According to the EMA's Pharmacovigilance Risk Assessment 2 the risk of arterial thromboembolism (ATE, blood clots in arteries, which can potentially cause a stroke or heart attack) is very low with combined hormonal contraceptives. There is no evidence for a difference in the level of risk between products depending on the type of progestogen.
A Cochrane review [Abstract] 1 included 24 case control studies estimating the risk of myocardial infarction or ischemic stroke in users compared with non-users of different types, doses and generations of combined oral contraception (COC) by a network meta-analysis. COC users were not at increased risk of myocardial infarction or ischemic stroke compared with non-users (OR 1.0, 95% CI 0.9 to 1.0). These ORs were similar for myocardial infarction alone (odds ratio, OR, 0.9, 95% CI 0.8 to 1.0) and ischemic stroke alone (OR 1.0, 95% CI 0.9 to 1.1). The risks did not vary according to the generation of progestagen or according to progestagen type. However, the risk of myocardial infarction or ischemic stroke was only increased in women using COCs containing HASH(0x2fcfe80) 50 µg of estrogen.
A database cohort study 3 included 4 945 088 women aged 15-49 years. 1800 pulmonary embolisms (33 per 100 000 women years), 1046 ischaemic strokes (19 per 100 000 women years), and 407 myocardial infarctions (7 per 100 000 women years) were observed. After adjustment for progestogen and risk factors, the relative risks for women using low dose oestrogen (20 µg v 30-40 µg) were 0.75 (95% CI 0.67 to 0.85) for pulmonary embolism, 0.82 (0.70 to 0.96) for ischaemic stroke, and 0.56 (0.39 to 0.79) for myocardial infarction. After adjustment for oestrogen dose and risk factors, desogestrel and gestodene were associated with statistically significantly higher relative risks for pulmonary embolism (2.16, 1.93 to 2.41 and 1.63, 1.34 to 1.97, respectively) compared with levonorgestrel.
A cohort study 4 (UK Biobank) included 161 017 women who had no cardiovascular disease (CVD) at baseline and reported their OC use. Overall, 131 131 (81.4%) of 161 017 participants reported OC use at baseline. The multivariable-adjusted hazard ratios for OC ever users versus never users were 0.92 (95% CI 0.86 to 0.99) for all-cause death, 0.91 (95% CI 0.87 to 0.96) for incident CVD events, 0.88 (95% CI 0.81 to 0.95) for coronary heart disease, 0.87 (95% CI 0.76 to 0.99) for heart failure, and 0.92 (95% CI 0.84 to 0.99) for atrial fibrillation. However, no significant associations of OC use with CVD death, myocardial infarction, or stroke were observed. Furthermore, the beneficial associations were stronger among participants with longer durations of use (P for trend <0.001).
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