Date of Graduation

Summer 8-11-2012

Degree Type

Capstone Project

Degree Name

Master of Science in Physician Assistant Studies

First Advisor

Robert P. Rosenow, Pharm.D., O.D.

Second Advisor

Annjanette Sommers PA-C, MS

Abstract

Background: Secondary prevention of coronary events in patients with known CHD and dyslipidemia has traditionally been focused on decreasing LDL-C through the use of statins. However, significant risk remains in individuals whose LDL-C has been optimized but HDL-C remains low. A new class of medications, cholesteryl ester transfer protein inhibitors, is effective at significantly increasing HDL-C and potentially reducing cardiovascular risk in such patients. There are currently three CETP inhibitors being developed, two of which have been studied for safety and efficacy in patients with CHD or risk equivalents: anacetrapib and dalcetrapib. Following the safety concerns of torcetrapib, both study medications have demonstrated that they do not have the same off-target effects as those seen in the ILLUMINATE trial.

Methods: A systematic search of the literature was performed utilizing three databases: MEDLINE, CINAHL, and Evidence-Based Medicine Reviews Multifile. Four double-blind, placebo-controlled clinical trials met the inclusion and exclusion criteria for review.

Results: Anacetrapib demonstrated an impressive 138.1% greater increase in HDL-C, and 39.8% greater reduction in LDL-C as compared to placebo without any differences in tolerability or AEs. Although not a pre-determined end-point, there was a significant reduction in revascularization rates with anacetrapib as compared to placebo as well (8 vs 21). Dalcetrapib was also shown to be safe and effective, although its lipid-modifying effects were significantly less than those seen with anacetrapib. The dal-PLAQUE trial also suggested a potential benefit in reducing atherosclerotic lesions in the carotid arteries. Neither medication was shown to increase blood pressure or cardiovascular morbidity or mortality.

Conclusion: Both anacetrapib and dalcetrapib have established themselves as safe and effective agents for increasing HDL-C, and to a lesser extent decreasing LDL-C. Although short-term data suggests a potential cardioprotective benefit with CETP inhibition, definitive conclusions

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