Dataset Information

Estimated cardiovascular benefits of bempedoic acid in patients with established cardiovascular disease.

ABSTRACT:

Background and aims

Cardiovascular outcomes trials have demonstrated that lowering low-density lipoprotein cholesterol (LDL-C) reduces the risk for future cardiovascular events. We assessed the potential cardiovascular benefits of bempedoic acid through a simulation study in patients with atherosclerotic cardiovascular disease (ASCVD) and elevated LDL-C.

Methods

The validated SMART prediction model was used to estimate the baseline 10-year risk of three-point major adverse cardiovascular events (cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke) in patients with ASCVD who were enrolled in four Phase 3, randomized, placebo-controlled bempedoic acid studies. The predicted change in 10-year cardiovascular risk associated with bempedoic acid was estimated for each patient based on the Cholesterol Treatment Trialists' model. Data were analyzed in two cohorts: Cohort 1 included mostly patients treated with moderate-high intensity statins, and Cohort 2 included patients who were intolerant of more than low-intensity statin.

Results

A total of 2884 patients were included in Cohort 1 and 226 in Cohort 2. Weighted average baseline 10-year cardiovascular event risk was 26.1% and 31.6% for Cohorts 1 and 2, respectively. The least squares mean percent difference (95% confidence interval (CI) of the predicted absolute change in 10-year cardiovascular event risk with bempedoic acid was -3.3% (-3.7% to -2.9%) for patients in Cohort 1 and -6.0% (-7.7% to -4.3%) for patients in Cohort 2 compared with placebo (p < 0.0001 for both).

Conclusions

Among patients with ASCVD who could potentially benefit from additional LDL-C lowering, our simulation predicted a lower absolute cardiovascular event risk after initiating bempedoic acid as compared with placebo.

SUBMITTER: Gunn LH

PROVIDER: S-EPMC9833227 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature

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Publications

Estimated cardiovascular benefits of bempedoic acid in patients with established cardiovascular disease.

Gunn Laura H LH McKay Ailsa J AJ Feng Amy A Louie Michael J MJ Ballantyne Christie M CM Ray Kausik K KK

Atherosclerosis plus 20220528

<h4>Background and aims</h4>Cardiovascular outcomes trials have demonstrated that lowering low-density lipoprotein cholesterol (LDL-C) reduces the risk for future cardiovascular events. We assessed the potential cardiovascular benefits of bempedoic acid through a simulation study in patients with atherosclerotic cardiovascular disease (ASCVD) and elevated LDL-C.<h4>Methods</h4>The validated SMART prediction model was used to estimate the baseline 10-year risk of three-point major adverse cardiov ...[more]

PMID: 36644205

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Project description:The management of low-density lipoprotein cholesterol (LDL-C) levels is a central strategy for the prevention of atherosclerotic cardiovascular disease. Current United States (2018 American Heart Association/American College of Cardiology/Multisociety) and European (2019 European Society of Cardiology/European Atherosclerosis Society) guidelines endorse statin therapy as the first-line therapy for pharmacologic LDL-C lowering. However, in clinical practice up to 30% of patients report partial or complete intolerance to statin therapy. While the nocebo effect with statins is well described, perceived statin intolerance prevents many patients from achieving LDL-C thresholds associated with clinical benefit. Bempedoic acid is a novel, oral, non-statin lipid-l owering therapy that works by inhibiting adenosine triphosphate-citrate lyase, an enzymatic reaction upstream of 3-hydroxy-3-methylglutaryl coenzyme A reductase in the hepatic cholesterol synthesis pathway. Bempedoic acid confers reduction in LDL-C of ~18% on background statin therapy,~21% in patients with statin intolerance, and ~38% when given in fixed-dose combination with ezetimibe. The CLEAR Outcomes trial, which enrolled high-risk primary and secondary prevention patients with reported statin intolerance and LDL-C levels ≥100 mg/dL, showed that bempedoic acid compared with placebo reduced 4-component major adverse cardiovascular events (MACE) by 13% (hazard ratio 0.87, 95% confidence interval 0.79-0.96). Bempedoic acid also reduced 3-component MACE by 15%, myocardial infarction by 23% and coronary revascularization by 19%. The benefit was even greater in the primary prevention cohort (hazard ratio 0.70, 95% confidence interval 0.55-0.89) for 4-component MACE. Bempedoic acid was associated with increases in uric acid levels and cholelithiasis, but numerically fewer events of myalgia and new-onset diabetes. These findings confirm that bempedoic acid is an effective approach to reduce cardiovascular outcomes in high-risk patients with statin intolerance who require further reduction in LDL-C.

Project description:ImportanceThe effects of bempedoic acid on cardiovascular outcomes in statin-intolerant patients without a prior cardiovascular event (primary prevention) have not been fully described.ObjectiveTo determine the effects of bempedoic acid on cardiovascular outcomes in primary prevention patients.Design, setting, and participantsThis masked, randomized clinical trial enrolled 13 970 statin-intolerant patients (enrollment December 2016 to August 2019 at 1250 centers in 32 countries), including 4206 primary prevention patients.InterventionsParticipants were randomized to oral bempedoic acid, 180 mg daily (n = 2100), or matching placebo (n = 2106).Main outcome measuresThe primary efficacy measure was the time from randomization to the first occurrence of any component of a composite of cardiovascular death, nonfatal myocardial infarction (MI), nonfatal stroke, or coronary revascularization.ResultsMean participant age was 68 years, 59% were female, and 66% had diabetes. From a mean baseline of 142.2 mg/dL, compared with placebo, bempedoic acid reduced low-density lipoprotein cholesterol levels by 30.2 mg/dL (21.3%) and high-sensitivity C-reactive protein levels by 0.56 mg/L (21.5%), from a median baseline of 2.4 mg/L. Follow-up for a median of 39.9 months was associated with a significant risk reduction for the primary end point (111 events [5.3%] vs 161 events [7.6%]; adjusted hazard ratio [HR], 0.70 [95% CI, 0.55-0.89]; P = .002) and key secondary end points, including the composite of cardiovascular death, MI, or stroke (83 events [4.0%] vs 134 events [6.4%]; HR, 0.64 [95% CI, 0.48-0.84]; P < .001); MI (29 events [1.4%] vs 47 events [2.2%]; HR, 0.61 [95% CI, 0.39-0.98]); cardiovascular death (37 events [1.8%] vs 65 events [3.1%]; HR, 0.61 [95% CI, 0.41-0.92]); and all-cause mortality (75 events [3.6%] vs 109 events [5.2%]; HR, 0.73 [95% CI, 0.54-0.98]). There was no significant effect on stroke or coronary revascularization. Adverse effects with bempedoic acid included a higher incidence of gout (2.6% vs 2.0%), cholelithiasis (2.5% vs 1.1%), and increases in serum creatinine, uric acid, and hepatic enzyme levels.ConclusionsIn a subgroup of high-risk primary prevention patients, bempedoic acid treatment was associated with reduced major cardiovascular events.Trial registrationClinicalTrials.gov Identifier: NCT02993406.

Project description:BackgroundChronic kidney disease is associated with adverse outcomes among patients with established cardiovascular disease (CVD) or diabetes. Commonly used medications to treat CVD are less effective among patients with reduced kidney function.MethodsREDUCE-IT (Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial) was a multicenter, double-blind, placebo-controlled trial that randomly assigned statin-treated patients with elevated triglycerides (135-499 mg/dL) who had CVD or diabetes and 1 additional risk factor to treatment with icosapent ethyl (4 g daily) or placebo. Patients from REDUCE-IT were categorized by prespecified estimated glomerular filtration rate (eGFR) categories to analyze the effect of icosapent ethyl on the primary end point (composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, coronary revascularization, or unstable angina) and key secondary end point (a composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke).ResultsAmong the 8179 REDUCE-IT patients, median baseline eGFR was 75 mL·min-1·1.73 m-2 (range, 17-123 mL·min-1·1.73 m-2). There were no meaningful changes in median eGFR for icosapent ethyl versus placebo across study visits. Treatment with icosapent ethyl led to consistent reduction in both the primary and key secondary composite end points across baseline eGFR categories. Patients with eGFR <60 mL·min-1·1.73 m-2 treated with icosapent ethyl had the largest absolute and similar relative risk reduction for the primary composite end point (icosapent ethyl versus placebo, 21.8% versus 28.9%; hazard ratio [HR], 0.71 [95% CI, 0.59-0.85]; P=0.0002) and key secondary composite end point (16.8% versus 22.5%; HR 0.71 [95% CI, 0.57-0.88]; P=0.001). The numeric reduction in cardiovascular death was greatest in the eGFR <60 mL·min-1·1.73 m-2 group (icosapent ethyl: 7.6%; placebo: 10.6%; HR, 0.70 [95% CI, 0.51-0.95]; P=0.02). Although patients with eGFR <60 mL·min-1·1.73 m-2 treated with icosapent ethyl had the highest numeric rates of atrial fibrillation/flutter (icosapent ethyl: 4.2%; placebo 3.0%; HR 1.42 [95% CI, 0.86-2.32]; P=0.17) and serious bleeding (icosapent ethyl: 5.4%; placebo 3.6%; HR, 1.40 [95% CI, 0.90-2.18]; P=0.13), HRs for atrial fibrillation/flutter and serious bleeding were similar across eGFR categories (P-interaction for atrial fibrillation/flutter=0.92; P-interaction for serious bleeding=0.76).ConclusionsIn REDUCE-IT, icosapent ethyl reduced fatal and nonfatal ischemic events across the broad range of baseline eGFR categories. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01492361.

Dataset Information

Estimated cardiovascular benefits of bempedoic acid in patients with established cardiovascular disease.

Background and aims

Methods

Results

Conclusions

Publications

Estimated cardiovascular benefits of bempedoic acid in patients with established cardiovascular disease.

Similar Datasets

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