Key Points<\/p>\n
Bempedoic acid, an ATP citrate lyase inhibitor, has been shown to reduce LDL cholesterol concentrations by 17% to 28% in clinical trials. However, data on whether bempedoic acid reduces cardiovascular events has been lacking.<\/p>\n
The CLEAR Outcomes trial enrolled 13,970 statin-intolerant individuals at risk for, or with established cardiovascular disease, and randomized them to 180 mg of bempedoic acid per day or placebo.<\/p>\n
Over a median follow-up of 40.6 months, treatment with bempedoic acid resulted in a 13% relative reduction in the composite primary endpoint of CV death, non-fatal myocardial infarction, non-fatal stroke, or coronary revascularization).<\/p>\n
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Musculoskeletal adverse effects are reported among 5-20% of patients prescribed statins in clinical practice resulting in poor adherence or medication discontinuation. Accordingly, non-statin alternatives are an important contribution to the LDL-C lowering armamentarium, particularly for individuals at high-risk for or with established cardiovascular disease. Bempedoic acid, an ATP citrate lyase inhibitor, has been shown to reduce LDL cholesterol concentrations by 17 to 29% in clinical trials, and was approved by the FDA in 2020 for individuals with heterozygous familial hypercholesterolemia or established atherosclerotic cardiovascular disease who require additional lowering of LDL-C as an adjunct to diet and maximally tolerated statin therapy. However, data on whether bempedoic acid reduces cardiovascular events has been lacking.<\/p>\n
<\/p>\n
The Clear Outcomes trial (NCT02993406) was a double-blind, randomized, placebo-controlled trial conduced at 1250 sites in 32 countries which evaluated the effect of 180 mg of bempedoic acid daily on major adverse cardiovascular events (defined as cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, or coronary revascularization) as compared to placebo. The trial enrolled individuals aged 18 years or older deemed at high risk for a cardiovascular event or with established cardiovascular disease. Eligible patients had to be unable or unwilling to receive statins due to an adverse effect (i.e. \u201cstatin-intolerant\u201d). Women who were pregnant or lactating, and individuals with a recent (within 90 days) major cardiovascular event, transient ischemic attack, or unstable or symptomatic arrhythmia were not candidates for the study . A total of 13,970 participants underwent randomization. The mean age of the participants was 65 years, 48% were women, and the majority had a prior cardiovascular event (69.9%). Approximately 23% were taking a statin and 12% were receiving ezetimibe at the time of enrollment. The mean baseline LDL cholesterol concentration was 139 mg\/dl.<\/p>\n
<\/p>\n
The median follow-up was 40.6 months. There was a 21% greater reduction in LDL cholesterol levels with bempedoic acid treatment as compared to placebo at 6 months; the time-averaged difference in LDL cholesterol reduction between the two groups over the course of the trial was 15.9% in favor of bempedoic acid. The primary endpoint occurred in 11.7% participants in the bempedoic acid group and in 13.3% of individuals in the placebo group (hazard ratio, 0.87; 95% CI 0.79 to 0.96; p=0.004). The incidence of the secondary endpoint of three components (cardiovascular death, non-fatal MI, or non-fatal stroke) was also reduced with bempedoic acid as compared to placebo (8.2% vs. 9.5%; hazard ratio, 0.85; 95% CI 0.76 to 0.96; p=0.006). There was no difference in cardiovascular mortality or all-cause mortality between the two groups. There were small absolute increases in the incidence of gout (3.1% vs 2.1%) and cholelithiasis (2.2% vs 1.2%) among individuals treated with bempedoic acid compared to placebo, respectively. The incidence of musculoskeletal adverse events did not differ between the two randomization groups.<\/p>\n
<\/p>\n
The authors noted that these findings establish bempedoic acid as an effective approach to reduce major cardiovascular events in statin intolerant patients.<\/p>\n
<\/p>\n
<\/p>\n","protected":false},"excerpt":{"rendered":"
Key Points Bempedoic acid, an ATP citrate lyase inhibitor, has been shown to reduce LDL cholesterol concentrations by 17% to 28% in clinical trials. However, data on whether bempedoic acid reduces cardiovascular events has been lacking. The CLEAR Outcomes trial enrolled 13,970 statin-intolerant individuals at risk for, or with established cardiovascular disease, and randomized them […]<\/p>\n","protected":false},"author":40603,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[1],"tags":[877,47],"ppma_author":[1029],"class_list":{"0":"post-137800","1":"post","2":"type-post","3":"status-publish","4":"format-standard","6":"category-uncategorized","7":"tag-acc-2023","8":"tag-featured","9":"author-leah-kosyakovsky"},"authors":[{"term_id":1029,"user_id":40603,"is_guest":0,"slug":"leah-kosyakovsky","display_name":"Leah Kosyakovsky","avatar_url":"https:\/\/secure.gravatar.com\/avatar\/864bde69f6f1f80e91e4a97f0a0ba8daa64c2bb702be09ed787444c7dfa045bb?s=96&r=g","0":null,"1":"","2":"","3":"","4":"","5":"","6":"","7":"","8":""}],"_links":{"self":[{"href":"https:\/\/cardiologynownews.org\/index.php?rest_route=\/wp\/v2\/posts\/137800","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/cardiologynownews.org\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/cardiologynownews.org\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/cardiologynownews.org\/index.php?rest_route=\/wp\/v2\/users\/40603"}],"replies":[{"embeddable":true,"href":"https:\/\/cardiologynownews.org\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=137800"}],"version-history":[{"count":1,"href":"https:\/\/cardiologynownews.org\/index.php?rest_route=\/wp\/v2\/posts\/137800\/revisions"}],"predecessor-version":[{"id":137801,"href":"https:\/\/cardiologynownews.org\/index.php?rest_route=\/wp\/v2\/posts\/137800\/revisions\/137801"}],"wp:attachment":[{"href":"https:\/\/cardiologynownews.org\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=137800"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/cardiologynownews.org\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=137800"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/cardiologynownews.org\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=137800"},{"taxonomy":"author","embeddable":true,"href":"https:\/\/cardiologynownews.org\/index.php?rest_route=%2Fwp%2Fv2%2Fppma_author&post=137800"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}