Department of Medicine and Surgery, Research Centre on Thromboembolic Disorders and Antithrombotic Therapies, University of Insubria, Varese, Italy.
Oncology Unit, IRCCS Fondazione Salvatore Maugeri, University of Pavia, Pavia, Italy.
Department of Internal Medicine, MC Slotervaart, Amsterdam, The Netherlands.
Unit of Clinical Epidemiology, I.R.C.C.S. Orthopedic Institute Galeazzi, Milan, Italy.
Department of Medicine and Surgery, Research Centre on Thromboembolic Disorders and Antithrombotic Therapies, University of Insubria, Varese, Italy. firstname.lastname@example.org.
U.O. Medicina Interna 1, ASST Settelaghi, Viale Borri, 57, 21100, Varese, Italy. email@example.com.
Direct-acting antiviral drugs (DAAs) were recently approved for treating hepatitis C virus-related chronic hepatitis. As advanced chronic liver disease may predispose patients to thrombotic events, it is still uncertain whether DAAs may influence the actual risk of major arterial and venous thrombotic events. We performed a systematic review to assess the incidence of major vascular events in patients receiving DAAs for HCV chronic hepatitis during phase-III randomized controlled trials (RCTs). Two reviewers identified studies through Pubmed database until October 2015. Reporting and incidence of any vascular events were compared with reporting and incidence of major bleeding, anemia (a prespecified safety outcome) and headache (a common non-prespecified safety outcome). 33 RCTs, encompassing 14,764 patients, were included. Only 13 (39%) and 4 (12%) RCTs provide data on any arterial or venous events, respectively. Occurrence of anemia and headache is reported in all studies. Crude unweighted rate of major arterial events is 0.16% (95% CI 0.10-0.24) of the total included population and 0.47% in those 13 RCTs reporting data. Crude unweighted rate of major venous events is 0.03% of the total included population (95% CI 0.01-0.08) and 0.22% in those four RCTs reporting data. Crude unweighted rate of major bleeding is 0.07% (95% CI 0.03-0.1). Incidence of thrombotic events in HCV patients receiving DAAs may be low, but an incorrect estimation cannot be excluded.