Oral Contraceptive Use and the ECG: Evidence of an Adverse QT Effect on Corrected QT Interval

Background: A prolonged corrected QT (QTc) interval is a marker for an increased risk of sudden cardiac death. We evaluated the relationship between oral contraceptive (OC) use, type of OC, and QTc interval. Methods: We identified 410,782 ECGs performed at Northern California Kaiser Permanente on female patients between 15 and 53 years from January, 1995 to June, 2008. QTwas corrected for heart rate using log-linear regression. OC generation (first, second and third) was classified by increasing progestin androgenic potency, while the fourth generation was classified as antiandrogenic. Results: Among 410,782 women, 8.4% were on OC. In multivariate analysis after correction for comorbidities, there was an independent shortening effect of OCs overall (slope = -0.5 ms; SE = 0.12, P < 0.0002). Users of first and second generation progestins had a significantly shorter QTc than nonusers (P < 0.0001), while users of fourth generation had a significantly longer QTc than nonusers (slope = 3.6 ms, SE = 0.35, P < 0.0001). Conclusion: Overall, OC use has a shortening effect on the QTc. Shorter QTc is seen with first and second generation OC while fourth generation OC use has a lengthening effect on the QTc. Careful examination of adverse event rates in fourth generation OC users is needed.