Phase I clinical trials for cardiovascular diseases in Europe: analysis of trends, distribution, and regulatory context.

Introduction: Cardiovascular diseases and their major metabolic risk factors remain the leading contributors to morbidity and mortality in Europe. Despite the growing burden of cardiometabolic conditions and the critical role of early-phase research in drug development, the landscape of Phase I clinical trials in this therapeutic area has not been systematically explored in Europe. Methods: We analysed Phase I clinical trials registered on ClinicalTrials.gov from inception to December 2024, focusing on five European countries (France, Germany, Italy, Spain, and the United Kingdom). After applying disease-specific filters and excluding duplicates, device and dietary supplement studies, 488 trials were retrieved. Conditions were classified into 12 ICD-11-based disease groups and into two macro-categories: cardiovascular diseases (CVDs) and cardiovascular risk factors (CVRFs). Results: Of the 488 trials, 35% targeted CVDs and 65% CVRFs. Diabetes mellitus was the most frequently studied condition (48%), followed by obesity (9%) and heart failure (7%). Most trials (84%) were industry-sponsored, with seven companies accounting for one-third of studies. Germany and the United Kingdom conducted the most trials (262 and 170 trials), while Italy the fewest (20). Southern countries focused predominantly on CVDs, whereas northern countries more on CVRFs. Trials involving ATMPs and rare diseases were proportionally more common in Spain and Italy. Overall, 51% of studies enrolled healthy volunteers, though none in Italy. Conclusion: Significant geographic disparities and a declining trend in early-phase cardiometabolic research may weaken Europe's competitiveness in drug development. Strategic investments in infrastructure, regulatory harmonization, and public-private collaboration are needed to reverse the recent trend.