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

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Abstract

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.

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Authors and Affiliations

  1. Sorbonne Université, INSERM, Institut Pierre Louis d’Épidémiologie et de Santé Publique, IPLESP, Paris, France

    Laurent Lam & Fabrice Carrat

  2. Sorbonne Université, Department of Public Health, Assistance Publique-Hôpitaux de Paris, Hôpital Saint-Antoine, Paris, France

    Fabrice Carrat

  3. Department of Hepatology, Assistance Publique-Hôpitaux de Paris, Hôpital Cochin, Paris, France

    Stanislas Pol

  4. Université de Paris Cité, Paris, France

    Stanislas Pol

  5. Department of Cardiology, Saint Antoine and Tenon Hospital, AP-HP, Sorbonne Université, Paris, France

    Ariel Cohen

  6. Unité INSERM UMRS 1166 Unité de recherche sur les maladies cardiovasculaires et métaboliques, Institut Hospitalo-Universitaire, Institut de Cardiométabolisme et Nutrition (ICAN), Sorbonne Université, Paris, France

    Ariel Cohen

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  1. Laurent Lam
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Corresponding author

Correspondence to Laurent Lam.

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Funding

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

Conflict of Interest

FC reports grants from INSERM-ANRS; personal fees from Sanofi, outside the submitted work. SP has received consulting and lecturing fees from Janssen, Gilead, MSD, Abbvie, Biotest, Shinogui, Viiv, LFB, and grants from Bristol-Myers Squibb, Gilead, Roche and MSD without relation to this manuscript. AC has received research grants from ARS, RESICARD (research nurses), and Boehringer-Ingelheim; and consultant and lecture fees from Amgen, AstraZeneca, Bayer Pharma, BMS-Pfizer alliance, Boehringer-Ingelheim, Daiichi Sankyo, Novartis, and VIFOR. LL has nothing to disclose.

Availability of data and material

Due to the nature of this research based on the French administrative health care database, data that support the findings of this study are not available due to ethical and legal restrictions.

Ethics approval

The authors had permanent access to the SNDS (French decree no. 2021-848). All data were anonymized, and no informed consent was required. The study was approved by INSERM CepiDC and conducted in accordance with the Declaration of Helsinki and the French law on biomedical research. Ethics approval by an ethics committee or institutional review board was not required for this research.

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Author Contributions

LL and FC had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Concept and design: LL and FC. Acquisition, analysis, or interpretation of data: All authors. Drafting of the manuscript: LL. Critical revision of the manuscript for important intellectual content: All authors. Statistical analysis: LL and FC. All authors read and approved the final version of the submission.

Transparency Statement

The lead author affirms that the manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned have been explained.

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Lam, L., Pol, S., Cohen, A. et al. Direct-Acting Antivirals and the Risk of Arrhythmias and Conduction Disorders in Patients with Chronic Hepatitis C: A French Nationwide Cohort Study. Drugs 83, 1207–1213 (2023). https://doi.org/10.1007/s40265-023-01918-0

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