†Safety and Efficacy of Bempedoic Acid in Patients with Hypertension

Abstract

<h3>Lead Author's Financial Disclosures</h3> KCF has received honorarium for consultancy from Amgen, Boehringer Ingelheim, Medtronic, Novartis, and Quantum Genomics. <h3>Study Funding</h3> Esperion Therapeutics, Inc. <h3>Background/Synopsis</h3> Patients with hypercholesterolemia often have hypertension (HTN), further increasing cardiovascular disease risk. Statins may affect blood pressure (BP) due to vascular effects. Bempedoic acid (BA) is an ATP citrate lyase inhibitor that lowers LDL-C. <h3>Objective/Purpose</h3> To investigate the safety and lipid-lowering effect of BA in patients with hypercholesterolemia and comorbid HTN. <h3>Methods</h3> Data were pooled from 4 phase 3 studies; patients were randomized 2:1 to BA or placebo (PBO) for 12-52 weeks. In 2 studies, patients also received moderate- to high-intensity statin, and in 2 studies, patients with statin intolerance received low-dose or no statin. Patients were grouped based on history of HTN, which was treated pharmacologically. Percent change from baseline to week 12 of LDL-C and other lipid parameters, and vital signs and adverse events were assessed. Moreover, in a 6 week 1:1 randomized phase 2 study (NCT02178098), the safety and efficacy of BA were assessed in patients with uncontrolled HTN (BP ≥140/90 and ≤180/110 mmHg) not receiving statins or other lipid-lowering therapies. <h3>Results</h3> Of the 3,623 (2,425 BA, 1,198 PBO) patients included, 78% had a history of HTN. At week 12, the PBO-corrected least squares mean (95% CI) percent change in LDL-C was −19.2% (−20.9, −17.5; P<.0001) in patients with HTN and −20.9% (−24.2, −17.5; P<.0001) in patients without HTN (interaction P=.3697). Results were similar for ApoB levels (−13.0% [−14.5, −11.5; P<.0001] for patients with HTN and −15.3% [−18.0, −12.6; P<.0001] for patients without HTN [interaction P=.1586]). Overall, through 12-52 weeks, the BA safety profile was similar in patients with or without HTN with no clinically meaningful changes in BP. In the phase 2 study (n=143; mean baseline [SD] BP 155/96 [12/6] mmHg), the PBO-corrected LS mean (95% CI) percent change in LDL C was −24.2% (−30.3, −18.1; P<.0001) at week 6. Through 6 weeks of BA treatment, 24-hour ambulatory BP monitoring showed no change from baseline in BP; BA was generally well-tolerated with a consistent safety profile across treatment groups. <h3>Conclusions</h3> Regardless of HTN status, BA was generally well-tolerated and significantly lowered LDL-C with no clinically meaningful BP changes.