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Clinical benefit from pharmacological elevation of high-density lipoprotein cholesterol: meta-regression analysis

F Hourcade-Potelleret1, S Laporte2, V Lehnert1

  • 1F. Hoffmann-La Roche Ltd., Basel, Switzerland.

Heart (British Cardiac Society)
|April 16, 2015
PubMed

Insights

Cholesteryl ester transfer protein (CETP) inhibitors may not reduce coronary heart disease risk, as high-density lipoprotein cholesterol (HDL-C) levels did not correlate with clinical outcomes. HDL-C may not be a reliable marker for cardiovascular events.

Area of Science:

  • Cardiovascular Medicine
  • Pharmacology
  • Epidemiology

Background:

  • Epidemiological studies link higher high-density lipoprotein cholesterol (HDL-C) to lower coronary heart disease (CHD) risk.
  • This association prompted clinical trials of cholesteryl ester transfer protein (CETP) inhibitors.

Purpose of the Study:

  • To evaluate alternative methods for predicting clinical response to CETP inhibitors.
  • To investigate the relationship between HDL-C changes and clinical outcomes in patients treated with HDL-C-raising drugs.

Main Methods:

  • A meta-regression analysis was performed on data from randomized controlled trials of HDL-C-raising drugs (statins, fibrates, niacin).
  • The analysis included 51 trials with 167,311 patients, focusing on secondary prevention with follow-up exceeding one year.

Main Results:

  • No significant association was found between HDL-C changes and the risk of clinical endpoints (myocardial infarction or cardiac death).
  • CETP inhibitor data aligned with this finding (RR: 1.03).
  • Associations varied by drug class; statins and niacin showed a relationship, but it disappeared after adjusting for low-density lipoprotein cholesterol or excluding open trials.

Conclusions:

  • CETP inhibitors may not significantly impact coronary risk.
  • The relationship between HDL-C levels and clinical events appears drug-dependent, limiting HDL-C's utility as a surrogate marker.
  • Alternative markers of HDL function may be more clinically relevant for predicting cardiovascular events.
Abstract

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