Fibrinolytic agents for peripheral arterial occlusion.
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.


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


METHODS
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.


METHODS
RCTs comparing fibrinolytic agents to treat peripheral arterial occlusion.


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


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).


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.
Robertson
Iain
I
Department of Radiology, Gartnavel General Hospital, 1053 Great Western Road, Glasgow, UK, G12 0XN.
Kessel
David O
DO
Berridge
David C
DC
D001157:Arterial Occlusive Diseases / Q000188:drug therapy*; D005343:Fibrinolytic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D016491:Peripheral Vascular Diseases / Q000188:drug therapy*; D016032:Randomized Controlled Trials as Topic; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use; D013300:Streptokinase / Q000009:adverse effects / Q000627:therapeutic use; D015912:Thrombolytic Therapy / Q000009:adverse effects / Q000379:methods*; D013927:Thrombosis / Q000188:drug therapy*; D010959:Tissue Plasminogen Activator / Q000009:adverse effects / Q000627:therapeutic use; D014568:Urokinase-Type Plasminogen Activator / Q000009:adverse effects / Q000627:therapeutic use
D005343:Fibrinolytic Agents; D011994:Recombinant Proteins; D013300:Streptokinase; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator