Progestin-Only Oral Contraceptives Tied to Cardiac Events in Long QT Syndrome

By Lisa Rapaport

August 19, 2021

(Reuters Health) - Women with long QT syndrome who use progestin-only oral contraceptives without concomitant beta-blockers are at increased risk for cardiac events, a new study suggests.

Researchers examined data on 1,659 women with long QT syndrome, including 370 women (22%) who used oral contraceptives. Among those on oral contraceptives, 212 women (57%) used combination pills, while 77 (21%) took estrogen-only versions, and 81 (22%) took progestin-only pills.

A total of 2,027 cardiac events occurred among the study participants during a cumulative follow-up of 35,797 patient-years, the researchers report in Heart Rhythm.

Women on progestin-only oral contraceptives and not taking beta-blockers had a 2.8-fold higher risk of cardiac events. However, when women on this progestin-only birth control took beta-blockers, they were significantly less likely to experience a cardiac event (HR 0.22).

"We expected oral contraceptives to have an effect on the risk of cardiac events in women with long QT syndrome since estrogen, progesterone and testosterone, modulate the potassium channel that is affected by mutations in long QT syndrome especially," said lead study author Dr. Ilan Goldenberg, a professor and director of the Director of Clinical Cardiovascular Research Center at the University of Rochester in New York.

"We did not expect progestin-only to have such a pronounced negative effect since estrogen was found to have a more negative effect in animal models," Dr. Goldenberg said by email.

The study results suggest that progestin-only oral contraceptives are not safe in women with long QT syndrome unless administered concomitantly with beta-blocker therapy, Dr. Goldenberg said.

"We also believe that women on oral contraceptives of any kind should not be administered to women with type 2 long QT syndrome due to the very high risk of arrhythmic events in this subset," Dr. Goldenberg added.

Study participants were genotyped and 23% had long QT type 2. Among women with type 2 who used progestin-only oral contraceptives, the risk of cardiac events was 8-fold higher without concomitant beta blocker therapy. For these women, estrogen-only oral contraceptives without concomitant beta blockers had a 10-fold increased risk of cardiac events.

One limitation of the study is the potential for women with more severe long QT syndrome to be more likely to be prescribed oral contraceptives to avoid the risks of pregnancy, the study team notes.

It's also possible that women on beta blockers were sicker, and not specifically given these medications for the protective effect against cardiac events related to oral contraceptives, said Dr. Noel Bairey Merz, director of the women's heart health research program and a professor of medicine at Cedars-Sinai Medical Center in Los Angeles.

Still, the results reinforce clinical recommendations against use of progestin-only oral contraceptives for women who have or have risk factors for many cardiovascular disease disorders, Dr. Merz, who wasn't involved in the study, said by email. This is due in part to the high rate of thrombosis, osteopenia and osteoporosis.

Women have other choices for birth control such as intrauterine devices that might be considered as an alternative to oral contraceptives, Dr. Merz said.

SOURCE: Heart Rhythm, online July 30, 2021.