Article Text

PDF
108 The Observational HDL Hypothesis: A Useful Therapeutic Target? a Meta Analysis of 117,411 Patients in Randomised Controlled Trials
  1. Daniel Keene,
  2. Matthew Shun-Shin,
  3. Clare Price,
  4. Darrel Francis
  1. Imperial College London

Abstract

Background Epidemiological studies have shown HDL to be a prognostic marker. We undertook a meta-analysis to assess the benefit on cardiovascular outcomes for those patients on pharmacological interventions aimed at increasing HDL. Niacin, fibrates and cholesteryl ester transfer protein inhibitors (CETP-I) were identified as agents that raise HDL levels.

Design We conducted a meta-analysis of HDL raising therapies and reported the outcomes on the following events; all-cause mortality, coronary heart disease mortality, non-fatal myocardial infarction (MI) and stroke.

Results 39 trials randomised 117,411 patients to HDL raising therapy or control. All interventions raised HDL.

All-cause mortality was not significantly affected by any pharmacological HDL raising intervention. The reported odds ratios for niacin, fibrates, or CETP-I are (OR), 1.03(95% CI 0.92–1.15 p = 0.59), 0.98(0.89–1.08 p = 0.66), and 1.16(0.93–1.44 p = 0.19) respectively.

None of niacin, fibrates, or CETP-I had a significant effect on CHD mortality, OR 0.93(95% CI 0.76–1.12 p = 0.44), 0.92(0.81–1.04 p = 0.19) and, 1.00(0.80–1.24 p = 0.99) respectively. Likewise for stroke no significant effect was seen for niacin, fibrates or CETP-I, OR 0.96(0.75–1.22 p = 0.72), 1.01(0.90–1.13 p = 0.84) and 1.14(0.90–1.45 p = 0.29) respectively.

Niacin trials conducted prior to the era of routine statin therapy showed a significant reduction in non-fatal MI, OR 0.69(0.56–0.85 p = 0.0004), but with background statin there was no significant effect, OR 0.96(0.85–1.09 p = 0.52).

Fibrates behaved similarly.For non-fatal MI, without background statin OR was 0.78(0.71–0.86 p < 0.00001) but with some or all patients on statin OR was 0.83(0.69–1.01 p = 0.07).

Conclusions No HDL-raising agents reduced all-cause mortality, coronary heart disease mortality, myocardial infarction or stroke in statin treated patients. The observational hypothesis that raising HDL should reduce cardiovascular events appears to be incorrect.

  • Niacin
  • Fibrate
  • CETP Inhibitor

Statistics from Altmetric.com

Request permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.