Review Looks at Trials, Management of LDL-C With PCSK9

Low-density lipoprotein (LDL) lowering with PCSK9 inhibitors may be a good recommendation for high-risk patients with LDL cholesterol (LDL-C) levels 70 mg/dL or more on maximally tolerated oral therapies including statins and ezetimibe, according to a state-of-the-art review article published July 9 in the Journal of the American College of Cardiology.

Robert S. Rosenson, MD, FACC, et al., describe how variants in PCSK9 offer insights into mechanisms regulating LDL levels and provide an update on PCSK9 inhibitors following completion of several clinical outcomes trials. They also address the clinical availability of PCSK9 regarding optimal patient populations, clinical outcomes efficacy and safety of intensive LDL-C lowering.

The authors explain that clinical trials with PCSK9 inhibitors have demonstrated reductions in atherosclerotic cardiovascular events (ASCVD), particularly in patients with recent acute coronary syndrome, multi-vessel coronary artery disease or peripheral arterial disease. They also point out that commonly observed profound reductions in LDL-C to levels less than 25 mg/dL have been accompanied by even larger reductions in ASCVD events, supporting the concept that there may be no lower limit for LDL-C.

Furthermore, the authors note that aggressive LDL-C lowering with fully human PCSK9 monoclonal antibodies has been accompanied by a safety profile superior to that of other classes of agents.

"With the benefits seen in the PCSK9 trials, some have questioned whether there should be an even lower LDL-C target," the authors conclude. However, they add that that evidence from several clinical trials – including IMPROVE-IT, FOURIER and ODYSSEY OUTCOMES – showed "significant reductions in ASCVD events with treatment over statin alone, suggesting that further benefit can be achieved, even among patients whose baseline LDL-C is near 70 mg/dL."

"The next step is to verify the cost effectiveness in various clinical cohorts," said Kim A. Eagle, MD, MACC, editor-in-chief of ACC.org.

Clinical Topics: Acute Coronary Syndromes, Dyslipidemia, Vascular Medicine, Atherosclerotic Disease (CAD/PAD), Lipid Metabolism, Nonstatins, Novel Agents, Statins

Keywords: Hydroxymethylglutaryl-CoA Reductase Inhibitors, Cholesterol, LDL, Peripheral Arterial Disease, Antibodies, Monoclonal, Coronary Artery Disease, Acute Coronary Syndrome, Atherosclerosis, Treatment Outcome


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