Certain oral contraceptives elevate cardiac risk in women with long QT syndrome
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Women with long QT syndrome taking progestin-only oral contraceptives were at elevated risk for cardiac events, according to a study presented at Heart Rhythm 2021.
The elevated risk was not observed in women with long QT syndrome taking estrogen-only or estrogen-plus-progestin oral contraceptives, and was pronounced in women taking progestin-only oral contraceptives without concomitant beta-blocker therapy, researchers reported.
“Previous studies have shown that the risk of cardiac events is significantly increased in [long QT syndrome] women after the onset of adolescence, and also during the postpartum and perimenopausal periods,” Ilan Goldenberg, MD, professor of medicine and director of the Clinical Cardiovascular Research Center at the University of Rochester Medical Center, said during a press conference. “In contrast, the risk for cardiac events in [long QT syndrome] males is attenuated after adolescence. Those opposing trends may possibly be due to the effect of sex hormones on the potassium channels that are associated with this inherited arrhythmic disorder.”
Because oral contraceptives have high concentrations of sex hormones, Goldenberg and colleagues evaluated the safety of oral contraceptives according to formulation in women with long QT syndrome.
The study included 1,656 women with long QT syndrome, of whom 22% were taking oral contraceptives, from the Rochester-based LQTS Registry who were followed from September 2010 to March 2021.
The primary outcome was incidence of a new or recurrent cardiac event, including syncope, aborted cardiac arrest, long QT syndrome-related sudden cardiac death and appropriate implantable cardioverter defibrillator shocks.
In a multivariable analysis, compared with women not taking oral contraceptives, women taking progestin-only oral contraceptives had elevated risk for cardiac events (adjusted HR = 2.54; 95% CI, 1.09-5.91; P = .03), but women taking estrogen-only oral contraceptives or combined oral contraceptives did not, Goldenberg said during the press conference.
Women taking beta-blockers had reduced risk for cardiac events (aHR = 0.66; 95% CI, 0.51-0.86; P = .002), he said.
Over 25 years, women taking progestin-only oral contraceptives had greater risk for recurrent cardiac events compared with women taking other types of oral contraceptives (P < .001), he said. Compared with women taking no contraceptives, women taking progestin-only oral contraceptives had a nearly threefold risk for recurrent cardiac events (aHR = 2.86; 95% CI, 1.26-6.54; P = .01) if they were not taking beta-blockers, but not if they were (aHR = 0.54; 95% CI, 0.49-1.14; P = .19; P for interaction = .006), according to the researchers.
The rate of cardiac events per 100 patient-years was approximately double in women taking progestin-only oral contraceptives compared with women taking other or no oral contraceptives in patients not taking beta-blockers, but not in patients taking beta-blockers (aHR for beta-blocker treatment effect = 0.22; 95% CI, 0.07-0.74; P = .01), Goldenberg said during the press conference.
“Progestin-only oral contraceptives are associated with a significant increase in the risk of cardiac events in [long QT syndrome] women without concomitant beta-blocker therapy,” Goldenberg said during the press conference. “That has important implications. If a woman cannot tolerate beta-blockers at optimal dosages, [progestin-only oral contraceptives] should not be administered.”
In addition, women with the LQT2 genotype had elevated risk for cardiac events if they were on any oral contraceptive formulation, so for them, “we should be very cautious of administering any type of oral contraceptive, especially if these women would not be able to tolerate maximal dosages of beta-blockers,” Goldenberg said.
Perspective
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Mina K. Chung, MD
This was an observational study rather than a randomized study, but it has some potential practical implications. Previously, it was thought that the estrogen component of hormonal treatments could increase risk, but in this case progestin-only oral contraceptives were associated with risk, particularly in women with LQT2. The study also supports genotyping of patients with long QT syndrome, as knowing LQTS type can have risk stratification and management implications. It also supports the use of beta-blockers in long QT syndrome.
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Goldenberg I, et al. LBCT03-01. Presented at: Heart Rhythm 2021; July 28-31, 2021 (hybrid meeting).
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