In the development program, vericiguat showed embryo-fetal toxicities in animal studies which may be associated with the soluble guanylate cyclase stimulator class. The FDA review team sought information to inform whether a Risk Evaluation and Mitigation Strategies (REMS) program should be required for vericiguat. A retrospective cohort study was conducted in the Sentinel System to assess prevalence of heart failure (HF) in women of childbearing age and the number of live birth pregnancies among these women. A second analysis described characteristics and outcomes of pregnancies in women with HF, and compared them to age-matched pregnant women without HF.
From January 2010 to February 2020, 144,162 women with HF were identified (prevalence, 0.5%) among 29.5 million women of childbearing age in the Sentinel System. Within this HF cohort, there were 813 women with 822 pregnancies ending in live birth deliveries (5.5 deliveries per 1,000 women with HF). Applying the prevalence of HF to the 2019 Census estimates, we projected there were 310,613 women of childbearing with HF in the U.S. in 2019 and among these women, there were an estimated 808 pregnancies ending in live birth deliveries.
In the second analysis, 489 live birth deliveries were identified (mean maternal age, 32.4 years) in 487 women with HF. These women had more comorbidities and used more health services than pregnant women without HF but were healthier than age-matched non-pregnant women with HF. Beta-blockers (21.5%), diuretics (15.3%), and ACE inhibitors (10.2%) were the commonly used HF medications during the pre-pregnancy period. Utilization of beta-blockers remained unchanged throughout and after pregnancy. Use of ACE inhibitors dropped to 5.3% in the first trimester, to less than 1% in the second and third trimesters but increased to 8.0% after pregnancy. Use of other HF medications, such as aldosterone antagonists, angiotensin receptor blockers, and ivabradine, were rare.
HF is rare among women of childbearing age and pregnancies only occurred in a small number of these women. Among women with HF, the use of potentially embryo-fetal toxic HF medications was low and decreased during pregnancy, in accordance with recommendations in drug labeling. Based on the low use of HF medications generally, and the population for which vericiguat is indicated (subtype of HF patients [symptomatic chronic heart failure with reduced ejection), vericiguat exposure is expected to be low. This information contributed to the review team’s determination that labeling would provide sufficient information to ensure the benefits of vericiguat outweigh its risks.