Effects of high-density lipoprotein targeting treatments on cardiovascular outcomes: A systematic review and meta-analysis

Eur J Prev Cardiol. 2019 Mar;26(5):533-543. doi: 10.1177/2047487318816495. Epub 2018 Dec 6.

Abstract

Background: The effects of increasing high-density lipoprotein cholesterol on cardiovascular outcomes remain uncertain.

Design: We conducted a meta-analysis to investigate the effects of high-density lipoprotein cholesterol modifiers (niacin, fibrates and cholesteryl ester transfer protein inhibitors) on cardiovascular outcomes.

Methods: Thirty-one randomized controlled trials (154,601 patients) with a follow-up of 6 months or more and a sample size of 100 or more patients were selected using MEDLINE, EMBASE and CENTRAL database (inception January 2018).

Results: High-density lipoprotein cholesterol modifiers had no statistically significant effect on cardiovascular mortality in terms of relative risk (RR) (RR 0.94, 95% confidence interval (CI) 0.89-1.00, P = 0.05, I2 = 13%) or absolute risk (risk difference -0.0001, 95% CI -0.0014, 0.0011, P = 0.84, I2 = 28%). High-density lipoprotein cholesterol modifiers reduced the RR of myocardial infarction (RR 0.87, 95% CI 0.82-0.93, P < 0.001, I2 = 37%). This significant effect was derived by the use of fibrates (RR 0.80, 95% CI 0.73-0.87, P < 0.001, I2 = 22%) and meta-regression analysis showed that this benefit was consistent with an absolute reduction in low-density lipoprotein cholesterol. High-density lipoprotein cholesterol modifiers had no effect on stroke (RR 1.00, 95% CI 0.93-1.09, P = 0.94, I2 = 25%) or all-cause mortality (RR 1.02, 95% CI 0.97-1.08, P = 0.48, I2 = 49%). Meta-regression analyses failed to demonstrate a significant association of pharmacologically increased high-density lipoprotein cholesterol with key endpoints. In studies with background statin therapy, high-density lipoprotein cholesterol modifiers had no statistically significant impact on cardiovascular mortality, myocardial infarction, stroke or all-cause mortality ( P > 0.05).

Conclusion: The use of high-density lipoprotein cholesterol modifying treatments had no significant effect on cardiovascular mortality, stroke or all-cause mortality. The beneficial effect on myocardial infarction was lost when drugs were used with statin therapy.

Keywords: CETP inhibitors; Niacin; fibrates; meta-analysis.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Adult
  • Aged
  • Biomarkers / blood
  • Cardiovascular Diseases / diagnosis
  • Cardiovascular Diseases / mortality
  • Cardiovascular Diseases / prevention & control*
  • Cholesterol Ester Transfer Proteins / antagonists & inhibitors*
  • Cholesterol Ester Transfer Proteins / metabolism
  • Cholesterol, HDL / blood*
  • Dyslipidemias / blood
  • Dyslipidemias / diagnosis
  • Dyslipidemias / drug therapy*
  • Dyslipidemias / mortality
  • Female
  • Humans
  • Hypolipidemic Agents / adverse effects
  • Hypolipidemic Agents / therapeutic use*
  • Male
  • Middle Aged
  • Niacin / adverse effects
  • Niacin / therapeutic use*
  • Randomized Controlled Trials as Topic
  • Risk Assessment
  • Risk Factors
  • Treatment Outcome
  • Up-Regulation

Substances

  • Biomarkers
  • CETP protein, human
  • Cholesterol Ester Transfer Proteins
  • Cholesterol, HDL
  • Hypolipidemic Agents
  • Niacin