Oral contraceptives containing low- or very low-dose estradiol raised the risks of thrombotic stroke and myocardial infarction by a factor of 1 to 2 in a large Danish cohort study. The results were published in the June 14 issue of the New England Journal of Medicine.
Although these risks were high relative to the nonuse of OCs, the absolute risks of thrombotic stroke and MI remained extremely low, said Dr. Øjvind Lidegaard and his associates at the University of Copenhagen.
"We estimate that among 10,000 women who use desogestrel with ethinyl estradiol at a dose of 20 mg for 1 year, 2 will have arterial thrombosis and 6.8 women ... will have venous thrombosis. Although venous thrombosis is three to four times as frequent as arterial thrombosis among young women, the latter is associated with higher mortality and more serious consequences for survivors. Therefore, these figures should be taken into account when prescribing hormonal contraception," they noted.
Few studies have examined the risks of thrombotic stroke and MI associated with the newer hormonal contraceptives, and those that have examined the issue have produced conflicting results. Dr. Lidegaard and his colleagues assessed this association in a cohort of Danish women aged 15-49 years in 1995 who were followed through 2009.
Among these 1,626,158 study subjects, there were 3,311 first thrombotic strokes and 1,725 first MIs during the 15-year follow-up. The case fatality rates were 1.0% for stroke and 10.8% for MI.
Compared with women who didn’t use hormonal contraceptives, those who used low-dose OCs (30-40 mcg estradiol) had a risk of arterial thrombosis that was 1.3-2.3 times higher, and women who used very-low-dose OCs (20 mcg estradiol) had a risk that was 0.9-1.7 times higher, the investigators said (N. Engl. J. Med. 2012;366:2257-66).
These risks did not vary significantly according to the different types of progestin contained in the OCs.
To put these risk elevations in context, it is useful to note that increasing age raised the risk of arterial thrombosis much more dramatically. The risk of thrombotic stroke was 20 times higher and that of MI was 100 times higher among the oldest study subjects – aged 45-49 years at baseline –compared with the youngest (15-19 years). Several previous studies also have noted the steep rise in thrombotic risk with increasing patient age, the researchers said.
Other hormonal contraceptive products also were assessed in this study. None of the contraceptive products that contained progestin only – such as the levonorgestrel-releasing IUD and subcutaneous implants – raised the risk of thrombotic stroke or MI significantly.
In contrast, contraceptive patches raised the relative risk of thrombotic stroke to 3.15, and vaginal rings raised it to 2.49. "One might expect a higher risk of thrombotic stroke with parenteral administration than with oral administration," Dr. Lidegaard and his associates said.
The number of MIs in these two subgroups of women was too low to allow for reliable estimates of MI risk.
This study was supported by the Danish Heart Association. Dr. Lidegaard reported ties to Bayer Pharma, MSD Denmark, and Theramex. Coinvestigator Ellen Løkkegaard, Ph.D., reported ties to Pfizer.