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Risk of Acute Thromboembolic Events With Oral Contraceptive Use

A Systematic Review and Meta-analysis

Peragallo Urrutia, Rachel, MD, MSCR; Coeytaux, Remy R., MD, PhD; McBroom, Amanda J., PhD; Gierisch, Jennifer M., PhD, MPH; Havrilesky, Laura J., MD, MHSc; Moorman, Patricia G., PhD; Lowery, William J., MD; Dinan, Michaela, PhD; Hasselblad, Vic, PhD; Sanders, Gillian D., PhD; Myers, Evan R., MD, MPH

doi: 10.1097/AOG.0b013e3182994c43

OBJECTIVE: To estimate the risk of venous thromboembolism, stroke, or myocardial infarction (MI) associated with the use of oral contraceptive pills (OCPs) and to describe how these risks vary by dose or formulation.

DATA SOURCES: We searched PubMed, Embase, the Cochrane Database of Systematic Reviews, and for studies published from January 1995 through June 2012 that evaluated the association between OCP use and risk of venous thromboembolism, stroke, or MI.

METHODS OF STUDY SELECTION: We reviewed 6,476 citations. We included English-language, controlled studies with human participants reporting a quantitative association between exposure to OCPs and outcomes of venous thromboembolism, stroke, or MI. Two investigators independently reviewed articles for inclusion or exclusion; discordant decisions were resolved by team review and consensus. Random-effects meta-analysis was used to generate summary odds ratios (ORs).

TABULATION, INTEGRATION, AND RESULTS: Fifty studies met inclusion criteria. There were no randomized clinical trials. We found threefold increased odds of venous thromboembolism among current compared with noncurrent OCP users (14 studies; OR 2.97, 95% confidence interval [CI] 2.46–3.59). We found twofold increased odds of ischemic stroke (seven studies; OR 1.90, 95% CI 1.24–2.91). There was no evidence of increased risk of hemorrhagic stroke (four studies; OR 1.03, 95% CI 0.71–1.49) or MI (eight studies; OR 1.34, 95% CI 0.87–2.08).

CONCLUSION: Current use of combined OCPs is associated with increased odds of venous thromboembolism and ischemic stroke but not hemorrhagic stroke or MI.

Combined oral contraceptive pill use is associated with significantly increased risks of venous thromboembolism and ischemic stroke but not hemorrhagic stroke or myocardial infarction.

Department of Obstetrics and Gynecology, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina; and Duke Evidence-based Practice Center, Duke Clinical Research Institute, the Department of Community and Family Medicine, Doctor of Physical Therapy Division, and the Departments of Medicine, Obstetrics and Gynecology, and Biostatistics and Bioinformatics, Duke University School of Medicine, the Center for Health Services Research in Primary Care, Durham Veterans Affairs Medical Center, Duke Cancer Institute, Duke University Health System, and Duke Clinical Research Institute, Durham, North Carolina.

Corresponding author: Rachel Peragallo Urrutia, MD, MSCR, Department of Obstetrics and Gynecology, CB #7570, UNC School of Medicine, Chapel Hill, NC 27599-7570; e-mail:

Financial Disclosure The authors did not report any potential conflicts of interest.

Funded under Contract No. 290-2007-10066-I from the Agency for Healthcare Research and Quality (AHRQ) and the Centers for Disease Control and Prevention (CDC), U.S. Department of Health and Human Services. The authors of this report are responsible for its content. Statements in the report should not be construed as endorsement by AHRQ, CDC, the U.S. Department of Health and Human Services, or the U.S. Department of Veterans Affairs.

The authors thank Liz Wing, MA, for editorial assistance; Kathryn Roth Lallinger, MSLS, and Michael D. Musty, BA, for project coordination; and Megan von Isenburg, MSLS, for help with the literature search and retrieval.

© 2013 by The American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.