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Optimal Strategy for Provisional Side Branch Intervention in Coronary Bifurcation Lesions: 3-Year Outcomes of the SMART-STRATEGY Randomized Trial Effect of low-density lipoprotein cholesterol on the geometry of coronary bifurcation lesions and clinical outcomes of coronary interventions in the J-REVERSE registry Coronary Atherosclerosis T1-Weighed Characterization With Integrated Anatomical Reference: Comparison With High-Risk Plaque Features Detected by Invasive Coronary Imaging Prospective, large-scale multicenter trial for the use of drug-coated balloons in coronary lesions: The DCB-only All-Comers Registry Update on chronic thromboembolic pulmonary hypertension Long-term secondary prevention of cardiovascular disease with a Mediterranean diet and a low-fat diet (CORDIOPREV): a randomised controlled trial Adaptive development of concomitant secondary mitral and tricuspid regurgitation after transcatheter aortic valve replacement Changes in Coronary Plaque Composition in Patients With Acute Myocardial Infarction Treated With High-Intensity Statin Therapy (IBIS-4): A Serial Optical Coherence Tomography Study Active and Passive Vaccination for Pulmonary Arterial Hypertension: A Novel Therapeutic Paradigm Diagnostic Performance of Angiogram-Derived Fractional Flow Reserve: A Pooled Analysis of 5 Prospective Cohort Studies
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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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