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

Robertson I, Kessel DO, Berridge DC

Published Online:

March 17, 2010

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.

Abstract (click to read)

Background:

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.

Objectives:

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

Search strategy:

The Cochrane Peripheral Vascular Diseases Group searched their Specialised Register (last searched October 2009) and the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library (last searched 2009, Issue 4) 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 patients with a range of clinical indications were included. 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 patients 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.

This record should be cited as:

Robertson I, Kessel DO, Berridge DC. Fibrinolytic agents for peripheral arterial occlusion. Cochrane Database of Systematic Reviews 2010, Issue 3. Art. No.: CD001099. DOI: 10.1002/14651858.CD001099.pub2

Assessed as up to date:

December 21, 2009

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Primary Review Group:

Peripheral Vascular Diseases Group

PEARLS - Practical Evidence About Real Life Situations (click to read)

Clinical question:

Which are the most effective fibrinolytic agents for peripheral arterial occlusion?

Bottom line:

There was some evidence to suggest intra-arterial (IA) recombinant tissue plasminogen activator (rt-PA) was more effective than IA streptokinase or intravenous (IV) rt-PA in improving vessel patency in people with peripheral arterial occlusion (PAO). There was no evidence IA rt-PA was more effective than IA urokinase for patients with PAO. There was some evidence initial lysis may be more rapid with rt-PA, depending on the regimen. The incidence of haemorrhagic complications varied with fibrinolytic regimen but there were no statistically significant differences between IA urokinase and IA rt-PA. IV rt-PA and IA streptokinase were associated with a significantly higher risk of haemorrhagic complications than IA rt-PA. The drugs investigated were streptokinase, urokinase, rt-PA and pro-urokinase.

Caveat:

No particular drug was more effective in preventing limb loss or death than another. All of the findings came from small studies, and the general paucity of results means it is not possible to draw clear conclusions.

Context:

Peripheral arterial thrombolysis is used in the management of peripheral arterial ischaemia. Streptokinase was originally used but safety concerns have led to the introduction of other agents such as urokinase and rt-PA. These newer agents were thought to have potential advantages, such as improved safety, greater efficacy, and a more rapid response.

Cochrane Systematic Review:

Robertson I et al. Fibrinolytic agents for peripheral arterial occlusion. Cochrane Reviews 2010, Issue 3. Article No. CD001099. DOI: 10.1002/14651858.CD001099.pub2. This review contains 5 studies involving 687 participants.

Authored by:

Brian R McAvoy

Cochrane Primary Health Care Field

Health topics:

Heart & circulation > Peripheral vascular disease > Peripheral arterial occlusive disease

Cochrane Summaries^beta

Independent high-quality evidence for health care decision making

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

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