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10-Year Coronary Heart Disease Risk Prediction Using Coronary Artery Calcium and Traditional Risk Factors: Derivation in the MESA (Multi-Ethnic Study of Atherosclerosis) With Validation in the HNR (Heinz Nixdorf Recall) Study and the DHS (Dallas Heart Study) Percutaneous Coronary Intervention Readmissions Where Are the Solutions? Translational Perspective on Epigenetics in Cardiovascular Disease Impact of Oxidative Stress on the Heart and Vasculature: Part 2 of a 3-Part Series Spontaneous Coronary Artery Dissection: JACC State-of-the-Art Review Coronary Artery Calcium Progression Is Associated With Coronary Plaque Volume Progression - Results From a Quantitative Semiautomated Coronary Artery Plaque Analysis Impact of Abnormal Coronary Reactivity on Long-Term Clinical Outcomes in Women New AHA/ACC/HRS Guidance on Sudden Cardiac Death Prevention Patient Characteristics Associated With Antianginal Medication Escalation and De-Escalation Following Chronic Total Occlusion Percutaneous Coronary Intervention: Insights From the OPEN CTO Registry 2017 AHA/ACC Clinical Performance and Quality Measures for Adults With ST-Elevation and Non–ST-Elevation Myocardial Infarction: A Report of the American College of Cardiology/American Heart Association Task Force on Performance Measures
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Review ArticleVolume 75, Issue 16, April 2020

JOURNAL：JACC Article Link

Lipid-Modifying Agents, From Statins to PCSK9 Inhibitors: JACC Focus Seminar

D Preiss, JA Tobert, GK Hovingh et al. Keywords: ezetimibe; low-density lipoprotein cholesterol; Mendelian randomization; proprotein convertase subtilisin/kexin type 9; statin

ABSTRACT

Mendelian randomization studies and randomized trials have conclusively demonstrated that lower low-density lipoprotein (LDL) cholesterol results in fewer cardiovascular events. This review describes key stages in the evolution of LDL cholesterol–lowering treatment. Data from over 25 cardiovascular outcome trials confirm that, within a few years, statins lower the relative risk of major atherosclerotic events by about 22% per 38.7 mg/dl (1 mmol/l) reduction in LDL cholesterol, with similar benefit across patient subgroups. Meta-analyses of these trials have established the safety of statins with regard to nonvascular mortality and cancer. Other agents available for prescription include ezetimibe and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, which both reduce major atherosclerotic events in proportion to their effects on LDL cholesterol and have good safety profiles, though PCSK9 inhibitors remain costly. Investigational LDL cholesterol–lowering agents currently being tested in cardiovascular outcome studies are bempedoic acid, an adenosine triphosphate–citrate lyase inhibitor that reduces cholesterol synthesis, and inclisiran, a double-stranded small interfering ribonucleic acid that inhibits PCSK9 synthesis.
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