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Association between the Current Use of Low-Dose Oral Contraceptives and Cardiovascular Arterial Disease: A Meta-Analysis

Department of Internal Medicine (J.-P.B.), Université de Sherbrooke, Sherbrooke, Quebec J1H 5N4, Canada; and Departments of Biostatistics (D.K.M.), Internal Medicine (P.A.E., J.E.N.), and Obstetrics and Gynecology (J.E.N.), Medical College of Virginia, Virginia Commonwealth University, Richmond, Virginia 23298

Address all correspondence and requests for reprints to: Jean-Patrice Baillargeon, M.D., M.Sc., University of Sherbrooke, Endocrine Division, 3001 12th North Avenue, Sherbrooke, Quebec J1H 5N4, Canada. E-mail: jp.baillargeon{at}usherbrooke.ca.

Context: The long-term cardiovascular safety of widely used oral contraceptives (OCs) is still debated, and no meta-analysis assesses the modern use of OCs and the associated cardiovascular risks.

Objective: We aimed to assess the risk of cardiovascular diseases associated with current use of low-dose combined OCs.

Data Sources: All studies published between January 1980 and October 2002 were searched using MEDLINE, BIOSIS, and Scientific Citations.

Study Selection: Original studies were selected independently by two investigators (J.P.B., P.A.E.) based on inclusion criteria: low-dose combined OC (<50 µg of ethinyl-estradiol); more than 10 cases in low-dose users; clear definition of cases; concurrent controls; and control for age. A third investigator (J.E.N.) adjudicated disagreements. From 2715 identified articles, 14 independent studies were included.

Data Extraction: All data were abstracted by one investigator (J.P.B.) in a systematic manner. Classification of OCs and types of exposure were directly abstracted from studies. Current use was defined as use at the time of the event or within 3 months. Only peer-reviewed studies with definition of events as definite or possible, based on prespecified criteria, were included.

Data Synthesis: The summary risk estimates associated with current use of low-dose OCs were 1.84 [95% confidence interval (CI) = 1.38, 2.44] for myocardial infarctions and 2.12 (95% CI = 1.56, 2.86) for ischemic strokes. The overall summary odds ratio for both outcomes was 2.01 (95% CI = 1.63, 2.48). Second generation OCs were associated with a significant increased risk of both myocardial infarction and ischemic stroke events [1.85 (95% CI = 1.03,3.32) and 2.54 (95% CI = 1.96,3.28), respectively]; and third-generation OCs, for ischemic stroke outcome only [2.03 (95% CI = 1.15,3.57)].

Conclusions: In conclusion, a rigorous meta-analysis of the literature suggests that current use of low-dose OCs significantly increases the risk of both cardiac and vascular arterial events, including a significant risk of vascular arterial complications with third generation OCs.

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