Oral contraceptives and risk of cardiac events in women with congenital long-QT syndrome

Women with congenital long-QT syndrome (LQTS) have an increased risk of cardiac events, including sudden cardiac death, after the onset of adolescence, perhaps due to the effects of estrogen and progesterone on cardiac potassium channels.

Use of oral contraceptives may modulate those effects. But a clinical trial presented virtually at Heart Rhythm 2021 found that women with LQTS have an even greater risk of cardiac events by taking progestin-only oral contraceptives without concomitant beta-blocker therapy.

“It is estimated that 1 in 3,000 to 5,000 women in the United States have the syndrome,” said principal investigator Ilan Goldenberg MD, a professor of medicine at the University of Rochester in New York, which has a large registry of LQTS patients.

The investigators of the current study sought to evaluate the safety of oral contraceptives, based on their formulations and sex hormone content.

Beginning in 2010, information on oral contraceptive use, pregnancy, and menopause were obtained from all women enrolled in the Rochester LQTS Registry for a female-specific study. Follow-up through March 21 was reported on 1,656 LQTS women at the meeting.

Of the women, 39% had type LQT1, 35% LQT2 and 14% LQT3.

Overall, 20% of the cohort was treated with an oral contraceptive at any time during follow-up.

For a cumulative follow-up of 35,797 years, there were a total of 1,977 cardiac events from ages 15 through 40 years.

Progestin-only oral contraception was linked to a statistically significant 2.6-fold increased risk of cardiac event in women who did not receive concomitant beta-blocker therapy (P =.01).

Conversely, beta-blocker therapy was highly protective during progestin-only oral contraceptive treatment (P =.01).

However, neither estrogen-only oral contraceptive nor combined (estrogen/progestin) oral contraception was connected to increased cardiac event rates compared to no oral contraception, regardless of beta-blocker treatment.

“The results surprised us because we expected estrogen formulations to be associated with increased risk,” said Goldenberg, who also is director of the Clinical Cardiovascular Research Center at the University of Rochester. “Based on our data, estrogen inhibits the LQTS mutations. It is possible that the study’s findings are related to the fact that most of the contemporary progestin formulations include antiandrogenic components that increase risk.”

Women with LQTS should not be prescribed progestin-only oral contraceptives without concomitant beta-blocker therapy “because their risk of arrhythmic events is very high,” Goldenberg said. “In addition, patients with type 2 LQTS appear to be at an extremely high risk of arrhythmic events, so we believe they should not be prescribed any oral contraceptives.”

Because sudden cardiac death often occurs in patients without structural heart disease and in the absence of other causes, “we hope that studying LQTS as a mechanism of sudden cardiac death will help physicians better understand and treat this patient population,” Goldenberg said.

The study’s findings may have implications for a wider population of patients: those with drug-induced LQTS, caused by common medications like antibiotics and antianxiety pills that affect the ion channel of the heart in a similar mechanism to that of congenital LQTS.

The investigators are currently assessing the effect of oral contraceptive in this population.

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Disclosure

Goldenberg reports no relevant financial disclosures.

Reference

  1. Goldenberg, I. Oral contraceptive use and the risk of cardiac events in women with congenital long QT Syndrome. Presented at: Heart Rhythm 2021; July 28 to 31; virtual.