Analysis Finds Bempedoic Acid Reduces CV Risk, Regardless of Ethnicity

Fatima Rodriguez, MD, MPH

Credit: LinkedIn

Bempedoic acid demonstrated a reduction in cardiovascular events among a population of statin-intolerant Hispanic/Latinx individuals at high cardiovascular risk, a historically under-represented group in cardiovascular outcomes trials.¹

Results from the prespecified, exploratory analysis of the CLEAR Outcomes trial showed bempedoic acid was well-tolerated and efficacious in lowering low-density lipoprotein cholesterol (LDL-C) and reducing cardiovascular risk, regardless of ethnicity.

“Ongoing attention is needed for clinical trial representation, clinical patterns of cardiovascular disease, and optimizing cardiovascular risk management among the growing Hispanic/Latinx population,” wrote the investigative team, led by Fatima Rodriguez, MD, MPH, division of cardiovascular medicine, department of medicine, Stanford University School of Medicine.

Individuals of Hispanic/Latinx ethnicity experience disproportionate burdens of cardiometabolic risk factors and disparities in treatment.² However, these individuals are typically underrepresented in clinical trials, suggesting the effect of social determinants of health on patient outcomes.

Bempedoic acid received a label expansion from the US Food and Drug Administration (FDA) to include the primary and secondary prevention of cardiovascular risk, after initial approval in February 2020 for lowering LDL-C.³ This approval made bempedoic acid the first LDL-lowering non-statin agent to receive a primary prevention indication.

Approval was awarded based on results from the double-blind, randomized, placebo-controlled CLEAR Outcomes trial, enrolling 13,970 participants at high CV risk with statin-intolerance to bempedoic acid.⁴ Results from CLEAR Outcomes showed the use of bempedoic acid was associated with a 13% relative reduction in the primary endpoint of 4-point major adverse cardiovascular events (MACE).

In CLEAR Outcomes, a pre-specified comparison of treatment effects by ethnicity was conducted for the primary endpoint of 4-point MACE. Individuals of Hispanic/Latinx ethnicity comprised 17% of the study population, including 1190 randomized to bempedoic acid and 1143 randomized to placebo.¹

Compared with the rest of the study population, more Hispanic/Latinx participants were women (56% vs. 47%), enrolled for primary prevention (33% vs. 29%), had more diabetes (61% vs. 43%), had more statin use (29% vs. 21%), had lower ezetimibe use (7% vs. 12%), and had a higher median hsCRP (2.7 vs. 2.2 mg/L).

Upon analysis, the 6-month least-squares placebo-corrected LDL-C change from baseline (–21.0% [95% CI, –23.0 to –19.0] and –21.2% [95% CI, –22.1 to –20.2]) and placebo-corrected absolute LDL-C change from baseline –27.2 mg/dL [95% CI, –29.8 to –24.5] and –29.7 [95 %CI, –30.9 to –28.4]) were similar in Hispanic/Latinx and non-Hispanic/Latinx participants, respectively.

Moreover, compared with placebo, bempedoic acid lowered MACE risk in Hispanic/Latinx participants (85 events [7.1%] vs. 106 events [9.3%]; hazard ratio [HR], 0.77 [95% CI, 0.58 - 1.02]) and in non-Hispanic/Latinx participants (734 events [12.7%] vs. 821 [14.1%]; HR, 0.89 [95% CI, 0.80 - 0.98]) (P = .35).

After adjustment for covariates, including age, sex, region, race, and comorbidities, investigators confirmed the treatment effect homogeneity between ethnicities. Safety data reported serious adverse events in 15% of Hispanic/Latinx participants and 27% of non-Hispanic/Latinx participants receiving bempedoic acid.

In particular, the incidence of specific adverse events, consisting of hyperuricemia, tendon rupture, and renal impairment, were similar between ethnicity groups, reflecting findings from the overall study population.

Overall, Rodriguez and colleagues noted the CLEAR Outcomes trial enrolled a significant amount of Hispanic/Latinx participants, compared with other cardiovascular outcome trials. Evidence has pointed to the high prevalence of dyslipidemia and increased CV risk among Hispanic/Latinx individuals, but patients often remain unaware of their risk and do not receive treatment.

“Hispanic/Latinx individuals are less likely to be prescribed statins and to adhere to this treatment long-term for reasons including statin-intolerance and concern for statin-associated side-effects,” investigators wrote. “This study suggests bempedoic acid is an effective non-statin alternative for lowering LDL-C and CV risk across both Hispanic/Latinx and non-Hispanic/Latinx populations.”

References

1. _{Rodriguez F, Cho L, Foody J, et al. Characteristics and Outcomes for Hispanic/Latinx Participants with Statin-Intolerance Receiving Bempedoic Acid. J Am Coll Cardiol. Published online March 21, 2024. doi:10.1016/j.jacc.2024.03.390}
2. _{Sarraju A, Valencia A, Knowles JW, Maron DJ, Rodriguez F. Diverse Racial/Ethnic Group Underreporting and Underrepresentation in High-Impact Cholesterol Treatment Trials. Circulation. 2021;143(24):2409-2411. doi:10.1161/CIRCULATIONAHA.120.050034}
3. _{Campbell P. Bempedoic acid wins FDA approval for reducing cardiovascular risk in primary, secondary prevention. HCP Live. March 22, 2024. Accessed March 29, 2024. https://www.hcplive.com/view/bempedoic-acid-wins-fda-approval-for-reducing-cardiovascular-risk-reduction-in-primary-secondary-prevention.}
4. _{Campbell P. Bempedoic acid reduces risk of mace by 13% but proves no benefit on cardiovascular death. HCP Live. March 4, 2023. Accessed March 29, 2024. https://www.hcplive.com/view/bempedoic-acid-reduces-risk-of-mace-by-13-but-proves-no-benefit-on-cardiovascular-death.}