Add-on ezetimibe treatment to low-dose statins vs medium-intensity statin monotherapy in coronary artery disease patients with poorly controlled dyslipidemia

Hypertens Res. 2019 Dec;42(12):1923-1931. doi: 10.1038/s41440-019-0308-5. Epub 2019 Aug 13.

Abstract

Although ezetimibe has potential value as an add-on therapy to statins, it is not established whether the addition of ezetimibe to statin therapy is more effective than double-dose statin monotherapy. We conducted a crossover design study. Twenty-one coronary artery disease (CAD) patients whose lipid profiles had not achieved Japanese guideline recommendations (JAS 2017), despite receiving low-dose statin therapy, were divided into two groups. Group A received ezetimibe 10 mg in addition to the baseline dose of statin for the first 3 months and was then switched to monotherapy with a double dose of statin for the next 3 months. Group B first received a double dose of statin for 3 months and was then switched to ezetimibe 10 mg in addition to a baseline dose of statin for the next 3 months. Compared with the baseline, double-dose statin therapy reduced low-density lipoprotein (LDL)-cholesterol (from 118 ± 22 to 104 ± 15 mg/dL, P < 0.05) and malondialdehyde-modified LDL (MDA-LDL) (from 142 ± 35 to 126 ± 24 U/L, P < 0.05) but did not lower high-sensitivity C-reactive protein (hsCRP) (3.02 ± 0.47 and 2.98 ± 0.41 log [ng/ml]). The addition of ezetimibe to a baseline dose of statin further reduced LDL-cholesterol (to 89 ± 15, P < 0.0001) and MDA-LDL (to 114 ± 22 U/L, P < 0.001) and reduced hsCRP (to 2.78 ± 0.38 log (ng/ml), P < 0.05). The changes in the levels of MDA-LDL (R = 0.548, P = 0.010) and hsCRP (R = 0.473, P < 0.05) were significantly correlated with the change in the LDL-cholesterol level after the addition of ezetimibe. Add-on ezetimibe treatment appears superior to double-dose statin therapy in CAD patients with poorly controlled dyslipidemia in terms of reductions in LDL-cholesterol level, lipid peroxidation, and inflammation.

Keywords: Ezetimibe; Inflammation; Low-density lipoprotein-cholesterol; Malondialdehyde-modified-low-density lipoprotein; Oxidative stress.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antihypertensive Agents / administration & dosage
  • Antihypertensive Agents / therapeutic use*
  • C-Reactive Protein / metabolism
  • Cholesterol, LDL / blood
  • Coronary Artery Disease / blood
  • Coronary Artery Disease / complications
  • Coronary Artery Disease / drug therapy*
  • Cross-Over Studies
  • Drug Therapy, Combination
  • Dyslipidemias / blood
  • Dyslipidemias / complications*
  • Ezetimibe / administration & dosage
  • Ezetimibe / therapeutic use*
  • Female
  • Hemodynamics / drug effects
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / administration & dosage
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use*
  • Lipid Peroxidation / drug effects
  • Male
  • Malondialdehyde / pharmacology
  • Middle Aged
  • Oxidative Stress

Substances

  • Antihypertensive Agents
  • Cholesterol, LDL
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Malondialdehyde
  • C-Reactive Protein
  • Ezetimibe