Fibrinolytic agents for peripheral arterial occlusion

Cochrane Database Syst Rev. 2010 Mar 17;(3):CD001099. doi: 10.1002/14651858.CD001099.pub2.

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.

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.

Publication types

  • Meta-Analysis
  • 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