Direct-Acting Antivirals and the Risk of Arrhythmias and Conduction Disorders in Patients with Chronic Hepatitis C: A French Nationwide Cohort Study

Objective To quantify the risk of arrhythmias and conduction disorders (ACD) in patients receiving direct-acting antiviral (DAA) therapy for hepatitis C. Design All individuals aged 18 to 85 years old treated with DAAs between 01 January 2014 and 31 December 2021 were selected from the French national healthcare database (SNDS). Individuals with a history of ACD were excluded. The primary outcome was the incidence of hospitalization or medical procedure for ACD. Marginal structural models were used to adjust for age, sex, medical comorbidities, and concomitant medications. Results After analyzing 87,589 individuals (median age, 52 years; 60% male) from 01 January 2014 to 31 December 2021, 2131 hospitalizations or medical procedures for ACD were observed over 672,572 person-years (PY) of follow-up. The incidence of ACD was 245/100,000 PY [95% confidence interval (CI), 228–263/100,000 PY] before DAA and 375/100,000 PY (95% CI 355–395/100,000 PY) after DAA exposure (rate ratio 1.53; 95% CI 1.40–1.68; P < 0.001). The risk of ACD was increased after DAA exposure, compared with the pre-DAA period (adjusted hazard ratio,1.66; 95% CI 1.43–1.93; P < 0.001). The increase in ACD risk was similar among individuals treated with sofosbuvir-based and sofosbuvir-free regimens. Of the 1398 ACD detected after DAA exposure, 30% were hospitalizations for atrial fibrillation, 25% were medical procedures for ACD, and 15% were hospitalizations for atrioventricular blocks. Conclusion A significant increase in the risk of ACD was observed in the population-level cohort of individuals treated with DAAs, regardless of the regimen. Further research is needed to identify patients at risk of ACD, determine cardiac monitoring strategies, and evaluate the need for Holter monitoring after DAA therapy.