STUDY OBJECTIVE

Identify optimal P2Y inhibitor durations balancing ischemic-benefit and bleeding-risk outcomes after acute myocardial infarction (AMI) in older men and women.

DESIGN

Observational retrospective cohort with 2 years of follow-up, using clone-censor-weight marginal structural models to emulate randomization.

SETTING

20 % sample of US Medicare administrative claims data.

PARTICIPANTS

P2Y inhibitor new users ≥66 years old following 2008-2013 AMI hospitalization.

EXPOSURES

12- to 24-month P2Y inhibitor durations in 1-month intervals.

MAIN OUTCOME MEASURES

Effectiveness outcome (composite of all-cause mortality, recurrent AMI, ischemic stroke), safety outcome (hospitalized bleed), and negative control outcome (heart failure hospitalization).

RESULTS

Of 28,488 P2Y inhibitor new users, 51 % were female, 50 % were > 75 years old, 88 % were White/non-Hispanic, and 93 % initiated clopidogrel. Negative control outcome results for 16- through 24-month durations appeared most likely to meet assumptions of no unmeasured confounding. Compared to men taking 24-month therapy, men taking 16-month therapy had higher 2-year risks of the composite effectiveness outcome (relative risk [RR] = 1.08; 95 % confidence interval [95%CI]:1.00-1.15) with similar bleeding risks (RR = 0.98; 95%CI:0.85-1.13). Compared to women taking 24-month therapy, women taking 16-month therapy had similar 2-year risks of the composite effectiveness outcome (RR = 0.98; 95%CI:0.92-1.04) and lower bleeding risks (RR = 0.88; 95%CI:0.80-0.96).

CONCLUSIONS

Older men taking 24-month P2Y inhibitor therapy had the lowest composite effectiveness outcome risk with no increased bleeding risk compared to shorter durations. Women taking 16-month versus 24-month P2Y inhibitor therapy had similar composite effectiveness outcome risks but a substantially lower hospitalized bleeding risk, suggesting durations beyond 15-17 months lacked benefit while increasing bleeding risk.