Physicians' Academy for Cardiovascular Education

CETP inhibitor increases HDL-C significantly but does not reduce CV outcomes

Evacetrapib and Cardiovascular Outcomes in High-Risk Vascular Disease

Lincoff MA, Nicholls SJ, Riesmeyer JS, et al. - N Engl J Med 2017;376:1933-42

Background

There is an inverse association between HDL-C and cardiovascular (CV) outcomes, but raising HDL-C with cholesteryl ester transfer protein (CETP) inhibitors through modulating the transfer of esterified cholesterol from HDL particles to apoB-containing lipoproteins, has not translated into reduced CV risk so far [1-3]. Torcetrapib, one of the CETP inhibitors, in combination with atorvastatin was associated with higher rates of death and CV events compared with atorvastatin alone, although it increased HDL-C by approximately 70% [4]. Similarly, dalcetrapib did not result in a lower rate of CV events compared with placebo in patients with a recent acute coronary syndrome, although it increased HDL-C by 30% [5].

In this analysis of the ACCELERATE study, the impact on the risk of CV complications or death of adding evacetrapib, another CETP inhibitor, to standard-of-care was evaluated and compared with placebo, in 12,092 patients with high-risk vascular disease.

Main results

Conclusion

In the ACCELERATE study, treatment with evacetrapib compared with placebo was associated with an increase in the HDL-C and a reduction in LDL-C, but not with a reduction of CV outcomes.

References

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Find this article online at NEJM