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Safety of the Deferral of Coronary Revascularization on the Basis of Instantaneous Wave-Free Ratio and Fractional Flow Reserve Measurements in Stable Coronary Artery Disease and Acute Coronary Syndromes Impact of intravascular ultrasound-guided percutaneous coronary intervention on long-term clinical outcomes in a real world population Intravascular ultrasound-guided vs angiography-guided drug-eluting stent implantation in complex coronary lesions: Meta-analysis of randomized trials Novel percutaneous interventional therapies in heart failure with preserved ejection fraction: an integrative review Consensus from the 5th European Bifurcation Club meeting A Randomized Study of Distal Filter Protection Versus Conventional Treatment During Percutaneous Coronary Intervention in Patients With Attenuated Plaque Identified by Intravascular Ultrasound The Future of Biomarker-Guided Therapy for Heart Failure After the Guiding Evidence-Based Therapy Using Biomarker Intensified Treatment in Heart Failure (GUIDE-IT) Study SGLT-2 Inhibitors and Cardiovascular Risk: An Analysis of CVD-REAL Fluid Volume Overload and Congestion in Heart Failure: Time to Reconsider Pathophysiology and How Volume Is Assessed Nuclear Imaging of the Cardiac Sympathetic Nervous System: A Disease-Specific Interpretation in Heart Failure

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.