Enhancing representation in cardiovascular trials: Lessons from Lp(a)FRONTIERS EXPANSION in United States Black and Hispanic patients with elevated lipoprotein(a) and established atherosclerotic cardiovascular disease

Abstract

Background

Black and Hispanic individuals are disproportionately impacted by elevated levels of lipoprotein(a) [Lp(a)] and atherosclerotic cardiovascular disease (ASCVD). Despite this, these populations are underrepresented in cardiovascular clinical trials. Herein, the strategies aimed to improve minority representation during the study design and recruitment phase of the Lp(a)FRONTIERS EXPANSION trial are described. Baseline characteristics and study attrition to date are also presented.

Methods

Lp(a)FRONTIERS EXPANSION (NCT06267560) is a randomized, double-blind, phase 3b, placebo-controlled trial evaluating pelacarsen in United States (US) Black/African American and/or Hispanic individuals with elevated Lp(a) (≥125 nmol/L) and established ASCVD. Eligible individuals were randomized 2:1 to receive monthly subcutaneous injections of either pelacarsen 80 mg or placebo, for 12 months. Various design and operational strategies were employed to improve enrollment and retention under four key themes: study design, site selection and engagement, enrollment support, and barrier removal.

Results

Overall, 422 patients were randomized to receive pelacarsen or placebo, with enrollment completed 1 year ahead of schedule. Patients were randomized from 103 sites across 21 US states/territories (including Puerto Rico); 8 sites recruited ≥10 patients. At data cut-off (7 October 2025), 64 patients had completed the trial. The mean±standard deviation age was 63.2 ± 9.1 years, 50.7% (214/422) of patients were male, and 68.0% (287/422) identified as Black/African American. Median (Q1, Q3) Lp(a) levels were 110.3 (79.4, 143.7) mg/dL (226.6 [165.8, 299.7] nmol/L).

Conclusion

The Lp(a)FRONTIERS EXPANSION trial suggests that deliberate, culturally tailored design and operational strategies may improve cardiovascular trial participation by US minority populations. Results from Lp(a)FRONTIERS EXPANSION will provide critical insights into the efficacy and safety profile of pelacarsen in treating elevated Lp(a).