Newer oral contraceptives may be associated with higher clot risks
A study using data from 2 large primary care databases in the U.K. looked at oral contraceptive use in younger women who had a first diagnosis of venous thromboembolism.
A new study provides more evidence of a link between newer oral contraceptives and an increased risk of venous thromboembolism (VTE).
The study design involved 2 nested case-control studies with data from 2 large primary care databases of 1,340 practices. Participants were women aged 15 to 49 years with a first diagnosis of VTE in 2001-2013. The study, published May 26 by The BMJ, analyzed 10,562 cases of VTE and found that current exposure to any combined oral contraceptive was associated with increased VTE risk (adjusted odds ratio (OR), 2.97; 95% CI, 2.78 to 3.17) when compared with no exposure in the previous year. Odds ratios were adjusted for smoking status, alcohol consumption, ethnic group, body mass index, comorbidities, and other contraceptive drugs.
The risks of VTE varied among the different types of oral contraceptives. One group of drugs—levonorgestrel (adjusted OR, 2.38; 95% CI, 2.18 to 2.59), norgestimate (adjusted OR, 2.53; 95% CI, 2.17 to 2.96), and norethisterone (adjusted OR, 2.56; 95% CI, 2.15 to 3.06)—had lower risks than the second group of drugs, which included gestodene (adjusted OR, 3.64; 95% CI, 3.00 to 4.43), drospirenone (adjusted OR, 4.12; 95% CI, 3.43 to 4.96), cyproterone (adjusted OR, 4.27; 95% CI, 3.57 to 5.11), and desogestrel (adjusted OR, 4.28; 95% CI, 3.66 to 5.01). (Cyproterone, gestodene, and norethisterone are not available in the United States.) Compared with no exposure in the last year, current exposure to the first group of drugs showed a 2.5 times increased VTE risk, and current exposure to the second group resulted in a roughly 4 times increased risk. The number of extra cases of VTE per year per 10,000 treated women was lowest for levonorgestrel (6; 95% CI, 5 to 7) and norgestimate (6; 95% CI, 5 to 8) and highest for desogestrel and cyproterone (both 14; 95% CI, 11 to 17).
The authors noted that exposure to combined oral contraceptives may have been misclassified—for example, some women may have obtained oral contraceptives from community clinics—and that some of the VTE diagnoses may have been uncertain. However, they concluded that risks of VTE associated with combined oral contraceptives were, with the exception of norgestimate, higher for the newer drugs than for the second-generation drugs.
An accompanying editorial pointed out that the study did not find differences in risk between short- and long-term users of the new oral contraceptives, although there was a suggestion of a differential effect in women taking pills containing levonorgestrel. The editorialist wrote that these findings are consistent with a 2011 study, suggesting that new users of oral contraceptives are not, in general, at a materially increased risk of VTE compared with longer-term users.
“These results, combined with those published in a similar study …, clarify inconsistencies in earlier studies and provide important guidance for the safe prescribing of oral contraceptives,” the editorialist wrote.