No Sex Differences Identified in Aspirin Dosing for Secondary Prevention of ASCVD

No sex-specific differences were identified between male and female patients with atherosclerotic cardiovascular disease (ASCVD) between receiving 81-mg and 325-mg aspirin doses daily, a new study has found.¹

In this secondary analysis of the ADAPTABLE trial, researchers aimed to evaluate primary effectiveness and safety outcomes between male and female patients with ASCVD who received 2 doses of aspirin

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In recent years, low-dose aspirin (75-100 mg orally daily) has been considered as primary prevention for ASCVD among adults aged 40 to 70 years who are at higher ASCVD risk but not at increased bleeding risk.² Although aspirin is recommended for the secondary prevention of ASCVD, it is unknown whether sex differences exist for the efficacy and safety of the drug.

In this secondary analysis of the ADAPTABLE trial, researchers aimed to evaluate primary effectiveness and safety outcomes between male and female patients with ASCVD who received 2 doses of aspirin. The open label, pragmatic, randomized clinical trial is published in JAMA Cardiology.¹

“In the ADAPTABLE trial, the overall major bleeding rates were very low, and no difference in major bleeding was noted between the 2 aspirin doses overall and when stratified by sex,” wrote the researchers of the study. “Therefore, there was no observed effect of sex on the safety and effectiveness of aspirin when used for secondary prevention in patients with ASCVD.”

The study was conducted at 40 centers and 1 health plan participating in PCORnet, The National Patient-Centered Outcomes Research Network, supported by the Patient-Centered Outcomes Research Institute. In the study, patients were randomly assigned to self-administer 81 mg or 325 mg of daily aspirin. Eligible patients were 18 years and older with established ASCVD. Demographic characteristics collected were age, sex, race, ethnicity, current tobacco use, and medication use before randomization.

The primary effectiveness outcome was the time to first occurrence of any event in the composite of all-cause death or hospitalization for myocardial infarction (MI) or stroke. The primary safety outcome was hospitalization for major bleeding requiring transfusion.

A total of 15,076 individuals were identified, including 10,352 (68.7%) male patients and 4724 (31.35%) female patients. Patients were followed for a median (IQR) of 26.2 (19-34.9) months. Of the female patients, 2307 (48.8%) received aspiring 81 mg. Female patients were younger, less likely to self-report White race, more likely to smoke, and more likely to have a history of peripheral arterial disease compared with male patients.

All-cause death and hospitalization for MI or stroke occurred in 379 (8.1%) female patients and 780 (7.1%) male patients. No significant differences were identified by sex for the primary effectiveness end point between the 2 aspirin doses (female adjusted HR [aHR], 1.01; 95% CI, 0.82-1.26 vs male aHR, 1.06; 95% CI, 0.91-1.23; P = .74).

Additionally, female patients had fewer revascularization procedures (237 vs 680; aHR, 0.79; 95% CI, 0.68-0.92; P = .002) but had a higher risk of hospitalization for stroke (aHR, 1.72; 95% CI, 1.27-2.33; P < .001). Female patients also had a slightly higher rate of bleeding in the 81-mg aspirin cohort compared with patients in the 325-mg cohort (20 vs 13; aHR, 2.21; 95% CI, 1.04-7.40; P = .07). Furthermore, no significant sex differences were found regarding aspirin dose adherence.

The researchers acknowledged some limitations to their findings, including patients not being stratified by sex before randomization, only 30% of patients enrolled were female, and this was a subgroup analysis from the main study where the results did not show a significant difference between the 2 aspirin groups.

Despite these limitations, the researchers believe the study found no significant sex-specific differences in the primary effectiveness and safety outcomes of 2 doses of aspirin for the secondary prevention of ASCVD.

“Among the female participants in this study, the lower dose of aspirin was associated with a lower, but not significantly different, mortality rate, even though more bleeding was observed with the lower dose among female participants,” wrote the researchers. “This latter finding should be interpreted with caution given the small number of bleeding events and the lack of statistical significance on interaction testing. Nevertheless, these findings may warrant further study given the size of this subgroup and the dose switching observed in the ADAPTABLE study.”

References

1. Benziger CP, Stebbins A, Wruck LM, et al. Aspirin dosing for secondary prevention of atherosclerotic cardiovascular disease in male and female patients. JAMA Cardiol. Published online July 10, 2024. doi:10.1001/jamacardio.2024.1712

2. Steven MW, Dominick JA. Aspirin for primary prevention of cardiovascular disease: what we now know. J Cardiol Cardiovasc Med. 2024;9(1):6-13. doi:10.29328/journal.jccm.1001172