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As a healthcare provider treating statin-intolerant patients, you may find that the CLEAR Outcomes trial provides data to help shape your clinical decisions. The primary endpoint data highlight the potential of nonstatin therapies—like NEXLIZET® and NEXLETOL®—in reducing key cardiovascular events. These findings are promising for high-risk populations, where alternative treatments may be beneficial.
Explore the primary endpoint data below to better understand how these therapies fit into cardiovascular disease prevention. Please see below for full Indication and Important Safety Information.
Nicole A. Ciffone MS, ANP-C, AACC, FNLA
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Explore primary endpoint and primary
prevention subgroup data from the
CLEAR Outcomes trial1
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INDICATION
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NEXLIZET and NEXLETOL are indicated:
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The bempedoic acid component of NEXLIZET and NEXLETOL is indicated to reduce the risk of myocardial infarction and coronary revascularization in adults who are unable to take recommended statin therapy (including those not taking a statin) with:
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established cardiovascular disease (CVD), or
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at high risk for a CVD event but without established CVD.
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NEXLIZET, alone or in combination with other LDL-C lowering therapies, to reduce LDL-C in adults with primary hyperlipidemia, including HeFH.
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NEXLETOL, in combination with other LDL-C lowering therapies, or alone when concomitant LDL-C lowering therapy is not possible, to reduce LDL-C in adults with primary hyperlipidemia, including HeFH.
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IMPORTANT SAFETY INFORMATION
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NEXLIZET and NEXLETOL are contraindicated in patients with a prior hypersensitivity to bempedoic acid or ezetimibe or any of the excipients. Serious hypersensitivity reactions including anaphylaxis, angioedema, rash, and urticaria have been reported.
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See additional Important Safety Information below.
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Review primary prevention data
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NEXLETOL significantly reduced the risk of CV events in primary prevention and secondary prevention patients
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Time to first occurrence of MACE-4 (nonfatal MI, coronary revascularization, nonfatal stroke, or CV death)2,3
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HR, 0.87 (95% CI: 0.79-0.96; P=0.004; NNT=63; 819 vs 927 placebo)
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30% of those enrolled in the CLEAR Outcomes trial with NEXLETOL were primary prevention patients
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Prespecified exploratory analysis of primary prevention patients1
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Time to First Occurrence of MACE-4 in Primary Prevention Patients4,5
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(nonfatal MI, coronary revascularization, nonfatal
stroke, or CV death)
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32% RRR
HR, 0.68
(95% CI: 0.53-0.87; NNT=43)
111 vs 161 placebo
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MACE-36
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(nonfatal MI, nonfatal stroke, or CV death)
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39% RRR
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HR, 0.61
(95% CI: 0.46-0.80;
83 vs 134 placebo)
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Methods4,6
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Although prespecified, this study reports on outcomes in a subgroup within a larger clinical trial. Therefore, the results should be interpreted as hypothesis-generating rather than definitive evidence of benefits.
This exploratory subgroup analysis of primary prevention patients enrolled 2100 patients to bempedoic acid and 2106 patients to placebo. Criteria for primary prevention were based on meeting at least one of the following: presence of either type 1 or 2 diabetes in women older than 65 years or men older than 60 years, Reynolds risk score >30% or SCORE risk score >7.5% over 10 years, or coronary artery calcium score >400 Agatston units at any time in the past. Enrollment of primary prevention patients was capped at 30% of the total population (which included a mixed population of primary prevention and secondary prevention patients).
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Study Limitations4
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This is a secondary analysis of a subpopulation in a larger randomized trial. Such analyses can result in false-positive findings due to the testing of multiple subgroups and may represent the play of chance
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The sample size represented a fraction of the total enrolled population, and the number of events was smaller, resulting in wider confidence intervals
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The inclusion of patients who reported inability to tolerate statins resulted in a high mean baseline LDL-C level. The effects of cholesterol lowering on cardiovascular events in populations with lower pretreatment LDL-C levels was not studied
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The trial selected patients using specific criteria for a high level of risk of a first cardiac event. Whether outcomes would be similar in patients identified using other criteria for an increased risk remains uncertain
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Explore more from the CLEAR
Outcomes trial
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IMPORTANT SAFETY INFORMATION (cont.)
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Hyperuricemia: Bempedoic acid, a component of NEXLIZET and NEXLETOL, may increase blood uric acid levels, which may lead to gout. Hyperuricemia may occur early in treatment and persist throughout treatment, returning to baseline following discontinuation of treatment. Assess uric acid levels periodically as clinically indicated. Monitor for signs and symptoms of hyperuricemia, and initiate treatment with urate-lowering drugs as appropriate.
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Tendon Rupture: Bempedoic acid, a component of NEXLIZET and NEXLETOL, is associated with an increased risk of tendon rupture or injury. Tendon rupture may occur more frequently in patients over 60 years of age, in those taking corticosteroid or fluoroquinolone drugs, in patients with renal failure, and in patients with previous tendon disorders. Discontinue NEXLIZET or NEXLETOL at the first sign of tendon rupture. Consider alternative therapy in patients who have a history of tendon disorders or tendon rupture.
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The most common adverse reactions in the primary hyperlipidemia trials of bempedoic acid, a component of NEXLIZET and NEXLETOL, in ≥2% of patients and greater than placebo were upper respiratory tract infection, muscle spasms, hyperuricemia, back pain, abdominal pain or discomfort, bronchitis, pain in extremity, anemia, and elevated liver enzymes.
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Adverse reactions reported in ≥2% of patients treated with ezetimibe (a component of NEXLIZET) and at an incidence greater than placebo in clinical trials were upper respiratory tract infection, diarrhea, arthralgia, sinusitis, pain in extremity, fatigue, and influenza.
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In the primary hyperlipidemia trials of NEXLIZET, the most commonly reported adverse reactions (incidence ≥3% and greater than placebo) observed with NEXLIZET, but not observed in clinical trials of bempedoic acid or ezetimibe, were urinary tract infection, nasopharyngitis, and constipation.
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The most common adverse reactions in the cardiovascular outcomes trial for bempedoic acid, a component of NEXLIZET and NEXLETOL, at an incidence of ≥2% and 0.5% greater than placebo were hyperuricemia, renal impairment, anemia, elevated liver enzymes, muscle spasms, gout, and cholelithiasis.
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Concomitant use of NEXLIZET or NEXLETOL with greater than 20 mg of simvastatin or 40 mg of pravastatin should be avoided due to the potential for increased risk of simvastatin- or pravastatin-related myopathy.
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Discontinue NEXLIZET or NEXLETOL when pregnancy is recognized unless the benefits of therapy outweigh the potential risks to the fetus. Because of the potential for serious adverse reactions in a breast-fed infant, breastfeeding is not recommended during treatment with NEXLIZET or NEXLETOL.
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Report pregnancies to Esperion Therapeutics, Inc. Adverse Event reporting line at 1-833-377-7633.
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Please see full Prescribing Information for NEXLIZET and NEXLETOL.
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CI=confidence interval; CV=cardiovascular; HeFH=heterozygous familial hypercholesterolemia; HR=hazard ratio; LDL-C=low-density lipoprotein cholesterol; MACE=major adverse cardiovascular event; MI=myocardial infarction; NNT=number needed to treat; RRR=relative risk reduction.
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References: 1. Nissen SE, Lincoff DB, Ray KK, et al. Bempedoic acid and cardiovascular outcomes in statin-intolerant patients. N Engl J Med. 2023;388:1353-1364. 2. NEXLETOL. Prescribing information. Esperion Therapeutics, Inc. 3. Data on file. 1002-043 number needed to treat for MACE-4 (full analysis set). February 2024. 4. Nissen SE, Menon V, Nicholls SJ, et al. Bempedoic acid for primary prevention of cardiovascular events in statin-intolerant patients. JAMA. 2023;330(2):131-140. 5. Nissen SE, Lincoff DB, Ray KK, et al. Bempedoic acid and cardiovascular outcomes in statin-intolerant patients. N Engl J Med. 2023;388(suppl):1353-1364. 6. Nissen SE, Menon V, Nicholls SJ, et al. Bempedoic acid for primary prevention of cardiovascular events in statin-intolerant patients. JAMA. 2023;330(suppl 2):131-140.
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This information is intended only for healthcare professionals in the United States.
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