Stroke, embolism, bleeding risk lower with apixaban vs rivaroxaban in nonvalvular AF

Among patients with nonvalvular atrial fibrillation (AF), treatment with apixaban was associated with a lower rate of ischaemic stroke, systemic embolism, and major bleeding compared with rivaroxaban, according to a large study assessing patients in routine care.

Researchers of this retrospective study used data from the Optum Clinformatics database between 28 December 2012 and 1 January 2019 to identity adults with nonvalvular AF newly prescribed* apixaban 5 mg BID (n=59,172) or rivaroxaban 20 mg QD (n=40,706). Propensity score matching led to a study population of 39,351 new users of each drug (mean age 69 years, 40 percent female). Apixaban users were followed up for a mean 288 days, rivaroxaban users for a mean 291 days.

The incidence rate of ischaemic stroke or systemic embolism was lower among patients on apixaban compared with those on rivaroxaban (n=206 vs 251; 6.64 vs 8.01 per 1,000 person-years; hazard ratio [HR], 0.82, 95 percent confidence interval [CI], 0.68–0.98). [Ann Intern Med 2020;doi:10.7326/M19-2522]

Intracranial haemorrhage (ICH) or gastrointestinal (GI) bleeding also occurred at a lower rate among apixaban vs rivaroxaban recipients (12.94 vs 21.92 per 1,000 person-years; HR, 0.58, 95 percent CI, 0.52–0.66). This reduction was primarily driven by the lower incidence of GI bleeding in the apixaban vs rivaroxaban arms (9.35 vs 17.93 per 1,000 person-years; HR, 0.52, 95 percent CI, 0.45–0.59), with a comparable incidence of ICH between groups (3.64 vs 3.95 per 1,000 person-years; HR, 0.91, 95 percent CI, 0.71–1.18). Bleeding due to other causes was also reduced in the apixaban vs rivaroxaban arm (3.09 vs 5.26 per 1,000 person-years; HR, 0.58).

Hepatitis occurred at a similar rate in the apixaban and rivaroxaban arms (13.07 vs 12.34 per 1,000 person-years; HR, 1.05). Vasculitis was slightly less common with apixaban vs rivaroxaban (1.06 vs 1.21 per 1,000 person-years; HR, 0.86), though the researchers suggested the potential for a null effect, given the wide CIs (0.54–1.37).

The main effectiveness and safety findings persisted in an analysis of patients aged >70 years, a group with an elevated prevalence of AF. The rate of ischaemic stroke or systemic embolism was lower with apixaban compared with rivaroxaban (8.29 vs 10.46 per 1,000 person-years; HR, 0.79), as was the rate of GI bleeding and ICH (17.10 vs 30.02 per 1,000 person-years; HR, 0.57).

“[The results suggest that] apixaban may be safer and more effective than rivaroxaban for treating nonvalvular AF,” said the researchers.

Pertaining to the mechanism behind these findings, the researchers referenced a previous study that showed higher trough anti-factor Xa and lower peak anti-factor Xa activity with apixaban compared with rivaroxaban which may account for the lower risk of stroke and systemic embolism, and bleeding risk, respectively. [Clin Pharmacol 2014;6:179-187]

The lack of information on over-the-counter medication prescriptions was a limitation, they noted. They also pointed out that the findings are not representative of long-term outcomes of these two drugs.