Disparities by sex in P2Y12 inhibitor therapy duration, or differences in the balance of ischaemic-benefit and bleeding-risk clinical outcomes in older women versus comparable men following acute myocardial infarction? A P2Y12 inhibitor new user retrospective cohort analysis of US Medicare claims data

Abstract

Objectives: To determine if comparable older women and men received different durations of P2Y₁₂ inhibitor therapy following acute myocardial infarction (AMI) and if therapy duration differences were justified by differences in ischaemic benefits and/or bleeding risks.

Design: Retrospective cohort.

Setting: 20% sample of 2007-2015 US Medicare fee-for-service administrative claims data.

Participants: ≥66-year-old P2Y₁₂ inhibitor new users following 2008-2013 AMI hospitalisation (N=30 613). Older women compared to older men with similar predicted risks of study outcomes.

Primary and secondary outcome measures: Primary outcome: P2Y₁₂ inhibitor duration (modelled as risk of therapy discontinuation).

Secondary outcomes: clinical events while on P2Y₁₂ inhibitor therapy, including (1) death/hospice admission, (2) composite of ischaemic events (AMI/stroke/revascularisation) and (3) hospitalised bleeds. Cause-specific risks and relative risks (RRs) estimated using Aalen-Johansen cumulative incidence curves and bootstrapped 95% CIs.

Results: 10 486 women matched to 10 486 men with comparable predicted risks of all 4 study outcomes. No difference in treatment discontinuation was observed at 12 months (women 31.2% risk; men 30.9% risk; RR 1.01; 95% CI 0.97 to 1.05), but women were more likely than men to discontinue therapy at 24 months (54.4% and 52.9% risk, respectively; RR 1.03; 95% CI 1.00 to 1.05). Among patients who did not discontinue P2Y₁₂ inhibitor therapy, women had lower 24-month risks of ischaemic outcomes than men (13.1% and 14.7%, respectively; RR 0.90; 95% CI 0.84 to 0.96), potentially lower 24-month risks of death/hospice admission (5.0% and 5.5%, respectively; RR 0.91; 95% CI 0.82 to 1.02), but women and men both had 2.5% 24-month bleeding risks (RR 0.98; 95% CI 0.82 to 1.14).

Conclusions: Risks for death/hospice and ischaemic events were lower among women still taking a P2Y₁₂ inhibitor than comparable men, with no difference in bleeding risks. Shorter P2Y₁₂ inhibitor durations in older women than comparable men observed between 12 and 24 months post-AMI may reflect a disparity that is not justified by differences in clinical need.

Keywords: clinical pharmacology; epidemiology; geriatric medicine; myocardial infarction; statistics & research methods.