thrombolysis. Cochrane Database of Systematic Reviews 2004, Issue 1. [DOI: 10.1002/14651858.CD000985.pub2]

References to other published versions of this review

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estudios excluidos
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Robertson I, Kessel DO, Berridge DC. Fibrinolytic agents for peripheral arterial occlusion. Cochrane Database of Systematic Reviews 2010, Issue 3. [DOI: 10.1002/14651858.CD001099.pub2]

Characteristics of studies

Characteristics of included studies [ordered by study ID]

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estudios excluidos

Berridge 1991

Methods	Study design: RCT parallel group.
Participants	Country: United Kingdom. Setting: hospital. No of patients: 60; 20 i.v. rt‐PA, 20 i.a. SK, 20 i.a. rt‐PA. Mean age: 71 years. Gender: 39 M; 21 F. Inclusion criteria: peripheral lower limb ischaemia <30 days duration. Exclusion criteria: clinically apparent arterial emboli treated with surgical embolectomy.
Interventions	Treatment: 3 infusion protocols. (i) i.a. streptokinase infused at 5000 U/hr with 250 U/hr heparin (20pts); (ii) i.a rt‐PA 0.5 mg/hr with 250 U/hr heparin; (iii) i.v. rt‐PA max total dose 100 mg rt‐PA at 4 rates of infusion 1, 2, 5 and 10 mg/hr. Duration of treatment: complete lysis achieved or patient deterioration or lytic stagnation after a 12 hr period. Follow up: 30 days and 3 months.
Outcomes	Primary: limb salvage, amputation, death. Secondary: death, major haemorrhage.
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Random number generator.
Allocation concealment (selection bias)	Unclear risk	Information on allocation concealment not provided.
Blinding (performance bias and detection bias) All outcomes	High risk	Not blinded.
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Exclusions post‐randomisation: 6 not included in the analysis. Lost to follow up: none.
Selective reporting (reporting bias)	Low risk	All outcomes reported.
Other bias	Unclear risk	Study financially supported by Boehringer Ingelheim who supplied recombinant tissue plasminogen activator.

Mahler 2001

Methods	Study design: prospective RCT.
Participants	Country: Germany and Switzerland. Setting: hospital. No of patients: 234. Mean age: 69.5 years rt‐PA; 70.1 years UK. Gender: M 81 (65%) rt‐PA; M 64 (58%) UK. Inclusion criteria: angiographically documented thrombotic or embolic occlusions five to 40 cm length. Exclusion criteria: thrombi > 6 months old or emboli > 6 weeks. Standard exclusions for increased bleeding risk from thrombolysis.
Interventions	(i) rt‐PA; (ii) UK; Either end hole catheter or microporous balloon. End hole catheter 2.5 mg/hr rt‐PA or 100,000 IU/hr UK. Microporous balloon 0.5 mg/cm thrombus length rt‐PA or 20,000 IU/cm thrombus length. Duration of treatment: end hole catheter serially advanced. Microporous balloon one hour if complete lysis not achieved then infusion lysis and secondary intervention. Follow up: end of lysis and at six months; 81% reached six month follow up.
Outcomes	Primary: vessel patency, time to lysis, amputation, death. Secondary: complications including bleeding and cerebral haemorrhage.
Notes	Techniques not randomised ‐ dependant on local practice ‐ but use of rt‐PA or UK was randomised. Complex trial as two infusion techniques used; the microporous balloon more rapid pharmacomechanical action but no difference in outcomes by technique or drug at follow up.
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Randomised in blocks of 10.
Allocation concealment (selection bias)	Unclear risk	Method not stated.
Blinding (performance bias and detection bias) All outcomes	High risk	Not blinded.
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	55 patients lost to follow up but no information on statistical handling of missing data. Exclusion post‐randomisation: none recorded.
Selective reporting (reporting bias)	Low risk	All primary and secondary outcomes reported.
Other bias	Unclear risk	Supported by a grant from Boehringer Ingelheim who manufactured the Alteplase.

Meyerovitz 1990

Methods	Study design: RCT.
Participants	Country: USA. Setting: hospital. No of patients: 32. Mean age: 58 years. Gender: 22 M and 10 F. Inclusion criteria: native/bypass occlusion < 90. Exclusion criteria: standard exclusions for increased bleeding risk from thrombolysis.
Interventions	(i) rt‐PA 10 mg intrathrombic dose then 5 mg/hr up to 24 hours. (ii) UK dose 60,000 IU intrathrombic bolus and 240,000 IU/h for two hrs, 120,000 IU/h for two hrs and 60,000 IU for up to 20 hours. Duration of treatment: 24 hours. Follow up: end of lysis for degree of lysis and surgery, angioplasty, death, limb loss within 30 days.
Outcomes	Primary: 95% lysis and restoration of flow, time to lysis. Secondary: surgery, angioplasty, death, limb loss within 30 days, blood transfusion (major haemorrhage) within 72 hours.
Notes	Lysis continued for 18 to 72 hours in 6 urokinase (4 successful). Lysis continued for 2 pts with urokinase who received rt‐PA unsuccessfully.
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Randomised by means of consecutive numbers.
Allocation concealment (selection bias)	Unclear risk	Sealed envelopes.
Blinding (performance bias and detection bias) All outcomes	High risk	Not blinded.
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Exclusions post‐randomisation: none recorded. No losses to follow up.
Selective reporting (reporting bias)	Low risk	All outcomes reported.
Other bias	Unclear risk	Supported in part by Genentech Inc (Activase manufacturer) and Abbott Laboratories (Abbokinase manufacturer).

Ouriel 1999

Methods	Phase II randomised, multicentre double blind study.
Participants	Country: USA. Setting: hospital. No of patients: 241. Mean age: 65.1 years. Gender: M 143 (62.7%); F 85 (37.3%). Inclusion criteria: patients with lower extremity native artery or graft occlusion of less than or equal to 14 days duration. Exclusion criteria: standard exclusions for increased bleeding risk from thrombolysis.
Interventions	(i) pro‐urokinase 2 mg, 4 mg, 8 mg/hr for 8 hours followed by 0.5 mg/hr in each group. (ii) urokinase group 4000 IU/min for 4 hours followed by 2000 IU/min. Thrombus lacing dose based on length of occlusion. Duration of treatment: > 95% clot lysis or 24 hours. Follow up: 30 days.
Outcomes	Primary: vessel patency, time to lysis, dose of study drug, amputation, death. Secondary: complications including bleeding.
Notes	Dose response curve for pro‐urokinase derived. Fibrin specificity of prourokinase lost at equipotent doses with urokinase.
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Randomisation was stratified by type of occlusion; native artery or bypass graft.
Allocation concealment (selection bias)	Unclear risk	Method not stated.
Blinding (performance bias and detection bias) All outcomes	Low risk	Double blind.
Incomplete outcome data (attrition bias) All outcomes	Low risk	All analyses based on participants who received their randomised treatment. Of 241 patients randomised 13 patients were entered into the trial but never received the specified therapy (reasons given). No losses to follow up recorded.
Selective reporting (reporting bias)	Low risk	All outcomes reported.
Other bias	Unclear risk	Some authors were affiliated to Abbott Laboratories manufacturers of Abbokinase.

Schweizer 1996

Methods	Study design: RCT.
Participants	Country: Germany. Setting: hospital. No of patients: 120; 60 rt‐PA, 60 UK. Mean age: 65 years. Gender: M 60%, F 40% UK; M 57%, F 43% rt‐PA. Inclusion criteria: < 3 months occlusion of femoropopliteal segment. Exclusion criteria: not recorded.
Interventions	(i) rt‐PA 5 mg intrathrombic bolus followed by infusion at 5 mg/hr plus heparin 750 IU/hr. (ii) urokinase 60,000 IU/hr plus heparin 700 IU/hr. Treatment duration: rt‐PA 1 to 4 hrs (mean 2 hrs); UK 6 to 72 hrs (mean 24 hours). Follow up: 6 months follow up.
Outcomes	Primary: amputation, Fontaine, ABPI, vessel patency. Secondary: death.
Notes	Fontaine IIb claudication 49% of study population. Short occlusion lengths 6 cm.
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	States randomised but method not given.
Allocation concealment (selection bias)	Unclear risk	Not stated.
Blinding (performance bias and detection bias) All outcomes	High risk	Not blinded.
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Exclusions post‐randomisation: none recorded. Two patients lost to follow‐up but no information on statistical handling of missing data.
Selective reporting (reporting bias)	Low risk	All outcomes reported.
Other bias	Unclear risk	No declarations of interest stated, no information given regarding sponsorship.

i.a. intra‐arterial
IU international units
i.v. intravenous
RCT randomised controlled trial
rt‐PA recombinant tissue plasminogen activator
SK streptokinase
UK urokinase

Characteristics of excluded studies [ordered by study ID]

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estudios incluidos

Study	Reason for exclusion
Braithwaite 1997	Comparison of dose regimes for high and low dose rt‐PA
Cina 1999	Comparison of rt‐Pa versus urokinase but non‐randomised selection by surgeons preference
Dawson 1991	Non‐randomised streptokinase vs rt‐PA
Dawson 1991a	Non‐randomised
Didier 1995	Comparison of angioplasty versus rt‐PA and angioplasty
Dube 1996	Only partially randomised 10 of 40 patients; insufficient for analysis
Duda 2001	Not a true comparison of agents; use of abxicimab as an adjunctive agent studied. Complex randomisation 5:2 to support complication rate as major finding may have impact on study findings
Gryglewski 1995	Not a comparison of thrombolytic agents
Han 2010	Paper reports NAPA II/III trials. Not a comparison of thrombolytic agents ‐ comparison with placebo. Safety and efficacy trial with primary end point of avoidance of open vascular surgery within 30 days of treatment
Hess 1996	Non‐comparative and non‐randomised
Hiatt 2002	Not a comparison of agents
Reichle 1976	Randomised but 11 patients in one group and 6 in the other group ‐ method of randomisation not stated, clinical enrolment criteria not accurately described
Sarif 2005	Not arterial thrombolysis
Schulman 1996	Venous thromboembolism
STILE 1994	Subset of patients comparing urokinase and rt‐PA but insufficient detail reported to permit analysis. Authors report no difference between rt‐PA and urokinase
Tepe 2006	Comparison is of the effect of the addition of abxicimab to thrombolytic agents and not a true comparison of agents. More appropriately considered under infusion techniques
Vanderschueren 1995	Staphylokinase. Pilot study. No apparent randomisation. Not blinded. No control group ‐ study compared two different infusion protocols
Wen 2005	Comparison of urokinase and danshen root

rt‐PA recombinant tissue plasminogen activator

Data and analyses

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Comparison 1. Intra‐arterial streptokinase versus intravenous rt‐PA

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Vessel Patency immediately post lysis Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected
Open in figure viewer Analysis 1.1 Comparison 1 Intra‐arterial streptokinase versus intravenous rt‐PA, Outcome 1 Vessel Patency immediately post lysis.
2 Asymptomatic Limb salvage at 30 days Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected
Open in figure viewer Analysis 1.2 Comparison 1 Intra‐arterial streptokinase versus intravenous rt‐PA, Outcome 2 Asymptomatic Limb salvage at 30 days.
3 Amputation at 30 days Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected
Open in figure viewer Analysis 1.3 Comparison 1 Intra‐arterial streptokinase versus intravenous rt‐PA, Outcome 3 Amputation at 30 days.
4 Death Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected
Open in figure viewer Analysis 1.4 Comparison 1 Intra‐arterial streptokinase versus intravenous rt‐PA, Outcome 4 Death.
5 Complications‐ major haemorrhage Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected
Open in figure viewer Analysis 1.5 Comparison 1 Intra‐arterial streptokinase versus intravenous rt‐PA, Outcome 5 Complications‐ major haemorrhage.
6 Complications‐ minor haemorrhage Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected
Open in figure viewer Analysis 1.6 Comparison 1 Intra‐arterial streptokinase versus intravenous rt‐PA, Outcome 6 Complications‐ minor haemorrhage.

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Comparison 2. Intra‐arterial streptokinase versus intra‐arterial rt‐PA

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Vessel patency immediately post lysis Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected
Open in figure viewer Analysis 2.1 Comparison 2 Intra‐arterial streptokinase versus intra‐arterial rt‐PA, Outcome 1 Vessel patency immediately post lysis.
2 Asymptomatic Limb salvage at 30 days Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected
Open in figure viewer Analysis 2.2 Comparison 2 Intra‐arterial streptokinase versus intra‐arterial rt‐PA, Outcome 2 Asymptomatic Limb salvage at 30 days.
3 Amputation at 30 days Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected
Open in figure viewer Analysis 2.3 Comparison 2 Intra‐arterial streptokinase versus intra‐arterial rt‐PA, Outcome 3 Amputation at 30 days.
4 Death Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected
Open in figure viewer Analysis 2.4 Comparison 2 Intra‐arterial streptokinase versus intra‐arterial rt‐PA, Outcome 4 Death.
5 Complications‐ major haemorrhage Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected
Open in figure viewer Analysis 2.5 Comparison 2 Intra‐arterial streptokinase versus intra‐arterial rt‐PA, Outcome 5 Complications‐ major haemorrhage.
6 Complications‐ minor haemorrhage Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected
Open in figure viewer Analysis 2.6 Comparison 2 Intra‐arterial streptokinase versus intra‐arterial rt‐PA, Outcome 6 Complications‐ minor haemorrhage.

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Comparison 3. Intra‐arterial urokinase versus intra‐arterial rt‐PA

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Vessel patency immediately post lysis Show forest plot	3		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected
Open in figure viewer Analysis 3.1 Comparison 3 Intra‐arterial urokinase versus intra‐arterial rt‐PA, Outcome 1 Vessel patency immediately post lysis.
2 Limb salvage Show forest plot	3	368	Odds Ratio (M‐H, Fixed, 95% CI)	1.68 [0.68, 4.15]
Open in figure viewer Analysis 3.2 Comparison 3 Intra‐arterial urokinase versus intra‐arterial rt‐PA, Outcome 2 Limb salvage.
3 Major amputation at 30 days‐6 months Show forest plot	3		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected
Open in figure viewer Analysis 3.3 Comparison 3 Intra‐arterial urokinase versus intra‐arterial rt‐PA, Outcome 3 Major amputation at 30 days‐6 months.
4 Death Show forest plot	3	368	Odds Ratio (M‐H, Fixed, 95% CI)	0.79 [0.24, 2.54]
Open in figure viewer Analysis 3.4 Comparison 3 Intra‐arterial urokinase versus intra‐arterial rt‐PA, Outcome 4 Death.
5 Complications ‐ major haemorrhage Show forest plot	3	298	Odds Ratio (M‐H, Fixed, 95% CI)	0.68 [0.19, 2.40]
Open in figure viewer Analysis 3.5 Comparison 3 Intra‐arterial urokinase versus intra‐arterial rt‐PA, Outcome 5 Complications ‐ major haemorrhage.
6 Complications ‐ minor haemorrhage Show forest plot	3	386	Odds Ratio (M‐H, Fixed, 95% CI)	0.50 [0.20, 1.26]
Open in figure viewer Analysis 3.6 Comparison 3 Intra‐arterial urokinase versus intra‐arterial rt‐PA, Outcome 6 Complications ‐ minor haemorrhage.

Figure 1

Study flow diagram.

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Figure 2

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

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Figure 3

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

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Analysis 1.1

Comparison 1 Intra‐arterial streptokinase versus intravenous rt‐PA, Outcome 1 Vessel Patency immediately post lysis.

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Analysis 1.2

Comparison 1 Intra‐arterial streptokinase versus intravenous rt‐PA, Outcome 2 Asymptomatic Limb salvage at 30 days.

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Analysis 1.3

Comparison 1 Intra‐arterial streptokinase versus intravenous rt‐PA, Outcome 3 Amputation at 30 days.

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Analysis 1.4

Comparison 1 Intra‐arterial streptokinase versus intravenous rt‐PA, Outcome 4 Death.

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Analysis 1.5

Comparison 1 Intra‐arterial streptokinase versus intravenous rt‐PA, Outcome 5 Complications‐ major haemorrhage.

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Analysis 1.6

Comparison 1 Intra‐arterial streptokinase versus intravenous rt‐PA, Outcome 6 Complications‐ minor haemorrhage.

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Analysis 2.1

Comparison 2 Intra‐arterial streptokinase versus intra‐arterial rt‐PA, Outcome 1 Vessel patency immediately post lysis.

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Analysis 2.2

Comparison 2 Intra‐arterial streptokinase versus intra‐arterial rt‐PA, Outcome 2 Asymptomatic Limb salvage at 30 days.

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Analysis 2.3

Comparison 2 Intra‐arterial streptokinase versus intra‐arterial rt‐PA, Outcome 3 Amputation at 30 days.

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Analysis 2.4

Comparison 2 Intra‐arterial streptokinase versus intra‐arterial rt‐PA, Outcome 4 Death.

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Analysis 2.5

Comparison 2 Intra‐arterial streptokinase versus intra‐arterial rt‐PA, Outcome 5 Complications‐ major haemorrhage.

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Analysis 2.6

Comparison 2 Intra‐arterial streptokinase versus intra‐arterial rt‐PA, Outcome 6 Complications‐ minor haemorrhage.

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Analysis 3.1

Comparison 3 Intra‐arterial urokinase versus intra‐arterial rt‐PA, Outcome 1 Vessel patency immediately post lysis.

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Analysis 3.2

Comparison 3 Intra‐arterial urokinase versus intra‐arterial rt‐PA, Outcome 2 Limb salvage.

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Analysis 3.3

Comparison 3 Intra‐arterial urokinase versus intra‐arterial rt‐PA, Outcome 3 Major amputation at 30 days‐6 months.

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Analysis 3.4

Comparison 3 Intra‐arterial urokinase versus intra‐arterial rt‐PA, Outcome 4 Death.

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Analysis 3.5

Comparison 3 Intra‐arterial urokinase versus intra‐arterial rt‐PA, Outcome 5 Complications ‐ major haemorrhage.

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Analysis 3.6

Comparison 3 Intra‐arterial urokinase versus intra‐arterial rt‐PA, Outcome 6 Complications ‐ minor haemorrhage.

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Comparison 1. Intra‐arterial streptokinase versus intravenous rt‐PA

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Vessel Patency immediately post lysis Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected

2 Asymptomatic Limb salvage at 30 days Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected

3 Amputation at 30 days Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected

4 Death Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected

5 Complications‐ major haemorrhage Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected

6 Complications‐ minor haemorrhage Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected

Comparison 1. Intra‐arterial streptokinase versus intravenous rt‐PA

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Comparison 2. Intra‐arterial streptokinase versus intra‐arterial rt‐PA

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Vessel patency immediately post lysis Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected

2 Asymptomatic Limb salvage at 30 days Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected

3 Amputation at 30 days Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected

4 Death Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected

5 Complications‐ major haemorrhage Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected

6 Complications‐ minor haemorrhage Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected

Comparison 2. Intra‐arterial streptokinase versus intra‐arterial rt‐PA

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Comparison 3. Intra‐arterial urokinase versus intra‐arterial rt‐PA

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Vessel patency immediately post lysis Show forest plot	3		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected

2 Limb salvage Show forest plot	3	368	Odds Ratio (M‐H, Fixed, 95% CI)	1.68 [0.68, 4.15]

3 Major amputation at 30 days‐6 months Show forest plot	3		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected

4 Death Show forest plot	3	368	Odds Ratio (M‐H, Fixed, 95% CI)	0.79 [0.24, 2.54]

5 Complications ‐ major haemorrhage Show forest plot	3	298	Odds Ratio (M‐H, Fixed, 95% CI)	0.68 [0.19, 2.40]

6 Complications ‐ minor haemorrhage Show forest plot	3	386	Odds Ratio (M‐H, Fixed, 95% CI)	0.50 [0.20, 1.26]

Comparison 3. Intra‐arterial urokinase versus intra‐arterial rt‐PA

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Referencias

References to studies included in this review

Berridge 1991 {published data only}

Mahler 2001 {published data only}

Meyerovitz 1990 {published data only}

Ouriel 1999 {published data only}

Schweizer 1996 {published data only}

References to studies excluded from this review

Braithwaite 1997 {published data only}

Cina 1999 {published data only}

Dawson 1991 {published data only}

Dawson 1991a {published data only}

Didier 1995 {published data only}

Dube 1996 {published data only}

Duda 2001 {published data only}

Gryglewski 1995 {published data only}

Han 2010 {published data only}

Hess 1996 {published data only}

Hiatt 2002 {published data only}

Reichle 1976 {published data only}

Sarif 2005 {published data only}

Schulman 1996 {published data only}

STILE 1994 {published data only}

Tepe 2006 {published data only}

Vanderschueren 1995 {published data only}

Wen 2005 {published data only}

Additional references

Anonymous 1986

Anonymous 1991

Berridge 2013

Fontaine 1954

Higgins 2009

Kessel 2004

References to other published versions of this review

Robertson 2010

Characteristics of studies

Characteristics of included studies [ordered by study ID]

Characteristics of excluded studies [ordered by study ID]

Data and analyses

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