Is Cholesteryl Ester Transfer Protein Inhibition an Effective Strategy to Reduce Cardiovascular Risk? CETP Inhibition as a Strategy to Reduce Cardiovascular Risk: The Pro Case.

Abstract

There is much current interest in the potential of cholesteryl ester transfer protein (CETP) inhibition as a strategy to reduce the risk of developing atherosclerotic cardiovascular disease (ASCVD). There is also great uncertainty. On the one hand, there is a large body of circumstantial evidence suggesting that inhibition of CETP is antiatherogenic and will protect against the development of ASCVD. On the other hand, 2 human clinical outcome trials with CETP inhibitors have failed. However, as outlined below, because of major problems with these 2 human clinical trials, the hypothesis has not been refuted and it remains unknown whether or not CETP inhibition reduces ASCVD risk. This is something we really need to know. The answer will emerge with the results of 2 large ongoing clinical outcome trials designed to test the hypothesis that CETP inhibition reduces ASCVD risk. Response by Hovingh et al on p 432 There is a possibility that the current level of uncertainty about CETP inhibition may impact adversely on the retention of participants in these ongoing clinical trials and thus reduce their power to provide an answer. We believe that everything possible must be done to ensure that the ongoing clinical outcome trials are allowed to proceed to completion with minimal dropout to provide confidence in the result. The purpose of this article is to summarize the large body of evidence showing that CETP inhibition is protective and that continuation of the ongoing trials to completion is essential. To present this evidence, this article addresses a series of fundamental questions. 1. What exactly is the function of CETP? 2. What is the rationale for inhibiting CETP as a strategy to reduce ASCVD risk? 3. What is the relationship between CETP and atherosclerosis in animal studies? 4. What is the relationship between the genetics and activity of CETP and atherosclerosis …