Conference Coverage

Statins, ACE inhibitors linked to fetal cardiac anomalies



– Women exposed to statin treatment during the first trimester of pregnancy had a doubled rate of delivering neonates with a cardiac anomaly, and a nearly 400% increased rate of delivering a baby with a ventricular septal defect, compared with infants born to unexposed women in a case-control review of nearly 400,000 U.S. births during 2003-2014.

A similar, parallel analysis of the same cohort also showed that exposure to an ACE inhibitor at any time during pregnancy linked with roughly tripled rates of premature delivery, low birth weight, and neonatal cardiac anomaly, compared with unexposed women, Ming-Sum Lee, MD, and her associates reported in two posters presented at the annual meeting of the American College of Cardiology.

Dr. Ming-Sum Lee, a cardiologist with Kaiser Permanente of Southern California in Los Angeles Kaiser Permanente Southern California

Dr. Ming-Sum Lee

The findings from both analyses suggest that women exposed to a statin during the first trimester of pregnancy or to an ACE inhibitor at any time during pregnancy be considered for fetal echocardiography for early diagnosis and management of fetal congenital heart disease, said Dr. Lee, a cardiologist with Kaiser Permanente of Southern California in Los Angeles, and her associates.

For the statin analysis the researchers reviewed data collected from 379,238 singleton pregnancies delivered during January 2003-December 2014 to women who received their health care from Kaiser Permanente of Southern California. The cohort included 280 women who filled at least one prescription for a statin during their first trimester of pregnancy. Half the women received simvastatin, and 37% received lovastatin. The researchers used propensity score matching to identify 1,160 women with no statin exposure who closely matched 279 of the women with statin exposure.

The review showed a 2.1% incidence of fetal cardiac anomalies in the infants born to the unexposed women and a 5.0% rate among the exposed women; the hazard ratio was 2.5, which was statistically significant. More detailed analysis showed that the increased incidence of cardiac anomalies was primarily caused by ventricular septal defects, which occurred at a 4.3% rate among the infants born to exposed mothers, a rate 370% higher than among the unexposed pregnancies. No other types of cardiac anomaly examined showed a significant increase among the exposed infants.

Assessment of links with ACE-inhibitor use focused on 404 women who had exposure to the drug class at any time during pregnancy. The most commonly used drug was lisinopril, by 98% of the women. The researchers compared these links against all the other women with exposure to an ACE inhibitor who delivered in the database without propensity score matching or in general any adjustment for clinical features or comorbidities. The analysis showed premature birth (less than 37 weeks’ gestational age) occurred at a 24% rate among the ACE inhibitor–exposed infants and 8% of the unexposed; low birth weight (less than 2,500 g) occurred in 15% of the exposed infants and in 5% of those not exposed, and any type of cardiac anomaly occurred in 4.5% of the exposed neonates and in 1.4% of the unexposed.

Dr. Lee and her associates reported the results of one adjusted analysis that factored maternal comorbidities into the calculation of the relative risk for delivering a neonate with any cardiac anomaly. After adjustment, the incremental risk linked with ACE inhibitor exposure any time during gestation was a statistically significant 80% increase.

Dr. Lee had no disclosures.

SOURCES: Hekimian A et al. ACC 18, Poster 1124-366. Chintamaneni S et al. ACC 18, Poster 1124-365.

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