Characterization of the Enrollment of Pregnant and Breastfeeding People in Cardiovascular Randomized Clinical Trials

Background/Objectives: Pregnant and breastfeeding people require special considerations for enrollment in clinical trials. However, the baseline proportion of cardiovascular clinical trials including pregnant and breastfeeding people remains unclear. The objective of this study was to characterize the representation of pregnant and breastfeeding people in cardiovascular randomized clinical trials (RCTs) and to determine whether inclusion has increased following the 2018 removal of pregnancy from the FDA’s “vulnerable population” designation. Methods: We screened eight high-impact general medicine and specialty journals for cardiovascular RCTs published between 1 January 2019 and 31 December 2023. We included RCTs examining pharmacological, behavioral, educational, device, or procedural interventions. We excluded RCTs that recruited exclusively male, pediatric, geriatric, or postmenopausal populations, and those specifically designed for obstetrical populations. We also excluded publications reporting follow-up or subgroup, pooled, or secondary analyses of previously published trials. Data from RCTs were independently extracted in duplicate following the PRISMA guidelines. We examined each RCT for pregnancy and breastfeeding inclusion criteria, rationale for exclusion, and contraception requirements. Results: Of 3764 citations identified, 586 met the inclusion criteria. In total, four (0.7%) RCTs permitted inclusion of pregnant people, 382 (65%) explicitly stated their exclusion, and 200 (34%) did not provide specific enrolment criteria for them. The few studies that explicitly stated exclusion of pregnant people (31/382, 8.1%) provided a rationale. 225 (38%) RCTs explicitly stated exclusion of breastfeeding people, and none explicitly permitted inclusion. There was no significant difference in the proportion of pregnant or breastfeeding people included or excluded from RCTs that began enrollment before 2018 versus after 2018. Conclusions: Pregnant and breastfeeding people are primarily excluded from cardiovascular RCTs, and the justification for their exclusion is rarely provided.