Fibrinolytic agents for peripheral arterial occlusion

Cochrane Database Syst Rev. 2013 Dec 19;(12):CD001099. doi: 10.1002/14651858.CD001099.pub3.

Abstract

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. This is an update of a review first published in 2010.

Objectives: 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.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Arterial Occlusive Diseases / drug therapy*
  • Fibrinolytic Agents / adverse effects
  • Fibrinolytic Agents / therapeutic use*
  • Humans
  • Peripheral Vascular Diseases / drug therapy*
  • Randomized Controlled Trials as Topic
  • Recombinant Proteins / adverse effects
  • Recombinant Proteins / therapeutic use
  • Streptokinase / adverse effects
  • Streptokinase / therapeutic use
  • Thrombolytic Therapy / adverse effects
  • Thrombolytic Therapy / methods*
  • Thrombosis / drug therapy*
  • Tissue Plasminogen Activator / adverse effects
  • Tissue Plasminogen Activator / therapeutic use
  • Urokinase-Type Plasminogen Activator / adverse effects
  • Urokinase-Type Plasminogen Activator / therapeutic use

Substances

  • Fibrinolytic Agents
  • Recombinant Proteins
  • Streptokinase
  • Tissue Plasminogen Activator
  • Urokinase-Type Plasminogen Activator