CETP inhibitors, will ever work?

In dal-OUTCOMES, 15,871 patients with acute coronary syndrome was stopped because of no benefit of CETP inhibitors Dalcetrapib 600 mg daily, this dalcetrapib did not show any benefit in reduction of ACS or ischemic stroke or cardiac arrest 8.3% in dalcetrapib group versus 8% in placebo group. However dalcetrapib did reduce HDL –C by 30% without any effect on Triglyceride and LDL-C.

This raises possibility of weather CETP inhibitions will ever succeed in reducing ACS or ischemic stroke. To complicate further dalcetrapib was associated with increase in CRP more than 2mg and blood pressure increase of 0.6mmhg.
Possible explanation for failure of this dalcetrapib could be
1.     In patient who are on statins additional CETP inhibitions may not be advantages(in this study 91% of patients were on statins)
2.     CETP inhibition may produce HDL that may not enhance reverse cholesterol transport.
3.     Dalcetrapib is only a partial CETP inhibitor. (more-potent CETP inhibitors, such as anacetrapib and evacetrapib, may still demonstrate benefit.)
Although Raising the HDL-C did reduce the atherosclerosis in mice with infusion of HDL and purified apoA-1, but these atherosclerosis regression could at least partly explained by antioxidant property of HDL-C may not be by cholesterol excretion by reverse cholesterol transport.

Author: Dr Umesh Bilagi

MBBS, MD, DM (cardiology). I am Interventional cardiologist. Blogging is my passion. Associate professor of cardiology KIMS Hubli. Director and consultant at Tatwadarsha Hospital Hubli. Owner of Jeevan Jyoti Hospital Hubli. Mobile +91 9343403620.

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