https://immattersacp.org/weekly/archives/2023/05/23/1.htm

Amiodarone increases bleeding compared with flecainide or sotalol in patients on anticoagulant therapy

A retrospective analysis of Medicare patients who started an anticoagulant and then amiodarone found that they had a 44% increased risk for bleeding-related hospitalization compared to those on other antiarrhythmics and that this risk was higher with rivaroxaban than apixaban.


Older adults with atrial fibrillation who were treated with amiodarone during apixaban or rivaroxaban use had a greater risk for bleeding-related hospitalizations compared to those taking flecainide or sotalol, a study found.

Researchers conducted a retrospective cohort study among Medicare beneficiaries ages 65 years or older with atrial fibrillation. All started anticoagulation between January 2012 and November 2018 and then started treatment with antiarrhythmic drugs. The primary outcome was time to bleeding-related hospitalizations, while secondary outcomes included ischemic stroke, systemic embolism, and death with or without evidence of bleeding in the past 30 days. Results were published May 23 by Annals of Internal Medicine.

Of a total of 91,590 patients (mean age, 76.3 years; 52.5% women) beginning anticoagulants and antiarrhythmic drugs, 54,977 took amiodarone and 36,613 took flecainide or sotalol. Risk for bleeding-related hospitalizations was significantly higher with amiodarone (rate difference [RD], 17.5 events per 1,000 person-years [95% CI, 12.0 to 23.0]; hazard ratio [HR], 1.44 [95% CI, 1.27 to 1.63]). Incidence of ischemic stroke or systemic embolism was not significantly different (RD, −2.1 events per 1,000 person-years [95% CI, −4.7 to 0.4]; HR, 0.80 [95% CI, 0.62 to 1.03]).

For patients on amiodarone, the risk for death with recent evidence of bleeding (RD, 9.1 events per 1,000 person-years [95% CI, 5.8 to 12.3]; HR, 1.66 [95% CI, 1.35 to 2.03]) was greater than that for death without bleeding (RD, 5.6 events per 1,000 person-years [95% CI, 0.5 to 10.6]; HR, 1.15 [95% CI, 1.00 to 1.31]) (P=0.003 for the HR comparison). Also among amiodarone patients, use of rivaroxaban was associated with greater incidence of bleeding-related hospitalization (RD, 28.0 events per 1,000 person-years [95% CI, 18.4 to 37.6]) than apixaban (RD, 9.1 events per 1,000 person-years [95% CI, 2.8 to 15.3]) (P=0.001).

The study authors calculated that for every 1,000 person-years of amiodarone treatment, there were an additional 17 bleeding-related hospitalizations, including two major hemorrhagic events, as well as nine deaths with recent evidence of bleeding. They noted that this risk was most pronounced in patients who were receiving rivaroxaban or had known risk factors for hemorrhagic complications of anticoagulant treatment.

“These findings, consistent with pharmacokinetic data and case reports, suggest that bleeding risk should be considered in the management of rhythm-control medications,” the authors wrote.