Day 3 Coverage, Saturday May 20
CETP Inhibition Outcomes Trials: Is HDL-C a Viable Target?
Peter H. Jones, MD, FNLA
Associate Professor of Medicine Co-director,
For last several decades, the epidemiologic evidence has supported an inverse relationship of HDL cholesterol to cardiovascular disease. The concept of reverse cholesterol transport has supported this protective role of the HDL particle. However, recent genetic studies have cast some doubt on the role of HDL in atheroprotection, and CV outcomes trials with niacin and fenofibrate also failed to confirm an incremental benefit from a strategy to target HDL in high risk patients. Cholesteryl ester transfer protein (CETP) facilitates the neutral lipid exchange of cholesteryl esters for triglycerides between HDL and triglyceride-rich lipoproteins. Inhibition of CETP results in the formation of larger, cholesterol-rich HDL particles, and appears to improve reverse cholesterol transport. Several drugs that inhibit CETP were developed and tested in clinical outcomes trials (torcetrapib, dalcetrapib and evacetrapib), and each failed to demonstrate any benefit in statin-treated patients. This lecture reviewed the data, the lipid effects of CETP inhibition, and whether the final CETP outcomes trial with anacetrapib can provide any hope for this mechanism of targeting HDL. The ultimate answer to whether HDL is a viable target may rest with assessing alternative measures of HDL benefit, such as functionality, rather than just the cholesterol content of the particle.
Coronary Artery Calcium – Refining Risk Estimates and Defining Treatment
Michael J. Blaha, MD, MPH
Director of Clinical Research
Detecting subclinical atherosclerosis with coronary artery calcium (CAC) is remarkably useful for identifying individuals at risk for cardiovascular events, and CAC appears to be the single most robust tool for guiding initiation of appropriate and timely primary prevention strategies. But how does a lipidologist best determine its clinical value?
Fortunately, over the last few years, the research around CAC has matured to include data supporting enhanced clinician-patient risk discussions, shared decision making, specific clinical decision algorithms, flexible risk factor treatment goals, and cost-effectiveness analyses. We have moved from time when we asked “if CAC adds to the risk score” to an era when we are asking “does CAC facilitate a shared decision making model matching risk, intensity of treatment, and patients’ preferences?” The 2015 MESA CHD Risk Score and 2017 guidelines on the use of CAC published by the Society of Cardiovascular Computed Tomography (SCCT) reflect this new approach.
In this presentation, Dr. Blaha reviewed the transition to this more clinically relevant CAC research, arguing for a more routine use of CAC for guiding intensity of lipid lowering (including potentially PCSK9i) in future AHA/ACC and NLA guidelines.