ADAPTABLE: No sex-based difference seen in aspirin effectiveness for secondary ASCVD prevention

Sex does not appear to influence the effectiveness of aspirin at either high or low doses for the secondary prevention of atherosclerotic cardiovascular disease (ASCVD), according to the secondary analysis of the ADAPTABLE* trial.

Over a median follow-up of 26.2 months, the primary effectiveness endpoint of all-cause death and hospitalization for myocardial infarction (MI) or stroke occurred in 8.1 percent of female patients and 7.1 percent of male patients, with no significant differences between the 81- and 325-mg aspirin dosing arms (females: adjusted hazard ratio [aHR], 1.01, 95 percent confidence interval [CI], 0.82–1.26; males: aHR, 1.06, 95 percent CI, 0.91–1.23; p=0.74). [JAMA Cardiol 2024;doi:10.1001/jamacardio.2024.1712]

However, when both aspirin dosing arms were pooled, female patients had a significantly higher rate of hospitalization for stroke (aHR, 1.72, 95 percent CI, 1.27–2.33; p<0.001) but a lower rate of coronary revascularization procedures (5.0 percent vs 6.6 percent; aHR, 0.79, 95 percent CI, 0.68–0.92; p=0.002) compared with male patients, the investigators reported.

As for the safety endpoint, the overall major bleeding rates were very low at 0.64 percent, with no significant difference seen between the two aspirin dosing arms overall and when stratified by sex. Among female patients, bleeding rate was slightly higher with the 81-mg vs the 325-mg aspirin dose (0.83 percent vs 0.52 percent; aHR, 2.21, 95 percent CI, 1.04–4.70; p=0.07), a finding which the investigators advised interpreting with caution given the small number of bleeding events and the lack of statistical significance on interaction testing.

Finally, aspirin dose adherence did not vary by sex. The proportion of male female patients in the 81-mg aspirin dosing arm who discontinued treatment or switched to the high dose was 10.3 percent and 13.4 percent, respectively.

Overall, the data indicate that aspirin use for secondary prevention in ASCVD patients showed no variation in safety or effectiveness based on sex, the investigators said.

“None of the primary or secondary prevention guidelines provide sex-specific recommendations on aspirin use or dosage but encourage shared decision-making between patient and clinician. As such, our study and others will help to inform clinical decisions and discussions,” they added. [JAMA 2022;328:672-673; JAMA 2016;316:709-710]

The secondary analysis of ADAPTABLE included 15,076 patients with chronic, stable ASCVD (median age 67.6 years), of which 4,724 were female (31.3 percent) and 10,352 were male (68.7 percent). Overall, 50.6 percent of male patients and 48.8 percent of female patients received aspirin 81 mg daily, while 49.4 percent and 51.2 percent, respectively, received 325 mg.

Compared with males, females were younger (median age, 66.3 vs 68.2 years), had a slightly higher BMI (median, 31.0 vs 29.7 kg/m²), were less likely to be White (72.5 percent vs 82.7 percent), more likely to smoke (12.9 percent vs 8.4 percent), more likely to have a history of peripheral arterial disease (25.7 percent vs 23.0 percent).

Moreover, female patients presented with a higher burden of comorbidities, including diabetes (42.7 percent vs 36.9 percent), congestive heart failure (27.0 percent vs 22.5 percent), prior cerebrovascular disease (21.0 percent vs 16.5 percent), prior chronic obstructive pulmonary disease (24.5 percent vs 16.4 percent), and chronic kidney disease (19.0 percent vs 17.6 percent).

The study was limited by the limited representation of female patients, as with most trials in coronary artery disease, as well as the occurrence of study drug discontinuation and dose switching, which the investigators noted was an important problem.

Also, “this was a subgroup analysis from the main study where the results did not show a significant difference between the two aspirin groups. Therefore, any finding would clearly be hypothesis generating and will require further study to truly validate these findings,” they said.

*Aspirin Dosing: A Patient-Centric Trial Assessing Benefits and Long-Term Effectiveness