Phase 2b Randomized Trial of the Oral PCSK9 Inhibitor MK-0616.

Background: MK-0616 is an oral macrocyclic peptide inhibitor of proprotein convertase subtilisin/kexin type 9 (PCSK9) in development for the treatment of hypercholesterolemia.

Objectives: This Phase 2b, randomized, double-blind, placebo-controlled, multicenter trial aimed to evaluate the efficacy and safety of MK-0616 in participants with hypercholesterolemia.

Methods: This trial was planned to include 375 adult participants with a wide range of atherosclerotic cardiovascular disease risk.

Long-term safety and efficacy of anacetrapib in patients with atherosclerotic vascular disease.

Aims: REVEAL was the first randomized controlled trial to demonstrate that adding cholesteryl ester transfer protein inhibitor therapy to intensive statin therapy reduced the risk of major coronary events. We now report results from extended follow-up beyond the scheduled study treatment period.

Methods And Results: A total of 30 449 adults with prior atherosclerotic vascular disease were randomly allocated to anacetrapib 100 mg daily or matching placebo, in addition to open-label atorvastatin therapy.

A Multiregional, Randomized Evaluation of the Lipid-Modifying Efficacy and Tolerability of Anacetrapib Added to Ongoing Statin Therapy in Patients With Hypercholesterolemia or Low High-Density Lipoprotein Cholesterol.

This phase 3, multiregional, randomized, double-blind, placebo-controlled study assessed the efficacy/safety profile of anacetrapib added to ongoing therapy with statin ± other lipid-modifying therapies in patients with hypercholesterolemia who were not at their low-density lipoprotein (LDL-C) goal (as per the National Cholesterol Education Program Adult Treatment Panel III guidelines) and in those with low high-density lipoprotein cholesterol (HDL-C). Patients on a stable dose of statin ± other lipid-modifying therapies and with LDL-C ≥70 to <115, ≥100 to <145, ≥130, or ≥160 mg/dl for very high, high, moderate, or low CHD risk or at LDL-C goal (per CHD risk category) with HDL-C ≤40 mg/dl were randomized in a ratio of 1:1 to anacetrapib 100 mg (n = 290) or placebo (n = 293) for 24 weeks, followed by a 12-week off-drug phase. The co-primary end points were % change from baseline in LDL-C and HDL-C and the safety profile of anacetrapib.

Atherothrombotic Risk Stratification and Ezetimibe for Secondary Prevention.

Background: Ezetimibe improves cardiovascular (CV) outcomes in patients stabilized after acute coronary syndrome (ACS) when added to statin therapy. After ACS, patients vary considerably in their risk for recurrent CV events.

Objectives: This study tested the hypothesis that atherothrombotic risk stratification may be useful to identify post-ACS patients who have the greatest potential for benefit from the addition of ezetimibe to statin therapy.