Reduced-Dose Rivaroxaban Dangerous in Older Patients With Non-Valvular AF

Risk for coronary artery events may be increased by use of reduced-dose rivaroxaban by older patients with non-valvular atrial fibrillation (NVAF), especially for patients aged at least 75 years, according to study findings published in the International Journal of Cardiology.

Investigators aimed to compare efficacy and safety of standard-dose rivaroxaban (15 mg/d) vs non-recommended reduced-dose rivaroxaban (10 mg/d) in patients with NVAF and preserved renal function who are aged at least 65 years.

The investigators conducted a subanalysis of the EXPAND study (ClinicalTrials.gov Identifier: NCT02147444) and assessed the efficacy and safety of rivaroxaban regarding stroke and systemic embolism. EXPAND was a noninterventional observational study from 684 centers across Japan. Rivaroxaban dosage of 15 mg/d or 10 mg/d was at the physician’s discretion.

In the subanalysis, only patients from EXPAND who were aged at least 65 years with a creatinine clearance (CrCl) of 50 mL/min or more were included (ALL cohort; N=3982). This cohort was stratified into the early elderly (ELD) subcohort (65-74 years of age; n=2386) and the late ELD subcohort (at least 75 years of age; n=1444). Subcohorts were further divided into patients who received reduced-dose and patients who received standard-dose groups. Patients in the subanalysis were predominantly men with hypertension. More than 40% had hyperlipidemia and one-quarter had diabetes.

Previous EXPAND subanalysis showed reduced-dose rivaroxaban was associated with lower risk for any bleeding vs standard dose rivaroxaban in a comparison of propensity score-matched dose groups in a population with preserved renal function (CrCl ≥50 mL/min).

There was no difference between dosages in the ALL cohort, early ELD subcohort, or late ELD subcohort in the adjusted hazard ratio (aHR) for incidence of major bleeding. They found no significant between-cohort differences in the occurrence of stroke, systemic embolism, myocardial infarction (MI), and cardiovascular (CV) death or in the occurrence of stroke and systemic embolism.

There were significantly higher occurrence rates for MI/unstable angina, interventional/CV surgery, and CV death with reduced-dose rivaroxaban vs standard-dose rivaroxaban in the ALL cohort (aHR, 1.56; 95% CI, 1.02-2.37; P =.039) and the late ELD subcohort (aHR, 1.86; 95% CI, 1.01-3.42; P =.045) but not in the early ELD subcohort (aHR, 1.20; 95% CI, 0.65-2.23; P =.565).

Limitations of the study include overestimation of the risk for incidence or worsening of coronary artery disease and the underpowered sample size leading to conclusion of no clear benefit of standard-dose rivaroxaban.

“Reduced-dose rivaroxaban in older patients with preserved renal function reduces overall bleeding events, but the benefit gained in terms of major bleeding prevention was not significant…reduced-dose rivaroxaban increased the risk of coronary artery events compared with standard-dose rivaroxaban,” the study authors wrote. “Compared with standard-dose rivaroxaban, reduced-dose rivaroxaban may not adequately prevent CV events or avoid major bleeding in patients with NVAF aged 75 years [or older].”

Disclosure: This research (EXPAND study) was supported by Bayer Yakuhin, Ltd. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.