'No convincing alternative' to aspirin for secondary cardiovascular prevention, meta-analysis suggests

In a meta-analysis of randomised trials, patients who received a P2Y12 inhibitor for secondary prevention of cardiovascular events had a borderline reduction in the risk of myocardial infarction compared with those who received aspirin.

P2Y12 inhibitors provide more profound platelet inhibition than aspirin but appear to offer similar clinical benefits in secondary cardiovascular prevention. | GETTY IMAGES
P2Y12 inhibitors provide more profound platelet inhibition than aspirin but appear to offer similar clinical benefits in secondary cardiovascular prevention. | GETTY IMAGES

Italian researchers identified a total of 9 randomised controlled trials (n=42,108) comparing P2Y12 inhibitors (clopidogrel, ticagrelor or ticlopidine) and aspirin as monotherapy in patients with cerebrovascular, coronary, or peripheral artery disease.

Their meta-analysis showed that patients who received a P2Y12 inhibitor had a lower risk of myocardial infarction than those who received aspirin (odds ratio [OR] 0.81, 95% CI 0.66–0.99), equating to 244 patients needing to be treated with P2Y12 inhibitors to prevent one myocardial infarction.

Compared with the patients who received aspirin, there was no difference in the P2Y12-inhibitor-treated patients in the risk of stroke (OR 0.93, 95% CI 0.82–1.06), all-cause mortality (OR 0.98, 95% CI 0.89–1.08) or vascular death (OR 0.97, 95% CI 0.86–1.09). The risk of major bleeding was also comparable (OR 0.90, 95% CI 0.74–1.10).

Findings were consistent for the three P2Y12 inhibitors.

The researchers concluded that the benefit of P2Y12 inhibitor monotherapy is 'of debatable clinical relevance', given the high number needed to treat to prevent a myocardial infarction and the lack of effect on all-cause and vascular mortality.

Drug of choice

The authors of a linked commentary agree that aspirin monotherapy remains the standard of care for secondary prevention of cardiovascular disease. 

They say the main strength of the meta-analysis is that it includes evidence for ticagrelor, rather than just clopidogrel and ticlopidine, although they point out several limitations including the large influence of one particular trial on the results and the fact that only 3 of the trials were published in the last 5 years. 

Efforts to replace aspirin with other antiplatelet agents 'have not produced results convincing enough to induce a major change in guideline recommendations', they point out.

'Our impression is that the absence of substantial difference between the two approaches supports the use of aspirin—the drug is easier to take, associated with less non-compliance, fewer off-target side-effects (compared with ticagrelor in particular), and less variation in treatment response (compared with clopidogrel), and is likely to be more cost-effective.'

European guidelines recommend aspirin as the drug of choice for secondary prevention in patients with chronic coronary syndromes, with clopidogrel recommended as an alternative for patients with aspirin intolerance or increased risk of gastrointestinal bleeding.

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