According to the EMA’s Pharmacovigilance Risk Assessment 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 systematic review of seven controlled observational studies (published between 1996 and 2001) on the risk of acute myocardial infarction (MI) among users of second and third generation oral contraceptives (OC) included 6 464 subjects. Four meta-analyses were performed for each of the relevant comparisons. The point estimates for 3gen versus 2gen OC ranged from 0.44 (0.24–0.80) to 0.62 (0.38–0.99). Compared with non-users, the aggregated OR for 3gen OC was 1.13 (0.66–1.92).A Cochrane review 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 ≥ 50 µg of estrogen.
In the early studies published before 1996, a median risk ratio just above 2.0 for any OC then on the market for MI was observed compared with no use. In the review, a pooled OR of 2.18 (1.62–2.94) was determined versus no use since 1996.