Apixaban Has Edge Over Other OACs for Older HIV Patients With Afib

For people with HIV and atrial fibrillation (Afib or AF), certain oral anticoagulants (OACs) may carry a higher bleeding risk than others, according to a study based on Medicare records.

From a propensity score overlap weighted-analysis, there appeared to be significant differences in the risk of these patients requiring hospitalization for major bleeding over a median 365 days, depending on the OAC they were using:

• Warfarin was associated with more risk than apixaban (Eliquis; 55.38 vs 21.42 per 1,000 person-years, HR 2.60, 95% CI 1.51-4.49), especially in the 71% of patients taking concurrent antiretroviral therapy (ART; HR 6.68, 95% CI 2.78-16.02)
• Rivaroxaban (Xarelto) was also associated with higher risk than apixaban (42.94 vs 20.05 per 1,000 person-years, HR 2.15, 95% CI 1.18-3.94), again with a stronger association in those using ART (HR 4.83, 95% CI 2.11-11.08)
• Risk was comparable between rivaroxaban and warfarin (35.79 vs 49.55 per 1,000 person-years, HR 0.72, 95% CI 0.41-1.27)

“To our knowledge, this is the first study to investigate comparative safety of oral anticoagulants in the rapidly increasing older adult population with HIV,” and it suggests “a superior safety profile for apixaban in this high-risk population,” reported Kueiyu Joshua Lin, MD, SCD, of Brigham and Women’s Hospital, Harvard Medical School, and colleagues in JAMA Internal Medicine.

For this understudied population, the findings may offer some reassurance as apixaban is already the most prescribed OAC in the general population of the U.S. and in people with HIV.

“Prior investigations of OAC effects in older patients with HIV were limited to pharmacokinetic interaction studies of ART with anticoagulants in vitro, as well as limited case reviews and safety reports of individual anticoagulants. Our study is a step toward developing evidence-based clinical guidance to suggest apixaban as a safer choice than warfarin or rivaroxaban in the older AF population with HIV,” the authors wrote.

Lin’s group nevertheless acknowledged that the study was unable to conclude definitively whether there are drug interactions between ART and OACs. One concern is that the metabolism of apixaban and rivaroxaban is thought to be affected by concurrent CYP3A4-, P-glycoprotein-inhibiting ART.

“Clinical guidelines frequently recommend warfarin for any patient receiving protease inhibitor-based, ritonavir-based, or cobicistat-based regimens, despite little evidence of warfarin’s safety in this population,” Lin and colleagues noted. “However, studies have also shown that ART may induce or inhibit the metabolism of warfarin, increasing the risk for drug interactions and causing adverse reactions.”

A caveat of the present study was that around 70% of the cohort had a prescription for concurrent ART on their index day of initiating OAC, which the authors characterized as low.

“Future investigations of reasons why these older patients did not receive ART (e.g., nonadherence, lack of medical access) could help to further explain the observed associations between OAC use and bleeding,” according to Lin’s team. “Larger studies that are sufficiently powered are warranted to confirm possible drug interactions between ART and OACs.”

Outside the scope of this study, there is a flurry of other anticoagulants being developed with the goal of fewer bleeding side effects (albeit not specifically in HIV). These include inhibitors of factor XI, factor XIa, or both, and include oral therapies, monoclonal antibodies, antisense oligonucleotides, and small interfering RNAs.

One injectable anticoagulant with promise is the dual factor XI/XIa inhibitor abelacimab. Being a monoclonal antibody — not metabolized by the cytochrome P-450 system and not a substrate for P-glycoprotein — it poses less risk of drug-drug interactions. Indeed, its strong safety performance in AZALEA-TIMI 71 resulted in the trial being stopped early.

Lin and colleagues based the present study on a national U.S. cohort covered by Medicare fee-for-service. The cohort comprised new initiators of warfarin, rivaroxaban, and apixaban who were ages 50 or older with nonvalvular Afib and HIV.

Lin’s group opted for a target trial emulation framework for the study. With propensity-score overlap weighting, there were separate cohorts available for analysis: warfarin versus apixaban, rivaroxaban versus apixaban, and rivaroxaban versus warfarin.

Baseline covariates were well-balanced between groups after the weighting. Across the three cohorts, average age was around 66 and approximately 21% were women. Mean CHA₂DS₂-VASc scores were just over 3; HAS-BLED scores around 2.

The investigators reported that in line with their primary results, there were more gastrointestinal bleeds with warfarin and rivaroxaban relative to apixaban, the risk especially elevated in ART users.

No differences in the incidence of ischemic stroke or mortality were detected among the three OACs.

Lin and colleagues cautioned that the observational study left room for residual confounding despite statistical adjustments. Additionally, the study of older HIV survivors may not be representative of all people with HIV.

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