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

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.