Intervention Review

Fibrinolytic agents for peripheral arterial occlusion

  1. Iain Robertson1,*,
  2. David O Kessel2,
  3. David C Berridge3

Editorial Group: Cochrane Peripheral Vascular Diseases Group

Published Online: 19 DEC 2013

Assessed as up-to-date: 21 MAR 2013

DOI: 10.1002/14651858.CD001099.pub3

How to Cite

Robertson I, Kessel DO, Berridge DC. Fibrinolytic agents for peripheral arterial occlusion. Cochrane Database of Systematic Reviews 2013, Issue 12. Art. No.: CD001099. DOI: 10.1002/14651858.CD001099.pub3.

Author Information

  1. 1

    Gartnavel General Hospital, Department of Radiology, Glasgow, UK

  2. 2

    Leeds Teaching Hospitals Trust, Department of Clinical Radiology, Leeds, West Yorkshire, UK

  3. 3

    Leeds General Infirmary, Leeds Vascular Institute, Leeds, Yorkshire, UK

*Iain Robertson, Department of Radiology, Gartnavel General Hospital, 1053 Great Western Road, Glasgow, G12 0XN, UK.

Publication History

  1. Publication Status: New search for studies and content updated (no change to conclusions)
  2. Published Online: 19 DEC 2013




  1. Top of page
  2. Abstract
  3. Plain language summary


Peripheral arterial thrombolysis is used in the management of peripheral arterial ischaemia. Streptokinase was originally used but safety concerns led to a search for other agents. Urokinase and recombinant tissue plasminogen activator (rt-PA) have increasingly become established as first line agents for peripheral arterial thrombolysis. Potential advantages of these agents include improved safety, greater efficacy and a more rapid response. Recently drugs such as pro-urokinase, recombinant staphylokinase and alfimperase have been introduced. This is an update of a review first published in 2010.


To determine which fibrinolytic agents are most effective in peripheral arterial ischaemia.

Search methods

For this update the Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator (TSC) searched the Specialised Register (last searched March 2013) and CENTRAL (2013, Issue 3) for randomised controlled trials (RCTs) comparing fibrinolytic agents to treat peripheral arterial ischaemia.

Selection criteria

RCTs comparing fibrinolytic agents to treat peripheral arterial occlusion.

Data collection and analysis

Data were analysed for the outcomes vessel patency, time to lysis, limb salvage, amputation, death, complications including major haemorrhage, stroke, and distal embolization.

Main results

Five RCTs involving a total of 687 participants with a range of clinical indications were included. No new studies were included in this update. In one three-pronged study, vessel patency was greater with intra-arterial recombinant tissue plasminogen activator (rt-PA) than with intra-arterial streptokinase (P < 0.04) or intravenous rt-PA (P < 0.01). In participants with peripheral arterial occlusion there was no statistically significant difference in limb salvage at 30 days with either urokinase or rt-PA, though this may reflect the small numbers in the studies. Incidences of haemorrhagic complications varied with fibrinolytic regime but there was no statistically significant difference between intra-arterial urokinase and intra-arterial rt-PA. In the three-pronged study intravenous rt-PA and intra-arterial streptokinase were associated with a significantly higher risk of haemorrhagic complications than with intra-arterial rt-PA (P < 0.05).

Authors' conclusions

There is some evidence to suggest that intra-arterial rt-PA is more effective than intra-arterial streptokinase or intravenous rt-PA in improving vessel patency in people with peripheral arterial occlusion. There was no evidence that rt-PA was more effective than urokinase for patients with peripheral arterial occlusion and some evidence that initial lysis may be more rapid with rt-PA, depending on the regime. Incidences of haemorrhagic complications were not statistically significantly greater with rt-PA than with other regimes. However, all of the findings come from small studies and a general paucity of results means that it is not possible to draw clear conclusions.


Plain language summary

  1. Top of page
  2. Abstract
  3. Plain language summary

Drugs to break down blood clots for people with sudden onset peripheral arterial occlusion

Acute reduction in blood flow to a limb can be caused by a blood clot blocking an artery or a vascular graft. If not treated promptly this condition, known as peripheral arterial occlusion, can result in amputation or be life threatening. Infusion of clot-busting drugs can restore blood flow by dissolving the clot (thrombolysis). This review found some evidence from five randomized controlled trials, involving a total of 687 patients that suggested local infusion of a drug into the affected artery is more effective than infusion into a vein, and is also associated with a lower risk of unwanted bleeding. No particular drug was more effective in preventing limb loss or death than another. The drugs investigated were streptokinase, urokinase, recombinant tissue plasminogen activator and pro-urokinase. More research is needed to confirm these findings. All of the findings of this review came from small studies that involved people with peripheral arterial ischaemia of differing severity.