Higher risk of venous thrombosis associated with drospirenone-containing oral contraceptives: a population-based cohort study

Abstract

Background: Combined oral contraceptives are a common method of contraception, but they carry a risk of venous and arterial thrombosis. We assessed whether use of drospirenone was associated with an increase in thrombotic risk relative to third-generation combined oral contraceptives.

Methods: Using computerized records of the largest health care provider in Israel, we identified all women aged 12 to 50 years for whom combined oral contraceptives had been dispensed between Jan. 1, 2002, and Dec. 31, 2008. We followed the cohort until 2009. We used Poisson regression models to estimate the crude and adjusted rate ratios for risk factors for venous thrombotic events (specifically deep vein thrombosis and pulmonary embolism) and arterial thromboic events (specifically transient ischemic attack and cerebrovascular accident). We performed multivariable analyses to compare types of contraceptives, with adjustment for the various risk factors.

Results: We identified a total of 1017 (0.24%) venous and arterial thrombotic events among 431,223 use episodes during 819 749 woman-years of follow-up (6.33 venous events and 6.10 arterial events per 10,000 woman-years). In a multivariable model, use of drospirenone carried an increased risk of venous thrombotic events, relative to both third-generation combined oral contraceptives (rate ratio [RR] 1.43, 95% confidence interval [CI] 1.15-1.78) and second-generation combined oral contraceptives (RR 1.65, 95% CI 1.02-2.65). There was no increase in the risk of arterial thrombosis with drospirenone.

Interpretation: Use of drospirenone-containing oral contraceptives was associated with an increased risk of deep vein thrombosis and pulmonary embolism, but not transient ischemic attack or cerebrovascular attack, relative to second- and third-generation combined oral contraceptives.

Figure 1:

Time trends in the use of various combined oral contraceptives (COCs). In total, 5.0% of women in the study cohort used second-generation agents (4.1% norgestrel and 0.9% levonorgestrel), 73.4% used third-generation agents (22.7% desogestrel, 41.6% gestodene and 9.1% norgestimate), 3.6% used the low-dose gestodene-containing agent, 17.1% used a drospirenone-containing COC, and 0.9% used a COC containing chlormadinone acetate. All but one of the contraceptive agents contained 20–30 μg ethinylestradiol as the estrogenic component; the norgestimate-containing COC contained 35 μg ethinylestradiol.