Drug Safety

, Volume 41, Issue 1, pp 77–86 | Cite as

Cardiac Harms of Sofosbuvir: Systematic Review and Meta-Analysis

  • Daniel Caldeira
  • Filipe B. Rodrigues
  • Marta M. Duarte
  • Carmelo Sterrantino
  • Márcio Barra
  • Nilza Gonçalves
  • Fausto J. Pinto
  • Joaquim J. Ferreira
  • João Costa
Systematic Review



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.


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


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).


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.


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 http://www.crd.york.ac.uk/PROSPERO/.



The authors thank the manufacturer of sofosbuvir and Dr. Diana Brainard for providing unpublished safety data from sofosbuvir trials.

Author contributions

DC contributed to the concept and design and wrote the first draft of the manuscript; DC, FBR, MMD, CS, MB, and NG contributed to data acquisition and data analysis. DC, FBR, MMD, CS, MB, NG, FJP, JJF, and JC contributed to interpretation of the data, critically revised the manuscript, and gave final approval of the submitted manuscript. DC is the guarantor.

Compliance with Ethical Standards


This was an academic project not funded by any government or non-government grant.

Conflict of interest

Daniel Caldeira, Filipe B. Rodrigues, Marta M. Duarte, Carmelo Sterrantino, Márcio Barra, Nilza Gonçalves, Fausto J. Pinto, Joaquim J. Ferreira, and João Costa have no conflicts of interest that are directly relevant to the content of this study.

Ethical approval and patient consent

Not required for this type of study.

Supplementary material

40264_2017_586_MOESM1_ESM.pdf (948 kb)
Supplementary material 1 (PDF 948 kb)


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Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  • Daniel Caldeira
    • 1
    • 2
    • 3
  • Filipe B. Rodrigues
    • 1
    • 2
  • Marta M. Duarte
    • 4
  • Carmelo Sterrantino
    • 4
  • Márcio Barra
    • 1
  • Nilza Gonçalves
    • 1
    • 2
  • Fausto J. Pinto
    • 5
  • Joaquim J. Ferreira
    • 1
    • 2
  • João Costa
    • 1
    • 2
    • 4
    • 6
  1. 1.Laboratório de Farmacologia Clínica e Terapêutica, Faculdade de MedicinaUniversidade de LisboaLisboaPortugal
  2. 2.Clinical Pharmacology Unit, Instituto de Medicina MolecularFaculdade de Medicina, Universidade de LisboaLisboaPortugal
  3. 3.Cardiology DepartmentHospital Garcia de OrtaAlmadaPortugal
  4. 4.Center for Evidence-Based Medicine (CEMBE), Faculdade de MedicinaUniversidade de LisboaLisboaPortugal
  5. 5.Cardiology Department, Centro Cardiovascular da Universidade de Lisboa (CCUL), Centro Académico Médico de Lisboa (CAML), Faculdade de MedicinaUniversidade de LisboaLisboaPortugal
  6. 6.Portuguese Collaborating Center of The IberoAmerican Cochrane Network, Faculdade de MedicinaUniversidade de LisboaLisboaPortugal

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