Cardiac Harms of Sofosbuvir: Systematic Review and Meta-Analysis

Drug Saf. 2018 Jan;41(1):77-86. doi: 10.1007/s40264-017-0586-2.


Introduction: Sofosbuvir is a new direct-acting pyrimidine nucleotide analogue antiviral drug that has shown remarkable efficacy in the treatment of hepatitis C in clinical trials. However, observational anecdotal data have recently suggested an increased risk of serious bradycardia among patients treated with sofosbuvir and amiodarone.

Objective: We aimed to estimate and characterize the cardiac safety of sofosbuvir by performing a systematic review of randomized controlled trials (RCTs).

Methods: We conducted a systematic review of RCTs (PROSPERO 2016: CRD42016033109) comparing sofosbuvir and non-sofosbuvir regimens in patients with chronic hepatitis C by searching the MEDLINE, Embase, and Cochrane Library databases up to January 2017. Non-published data were obtained from the sofosbuvir marketing authorization holder. Random-effects meta-analysis was performed to derive pooled estimates of relative risks (RRs) and corresponding 95% confidence intervals (CIs).

Results: Six trials, enrolling 2346 patients (1625 treated with sofosbuvir), were included. The overall risk of bias across studies was moderate. The risk of reported cardiac events (RR 0.87; 95% CI 0.41-1.85), arrhythmias (RR 0.93; 95% CI 0.34-2.51), bradycardia (RR 0.47; 95% CI 0.04-5.20), and tachycardia (RR 0.91; 95% CI 0.20-4.20) were not significantly different between sofosbuvir and non-sofosbuvir regimens. The risks of reported syncope, presyncope, loss of consciousness, or palpitations were similar among those receiving sofosbuvir regimens and controls.

Conclusions: The pooled data from RCTs did not show an increased risk of cardiac outcomes, including arrhythmias (and bradycardia), among sofosbuvir-treated patients, although the overall quality of the evidence supporting this conclusion was very low. Registration: PROSPERO 2016:CRD42016033109 at .

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Antiviral Agents / adverse effects*
  • Arrhythmias, Cardiac / chemically induced*
  • Hepatitis C / drug therapy
  • Humans
  • Randomized Controlled Trials as Topic
  • Sofosbuvir / adverse effects*


  • Antiviral Agents
  • Sofosbuvir