Apixaban shows lowest major bleeding risk in older adults with HIV and atrial fibrillation

The risk for major bleeding in patients with HIV infection and atrial fibrillation (AF) on antiretroviral therapy (ART) is higher with the use of warfarin and rivaroxaban than with apixaban, highlighting the superior safety profile of apixaban in high-risk HIV populations. These study findings were published in JAMA Internal Medicine.

The burden of HIV-associated cardiovascular disease has tripled worldwide in the past 2 decades, prompting growing concerns about the safety of anticoagulants among individuals with HIV infection.

Researchers at Harvard Medical School in Massachusetts sourced data for this study from the United States fee-for-service databases for Medicare Parts A, B, and D. The researchers evaluated patients aged 50 years and older with HIV and AF who initiated anticoagulant therapy with warfarin, rivaroxaban, or apixaban between 2013 and 2020 for major bleeding-associated hospitalization. The researchers used propensity score overlap weighting to balance for cohort differences and compare outcomes between warfarin (n=1163) vs apixaban (n=1520) recipients, rivaroxaban (n=629) vs apixaban (n=1547) recipients, and rivaroxaban (n=625) vs warfarin (n=1162) recipients.

Among patients included in the final analysis, the mean age ranged from 65.8 to 66.5 years, 20.6% to 21.6% were women, 52.4% to 62.6% were White, and 69% to 72% reported use of ART.

In comparisons between apixaban and warfarin recipients, apixaban and rivaroxaban recipients, and warfarin and rivaroxaban recipients, the incidence of hospitalization for major bleeding per 1000 person-years was 21.42 vs 55.38, 20.05 vs 42.94, and 49.55 vs 35.79, respectively.

The risk for major bleeding was higher with warfarin vs apixaban initiation (hazard ratio [HR], 2.60; 95% CI, 1.51-4.49), with similar findings for rivaroxaban vs apixaban initiation (HR, 2.15; 95% CI, 1.18-3.94). However, there was no difference in risk observed between warfarin vs rivaroxaban initiation (HR, 0.72; 95% CI, 0.41-1.27).

In secondary analyses, the researchers observed increased risk for major gastrointestinal bleeding in warfarin vs apixaban recipients (HR, 2.99; 95% CI, 1.52-5.9) as well as rivaroxaban vs apixaban recipients (HR, 3.38; 95% CI, 1.57-7.25). Warfarin was also associated with higher risk for composite major bleeding to ischemic stroke when compared with apixaban (HR, 2.28; 95% CI, 1.41-3.39).

Further analysis was performed after stratification by ART use. Compared with apixaban, the risk for major bleeding-associated hospitalization was further increased among patients on ART in both the warfarin (HR, 6.68; 95% CI, 2.78-16.02) and rivaroxaban (HR, 4.83; 95% CI, 2.11-11.08) groups.

Results of sensitivity analyses that used 30- or 90-day as-treated gap periods, excluded patients with recent stroke or bleeding, or excluded patients who changed ART during follow-up were consistent with the main analysis.

Study limitations include the observational design, lack of randomization, insufficient power in the subgroup analysis of patients on ART, and potential lack of applicability to younger HIV populations.

According to the researchers, “[T]his is the first study to investigate comparative safety of oral anticoagulants in the rapidly increasing older adult population with HIV.”

Disclosure: One study author declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

By Jessica Nye, PhD

References:

Quinlan CM, Avorn J, Kesselheim AS, et al. Comparative bleeding risk in older patients with HIV and atrial fibrillation receiving oral anticoagulants. JAMA Intern Med. Published online February 24, 2025. doi:10.1001/jamainternmed.2024.8335