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Derivation, Validation, and Prognostic Utility of a Prediction Rule for Nonresponse to Clopidogrel: The ABCD-GENE Score Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes Use of Intravascular Ultrasound Imaging in Percutaneous Coronary Intervention to Treat Left Main Coronary Artery Disease In acute HF and iron deficiency, IV ferric carboxymaltose reduced HF hospitalizations, but not CV death, at 1 y Poor R-wave progression as a predictor of sudden cardiac death in general population and subjects with coronary artery disease Clinical epidemiology of heart failure with preserved ejection fraction (HFpEF) in comparatively young hospitalized patients Clinical impact of intravascular ultrasound-guided chronic total occlusion intervention with zotarolimus-eluting versus biolimus-eluting stent implantation: randomized study Effects of Dapagliflozin on Symptoms, Function and Quality of Life in Patients with Heart Failure and Reduced Ejection Fraction: Results from the DAPA-HF Trial Relationship between intravascular ultrasound guidance and clinical outcomes after drug-eluting stents: the assessment of dual antiplatelet therapy with drug-eluting stents (ADAPT-DES) study Fractional flow reserve derived from CCTA may have a prognostic role in myocardial bridging

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.