What is the risk of cardiovascular morbidity?

The increased risk of vascular disease in a subgroup of patients judged to be “resistant” to aspirin led Krasopoulos et al to propose that there could be beneficial effect of aspirin of greater than 50% in aspirin sensitive patients.¹

The problem is identifying subjects “resistant” to aspirin. Krasopoulos et al accepted evidence from the authors of 20 reports of randomised aspirin trials of an inhibition of the expected platelet response to aspirin, however measured. The platelet tests had been done in hospital before the patients were admitted to the trials. The authors therefore dismiss the possibility that the lack of benefit during the trial was simply due to poor compliance with aspirin taking.

Compliance could still partly explain the findings. In one study only one of the 17 patients who had been judged to be aspirin resistant failed to show the expected platelet response to aspirin when aspirin was taken under close supervision.²

Paradoxically, although platelet aggregation showed a large range in men in a large cohort, there was no evidence that the degree of platelet aggregation is predictive of subsequent heart disease events.^{3 4}

The authors’ estimate of the beneficial effect of aspirin in sensitive patients is remarkably close to the 51% reduction reported for the doctors in the US physicians health study who claimed that they had taken aspirin regularly, compared with a 17% reduction in those who admitted that they had taken the drug on less than half the days.⁵

The application of the term increased risk to the patients with aspirin resistance (at the foot of fig 3) is unfortunate. Whether aspirin “resistance” carries an increased vascular risk cannot be judged in trials without placebo groups.