Apixaban vs rivaroxaban: Is one preferable over the other for AF?

Rivaroxaban was associated with a greater risk of major ischaemic or haemorrhagic events compared with apixaban in elderly patients with atrial fibrillation (AF) — suggesting that apixaban appears to be preferable over rivaroxaban when considering oral anticoagulant choice in these patients, according to a retrospective cohort study.

“No randomized trial data are available to guide the choice among DOACs* for a given patient, because DOACs have not been compared head-to-head in randomized clinical trials,” wrote Drs Enrico Ferro,  Dhruv Kazi, and Peter Zimetbaum from Harvard Medical School, Boston, Massachusetts, US, in a linked editorial. [JAMA 2021;326:2372-2374]

“The authors conclude that for 1000 patient-years of treatment, patients who received rivaroxaban had 2.7 additional strokes and 21.1 additional nonfatal bleeding events compared with patients who received apixaban … suggesting that apixaban is associated with lower bleeding risk and possibly greater thromboembolic protection compared with rivaroxaban,” they pointed out.

The retrospective cohort study included 581,451 AF patients aged ≥65 years (mean age 77.0 years, 50.2 percent women) who were beneficiaries of US Medicare. Participants initiated treatment with rivaroxaban (n=227,572) or apixaban (n=353,879) — either at a standard or reduced dose (23.1 percent) — and were followed up for 4 years. [JAMA 2021;326:2395-2404]

After 474,605 person-years of follow-up, the primary composite outcome of major ischaemic and haemorrhagic events occurred more commonly in patients treated with rivaroxaban than apixaban (16.1 vs 13.4 per 1,000 person-years; adjusted hazard ratio [HR], 1.18, 95 percent confidence interval [CI], 1.12–1.24).

This, according to the authors, was “a difference that was statistically significant.”

Similar findings were also seen when analysing each component of the composite outcome individually.  The risk of both major ischaemic events (8.6 vs 7.6 per 1,000 person-years; HR, 1.12, 95 percent CI, 1.04–1.20) and haemorrhagic events (7.5 vs 5.9 per 1,000 person-years; HR, 1.26, 95 percent CI, 1.16–1.36) were higher in the rivaroxaban group vs the apixaban group; so was fatal extracranial bleeding, which was one of the haemorrhagic events included (1.4 vs 1.0 per 1,000 person-years; HR, 1.41; 95 percent CI, 1.18–1.70).

The risk of primary outcome was increased with rivaroxaban, regardless of whether the patients had the reduced dose (27.4 vs 21.0 per 1,000 person-years; HR, 1.28, 95 percent CI, 1.16–1.40) or the standard dose (13.2 vs 11.4 per 1,000 person-years; HR, 1.13, 95 percent CI, 1.06–1.21).

“Although the incidence of [the primary outcome] was increased for patients receiving rivaroxaban in either dose, both the relative and absolute increase in risk were most pronounced for those with reduced doses, which underscores the importance of anticoagulant choice in this population … whose baseline comorbidity indicated greater susceptibility to differences in anticoagulant efficacy and safety,” the researchers pointed out.

In addition, the risk of secondary outcomes such as nonfatal extracranial bleeding (39.7 vs 18.5 per 1,000 person-years; HR, 2.07) and total mortality (44.2 vs 41.0 per 1,000 person-years; HR, 1.06) were also higher in the rivaroxaban vs the apixaban group.

“Although observational analyses like these are susceptible to confounding, the robustness of the study findings to numerous sensitivity analyses is reassuring,” said the editorialists.

In the absence of head-to-head randomized trial data, they highlighted that this study “represents the largest and most contemporary evidence from clinical settings on the differential effectiveness and safety associated with apixaban and rivaroxaban … [and] may have provided ‘reasonable assurance’ that apixaban is more effective and safer than rivaroxaban for patients with AF.”