Extrapolation of trial results suggests that aspirin is useful in intermittent claudication

Editor—In their evidence based guidelines Eccles et al conclude that aspirin is unlikely to have a beneficial effect on the incidence of major cardiovascular events in patients with intermittent claudication.¹ In contrast, an editorial by Fowkes et al suggests that aspirin may be effective, and thus warranted, even in asymptomatic peripheral vascular disease.²

Surprisingly, these opposite statements are both claimed to draw largely on the work of the Antiplatelet Trialists’ Collaboration.³ Only four studies, however, have specifically compared aspirin with placebo in peripheral vascular disease, in a total of 494 patients given aspirin and 484 controls given placebo; 56 events occurred in the aspirin group and 56 in the placebo group, and the relative risk reductions with aspirin ranged from 24% to −90% in the different trials.³ The number of randomised trials is therefore too small to lead to a conclusion about the efficacy of aspirin in peripheral vascular disease.

On the other hand, the thrombosis prevention trial has shown that aspirin is efficacious in the primary prevention of cardiac ischaemic events in patients with a relatively low risk profile (1% yearly incidence of events in the control group v an average 9% in the controls in the intermittent claudication trials).⁴ The benefits of antiplatelet treatment are larger when the risk of vascular events is higher, while bleeding is likely to be the same.²,⁴ Intermittent claudication is associated with a twofold to fivefold increased relative risk of ischaemic cardiovascular disease.² Thus the suggestion that aspirin is not effective in reducing the first occurrence of ischaemic cardiovascular disease in peripheral vascular disease seems unlikely. This controversy is reminiscent of that about the effectiveness of aspirin in the secondary prevention of myocardial infarction, when only a meta-analysis of six randomised trials, in over 10 000 patients, showed the efficacy of aspirin.⁵

Insufficient data are available on antiplatelet treatment, particularly with aspirin, in peripheral vascular disease, and new trials will probably show a considerable benefit from treatment. A precise definition of aspirin’s effects in peripheral vascular disease will help to clarify the reported advantage with clopidogrel, an antiplatelet drug recently registered in Europe.

We agree with Eccles et al that there is no direct evidence for the efficacy of aspirin in intermittent claudication, but as clinicians we feel uncomfortable not to prescribe aspirin in patients with a high cardiovascular risk profile.² Treatment recommendations in grey areas in which insufficient randomised evidence is available may reasonably come from the extrapolation of results obtained in similar categories of patients.