What is the clinical evidence from this study?

Study design: Review. Population: Cardiovascular disease. Intervention: Cholesteryl ester transfer protein (CETP) inhibitors.

August 3, 2015Open Access

Is Cholesteryl Ester Transfer Protein Inhibition an Effective Strategy to Reduce Cardiovascular Risk?

Key Result

Despite favorable changes in LDL-C and HDL-C, previous clinical trials of CETP inhibitors have failed to reduce cardiovascular events, leaving their efficacy for cardiovascular risk reduction uncertain.

Structured PICO

Does CETP inhibition reduce cardiovascular risk?

Intervention

Cholesteryl Ester Transfer Protein (CETP) inhibitors

Outcome

Cardiovascular risk reduction

CETP inhibitors may reduce cardiovascular risk primarily through substantial LDL-C reduction, despite previous negative trial outcomes and uncertain mechanisms.

Limitations

Animal models may not be representative of human metabolism because mice do not naturally express CETP.
Population studies evaluating CETP levels have highly variable baseline characteristics, lipid levels, and statin use.
Off-target effects, such as blood pressure elevation with torcetrapib, complicate the interpretation of CETP inhibition efficacy.

Abstract

trials with what is known from the Cholesterol Treatment Trialists Collaboration analyses may simply demonstrate that CETPi, if safe, is just another good way to reduce LDL-C (depicted in the Figure ).on the other hand, if the magnitude of benefit is greater than that predicted by LDL-C change, then it would support the notion that the changes in HDL-mediated cholesterol efflux with these drugs are clinically meaningful.The answer might become available sooner than we think. ConclusionsThe lack of consistent data about the consequences of genetically defined CETP deficiency, the uncertain role of CETP in the randomized, controlled trial process, the variability in lipid parameters in patients treated with the different CETPlowering compounds, and the negative outcomes of previous clinical trials all suggest that there are a lot of reasons to think that CETP lowering will not be a CVD-lowering therapy.At the same time, however, the observed substantial reductions in LDL-C with some CETP inhibitors may be sufficient to overcome whatever negative effects CETPi has on other CVD-related parameters.As a consequence, clinicians could be faced with a situation where a drug has opposing effects on CVD-related parameters but with an overall beneficial outcome in terms of CVD risk reduction.

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