Cochrane for Clinicians

Putting Evidence into Practice

The Risk of MI and Ischemic Stroke with Combined Oral Contraceptives


Am Fam Physician. 2016 Nov 1;94(9):691-692.

Author disclosure: No relevant financial affiliations.

Clinical Question

Do combined oral contraceptives increase the risk of myocardial infarction (MI) and ischemic stroke?

Evidence-Based Answer

The overall risk of MI and ischemic stroke is increased in women who use combined oral contraceptives. The relative risk of MI and ischemic stroke increases as estrogen dose rises, increasing by 60% with doses of 20 mcg and more than doubling when doses of 50 mcg or more are used. Risk of MI and ischemic stroke does not vary with the type or generation of progestin. Physicians should be cautious when prescribing combined oral contraceptives because of the increased risk of MI and ischemic stroke.1 (Strength of Recommendation: B, based on limited-quality evidence from observational studies.)

Practice Pointers

Approximately one in six U.S. women of reproductive age uses combined oral contraceptives,2 and all formulations are equally effective at preventing pregnancy. Although estrogen doses in combined oral contraceptive formulations have decreased over the past half-century to diminish the risk of thrombotic events, ensuring patient safety remains essential.

This Cochrane review included 24 observational studies in a meta-analysis comparing the risk of fatal or nonfatal MI or ischemic stroke between users and nonusers, 18 to 50 years of age, of combined oral contraceptives of varying generations, types, and doses. The generation and type varied according to the progestin included, and the dose varied according to the estrogen formulation. Studies with progestin-only contraceptives, non-oral contraceptives, and postmenopausal women using hormone therapy were excluded. Both previous combined oral contraceptive users and never-users were considered nonusers. No randomized trials that met inclusion criteria were found.

The overall combined risk of MI and ischemic stroke was increased for users of combined oral contraceptives when compared with nonusers (relative risk [RR] = 1.6; 95% confidence interval [CI], 1.3 to 1.9). The risks of MI alone

Author disclosure: No relevant financial affiliations.


1. Roach RE, Helmerhorst FM, Lijfering WM, Stijnen T, Algra A, Dekkers OM. Combined oral contraceptives: the risk of myocardial infarction and ischemic stroke. Cochrane Database Syst Rev. 2015;(8):CD011054.

2. Jones J, Mosher W, Daniels K. Current contraceptive use in the United States, 2006–2010, and changes in patterns of use since 1995. National Health Statistics Report. No. 60, October 18, 2012. Accessed December 19, 2015.

3. Curtis KM, Tepper NK, Jatlaoui TC, et al. U.S. Medical Eligibility Criteria for Contraceptive Use, 2016. MMWR Recomm Rep. 2016;65(RR-3):1–104. Accessed August 24, 2016.

These are summaries of reviews from the Cochrane Library.

This series is coordinated by Corey D. Fogleman, MD, Assistant Medical Editor.

A collection of Cochrane for Clinicians published in AFP is available at



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