Efficacy and safety of P2Y12 inhibitors comparable between men and women

Background

The efficacy and safety of P2Y12 inhibitors in women is not adequately established, due to their underrepresentation in clinical studies [1,2]. There are concerns because of gender-specific differences in the pharmacodynamics and due to the fact that women are at increased risk of bleeding after acute coronary syndrome (ACS) and percutaneous coronary intervention (PCI) [3-6].

In this meta-analysis of 7 phase III or IV RCTs, the gender-specific efficacy and safety of P2Y12 inhibitors prasugrel, ticagrelor and cangrelor were evaluated in patients with stable and unstable coronary artery disease (CAD). For this, end points with P2Y12 inhibitors were compared with these of clopidogrel (6 studies) or placebo (1 study).

Main results

• Of 87,840 patients, 27.9% were women. Women were significantly more likely to be older and to have comorbidities including diabetes mellitus, hypertension, prior stroke or TIA, prior heart failure and lower eGFR.
• Risk of primary endpoint MACE in women corresponded to an HR of 0.86, 95% CI 0.78-0.94, P=0.002 and in men to an HR of 0.85; 95% CI 0.80-0.90, P<0.001, without heterogeneity (P interaction = 0.93).
• Similar results were observed for the composite of cardiovascular (CV) death, myocardial infarction (MI) or stroke (HR in women 0.89, 95% CI 0.81-0.97, P=0.01, HR in men 0.85, 95% CI 0.80-0.90, P<0.001, P interaction = 0.60).
• In women, risk of MI (HR 0.87, 95% CI 0.78-0.96, P=0.01), CV death (HR 0.87, 95% CI 0.76-1.01, P=0.06) and risk of stroke were reduced (HR 0.92, 95% CI 0.55-1.56, P=0.76).
• In men, risk of CV death (HR 0.85, 95% CI 0.77-0.95, P=0.002, P interaction = 0.86) and of MI were reduced (HR 0.84, 95% CI 0.76-0.91, P<0.001, P interaction = 0.65), and effect was neutral effect on risk of stroke (HR 0.99, 95% CI 0.82-1.18, P=0.87, P interaction = 0.72).
• Risk of stent thrombosis in women (HR 0.49, 95% CI 0.37-0.65, P<0.001) and in men (HR 0.59, 95% CI 0.42-0.84, P=0.003, P interaction = 0.85) was reduced.
• In both men and women, risk of TIMI (non–CABG-related) major bleeding increased (HR in women 1.28, 95% CI 0.87-1.88, P=0.21, HR in men 1.52, 95% CI 1.12-2.07, P<0.01, P interaction = 0.62).
• Risk of intracranial hemorrhage in men was increased (HR 1.47, 95% CI 1.02-2.11, P=0.04), but not in women (HR 0.96, 95% CI 0.46-1.98, P=0.91). However number of events were few and test for heterogeneity by gender was not significant (P interaction = 0.24).
• All-cause mortality was reduced in women (HR 0.89, 95% CI 0.78-1.01, P=0.07) and in men (HR 0.89, 95% CI 0.81-0.99, P=0.02, P interaction = 0.99).

Conclusion

References

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