Efficacy and Safety of Alirocumab in High-Risk Patients With Clinical Atherosclerotic Cardiovascular Disease and/or Heterozygous Familial Hypercholesterolemia (from 5 Placebo-Controlled ODYSSEY Trials).

Abstract

Patients with previous atherosclerotic cardiovascular disease (ASCVD) and/or heterozygous familial hypercholesterolemia (HeFH) are at high risk of future cardiovascular events. Despite maximally tolerated doses of statins, many patients still have elevated low-density lipoprotein cholesterol (LDL-C) levels. We evaluated the efficacy and safety of alirocumab in patients with ASCVD and/or HeFH on a maximally tolerated dose of statin (rosuvastatin 20 or 40 mg, atorvastatin 40 or 80 mg, or simvastatin 80 mg, or lower doses with an investigator-approved reason) ± other lipid-lowering therapies from 5 placebo-controlled phase 3 trials (52 to 78 weeks). Patients with (n = 2,449) and without (n = 1,050) ASCVD were pooled from the FH I, FH II, HIGH FH, LONG TERM, and COMBO I trials. Patients with HeFH with (n = 575) and without ASCVD (n = 682) were pooled from all trials except COMBO I. High-intensity statins were utilized in 55.7% to 59.0% and in 72.4% to 87.6% of the ASCVD and the HeFH groups, respectively. Efficacy end points included LDL-C percent change from baseline to week 24 stratified by alirocumab dose. Mean baseline demographics and lipid levels were comparable in alirocumab- and placebo-treated patients. LDL-C reductions from baseline at week 24 ranged from 46.6% to 51.3% for alirocumab 75/150 mg and from 54.1% to 61.9% for alirocumab 150 mg in ASCVD and HeFH groups and were sustained for up to 78 weeks. LDL-C reductions with alirocumab were independent of ASCVD and/or HeFH status (interaction p value >0.05). Concordant results were observed for other lipids analyzed. The overall safety in the subgroups analyzed was similar in both treatment arms. Injection-site reactions were observed more frequently with alirocumab versus placebo.

• Authors: Peter A McCullough, Christie M Ballantyne, Santosh K Sanganalmath, Gisle Langslet, Seth J Baum, Prediman K Shah, Andrew Koren, Jonas Mandel, Michael H Davidson
• Journal: The American journal of cardiology (Am J Cardiol) Vol. 121 Issue 8 Pg. 940-948 (04 15 2018) ISSN: 1879-1913 [Electronic] United States
• PMID: 29472008 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Chemical References

• Antibodies, Monoclonal
• Antibodies, Monoclonal, Humanized
• Anticholesteremic Agents
• Cholesterol, LDL
• Hydroxymethylglutaryl-CoA Reductase Inhibitors
• PCSK9 Inhibitors
• Rosuvastatin Calcium
• Atorvastatin
• Simvastatin
• PCSK9 protein, human
• alirocumab

Topics

• Adult
• Aged
• Antibodies, Monoclonal (therapeutic use)
• Antibodies, Monoclonal, Humanized
• Anticholesteremic Agents (therapeutic use)
• Atherosclerosis (blood, complications, drug therapy)
• Atorvastatin (therapeutic use)
• Cholesterol, LDL (blood)
• Clinical Trials, Phase III as Topic
• Coronary Disease (blood, complications, drug therapy)
• Drug Therapy, Combination
• Female
• Heterozygote
• Humans
• Hydroxymethylglutaryl-CoA Reductase Inhibitors (therapeutic use)
• Hypercholesterolemia (blood, complications, drug therapy)
• Hyperlipoproteinemia Type II (blood, complications, drug therapy)
• Male
• Maximum Tolerated Dose
• Middle Aged
• PCSK9 Inhibitors
• Peripheral Arterial Disease (blood, complications, drug therapy)
• Risk
• Rosuvastatin Calcium (therapeutic use)
• Simvastatin (therapeutic use)
• Stroke (blood, complications, drug therapy)
• Treatment Outcome