Drospirenone-containing oral contraceptive pills and the risk of venous thromboembolism: a systematic review of observational studies.

Abstract

The effects of fourth-generation drospirenone-containing combined oral contraceptives (COCs) on the risk of venous thromboembolism (VTE) are controversial. To assess the methodological strengths and limitations of the evidence on the VTE risk of these COCs. We searched CINAHL, the Cochrane Library, EMBASE, HealthStar, Medline, and the Science Citation Index. Studies were included if they were cohort and case-control studies, reported a venous thrombotic outcome, had a comparator group, reported an effect measure of the association of interest, and were published in English or French. We assessed study quality using the ROBINS-I tool and assessed the presence of four common sources of bias: prevalent user bias, inappropriate choice of comparator, VTE misclassification, and confounding. Our systematic review included 17 studies. The relative risks of VTE associated with drospirenone- versus second-generation levonorgestrel-containing COCs ranged from 1.0 to 3.3. Based on ROBINS-I, three studies had a moderate risk, ten had a serious risk, and four had a critical risk. Nine studies included prevalent users, four included inappropriate comparators, four had VTE misclassification, and five did not account for two or more important confounding factors. The three highest quality studies had relative risks ranging from 1.0 to 1.57. As a result of the methodological limitations of the individual studies, the VTE risk of drospirenone-containing COCs remains unknown. The highest quality studies suggest there are no or slightly increased harmful effects, but their confidence limits do not rule out an almost doubling of the risk. Systematic review of drospirenone: best studies show no or slightly increased VTE risk (versus levonorgestrel).