Are pregnancy‐ and lactation‐related eligibility criteria in cardiovascular clinical trials underpinned by drug safety data?

Aim To quantify the prevalence of pregnancy‐, lactation‐ and reproductive potential‐related eligibility criteria in cardiovascular clinical trials and to evaluate whether they are supported by drug‐specific safety data. Methods We analysed randomized phase 3 and phase 4 cardiovascular clinical trials registered on ClinicalTrials.gov between 1 January 2004 and 31 December 2023. We used a rule‐based natural language processing approach to identify eligibility criteria related to pregnancy, lactation and reproductive potential. In trials evaluating antihypertensive and lipid‐modifying drugs, criteria were assessed against human safety data. Results Among 1346 trials (1 834 685 participants, 37% women), 64% contained pregnancy‐, lactation‐ or reproductive potential‐related eligibility criteria. Pregnancy‐related criteria occurred in 59% of trials, lactation‐related criteria in 41% and reproductive potential‐related criteria in 35%. These criteria frequently overlapped. In the 166 trials evaluating antihypertensive and lipid‐modifying drugs, 133 (80%) excluded pregnant women, with 62% of these exclusions being supported by safety data. The remaining 51 (38%) were unsupported because human safety data were insufficient. For lactation, 9 of 97 exclusions (9%) were supported by safety data, 23 (24%) were unsupported because the drug was considered safe and 65 (67%) were unsupported due to insufficient safety data. Conclusion Pregnancy‐, lactation‐ and reproductive potential‐related eligibility criteria are common in cardiovascular trials. Many exclusions of pregnant or lactating women were not supported by drug‐specific safety data, particularly for lactation. Continued exclusion in the absence of sufficient safety data limits opportunities to generate evidence within the controlled setting of clinical trials, shifting evidence generation to routine clinical practice.