Thromboembolism as the adverse event of combined oral contraceptives in Japan

•Incidence rates of thrombosis in Japanese COC users became clear for the first time.•Incidence rates were slightly lower than in people in Western countries.•Almost half of patients developed thrombosis within 90 days after starting COCs.•The mortality rate was estimated to be extremely low.

BackgroundThe risk of thromboembolism associated with combined oral contraceptives (COCs) in Japanese women is not clear yet. The aim of this study is to estimate the current risk of thromboembolism among COC users in Japan.MethodsWe used the Pharmaceuticals and Medical Devices Agency (PMDA) database disclosed by PMDA from April 2004 to December 2013, and extracted thromboembolic events among adverse events from the adverse event information of COC products.ResultsOf the 581 thromboembolic events, venous thromboembolism (VTE) accounted for 394 events, arterial embolism and thrombosis (ATE) were 154, and thrombosis of unspecified sites was 33. In VTE, deep vein thrombosis and pulmonary embolism were the most frequent (78.4%), followed by cerebral vein thrombosis (11.4%). In ATE, cerebral infarction was the most frequent (76.0%) and approximately 6.9-fold higher than coronary heart diseases. The annual estimated incidence per 10,000 person-years of VTE, ATE and all thromboembolisms in current users of all COCs were 1.11 (95% confidence interval: 1.00-1.24), 0.37 (0.30-0.44), and 1.56 (1.42-1.71), respectively. The frequency of all thromboembolic events that developed within 90 days from the start of COCs was 45.5%, and that within 360 days was 81.2%. Sixteen deceased cases were suspected to be associated with thromboembolism, and the estimated mortality rate between 2009 and 2013 was 0.50 (0.30-0.84) per 100,000 person-years.ConclusionsIncidence rates of thromboembolism, particularly VTE, in Japanese current COC users became clear for the first time, being slightly lower than people in Western countries.