52 in 52 – #25: Association of Rivaroxaban vs. Apixaban With Major Ischemic or Hemorrhagic Events in Patients With Atrial Fibrillation

Question: 

Does rivaroxaban compared to apixaban have a stronger association with major ischemic and hemorrhagic events?

PICO

Population:

• Inclusion criteria
  • Age ≥ 65 years old
  • Medicare Parts A, B and D insurance coverage
  • Participants with complete demographic information
  • Patients had to have a prescription for apixaban or rivaroxaban at either:
    • The standard dose (5 mg twice daily for apixaban and 20 mg once daily for rivaroxaban)
    • The reduced dose (2.5 mg twice daily for apixaban and 15 mg once daily for rivaroxaban) for patients with factors likely to in- crease plasma concentrations.
  • The medication was prescribed for atrial fibrillation
  • The medication was prescribed between January 1, 2013 and November 30, 2018
  • During the preceding year, patients had to have continuous enrollment in Medicare and,
  • Patients had to have at least 1 outpatient visit and 1 prescription filled (other than the drug being studied)
  • Patients had to be new users of an outpatient oral anticoagulant
• Exclusion criteria
  • Medicare Advantage Plan (Part C) insurance coverage (cited as having less reliable extractable encounter data)
  • Terminal illness
  • Long-term care facility residency ≥ 30 days
  • Mitral valve stenosis
  • Chronic kidney disease stage 4 or 5 or end-stage (ESRD)
  • Mechanical Heart valve (bovine or other bioprosthetic heart valves were enrolled)
  • Any oral anticoagulant use as an outpatient in the preceding year.
  • A stroke or hospitalization for bleeding the preceding 30 days

Follow-up:

• Patients were followed for 4 years (starting the day after the prescription for the anticoagulant was filled)
  • Follow-up of the patient ended under the following circumstances:
    • A gap of > 30 days was documented (based on prescription filling dates), as this was considered medication discontinuation
    • The patient had a change in anticoagulant dose
    • Patient developed stage 4, 5, or end-stage chronic kidney disease
    • Loss of full Medicare enrollment
    • Occurrence of study outcome or death
    • The study period ended (Nov 30, 2018) or the patient completed 4 years of anticoagulation

Intervention and Comparator:

• Rivaroxaban vs. apixaban

Outcome:

• Rate of major ischemic and hemorrhagic events in the rivaroxaban/apixaban groups
  • 1 vs 13.4 per 1000 person-years
  • Rate difference, 2.7 [95% CI, 1.9- 3.5] – significant
  • Hazard ratio, 1.18 [95% CI, 1.12-1.24] – significant
• Major ischemic events:Aadjusted rate, 6 vs 7.6 per 1000 person-years
  • Rate difference, 1.1 [95% CI, 0.5-1.7] – significant
  • Hazard ratio, 1.12 [95% CI, 1.04-1.20] – significant
• Major Hemorrhagic events
  • Adjusted rate, 5 vs 5.9 per 1000 person-years
  • Rate difference, 1.6 [95% CI, 1.1-2.1] – significant
  • Hazard ratio, 1.26 [95% CI, 1.16-1.36] – significant
• Ischemic stroke
  • Adjusted rate, 3 vs 7.2 per 1000 person-years
  • Rate difference, 1.1 [95% CI, 0.5 – 1.6] – significant
  • Hazard ratio, [95% CI, 1.16-1.36] – significant
• Hemorrhagic stroke
  • Adjusted rate, 5 vs 1.7 per 1000 person-years
  • Rate difference, 0.8 [95% CI, 0.5-1.1] – significant
  • Hazard ratio, 1.48 [95% CI, 1.30-1.70] – significant
• Fatal non-intracranial bleeding
  • Adjusted rate, 4 vs 1.0 per 1000 person-years
  • Rate difference, 0.4 [95% CI, 0.2-0.7] – significant
  • Hazard ratio, 1.41 [95% CI, 1.18-1.70] – significant