Comparative Safety and Efficacy of Low/Moderate-Intensity Statin plus Ezetimibe Combination Therapy vs. High-Intensity Statin Monotherapy in Patients with Atherosclerotic Cardiovascular Disease: An Updated Meta-Analysis

Am J Cardiovasc Drugs. 2024 May;24(3):419-431. doi: 10.1007/s40256-024-00642-8. Epub 2024 Apr 5.

Abstract

Aim: Statin therapy is considered the gold standard for treating hypercholesterolemia. This updated meta-analysis aims to compare the efficacy and safety of a low/moderate-intensity statin in combination with ezetimibe compared with high-intensity statin monotherapy in patients with atherosclerotic cardiovascular disease (ASCVD).

Methods: A systematic search of two databases (PubMed and Cochrane CENTRAL) was conducted from inception to January 2023 and a total of 21 randomized clinical trials (RCTs) were identified and included in the analysis. Data were pooled using Hedges's g and a Mantel-Haenszel random-effects model to derive standard mean differences (SMDs) and 95% confidence intervals (Cis). The primary outcome studied was the effect of these treatments on lipid parameters and safety events.

Results: The results revealed that combination therapy was more effective in reducing low-density lipoprotein cholesterol (LDL-C) levels (SMD= - 0.41; CI - 0.63 to - 0.19; P = 0.0002). There was no significant change in the levels of high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC), triglyceride (TG), high-sensitivity C-reactive protein (hs-CRP), Apo A1, or Apo B. The safety of these treatments was assessed by the following markers alanine aminotransferase (ALT), aspartate aminotransferase (AST), and creatine phosphokinase (CK), and a significant difference was only observed in CK (SMD: - 0.81; CI - 1.52 to - 0.10; P = 0.02).

Conclusion: This meta-analysis demonstrated that the use of low/moderate-intensity statin combination therapy significantly reduced LDL-C levels compared with high-intensity statin monotherapy, making it preferable for patients with related risks. However, further trials are encouraged to evaluate potential adverse effects associated with combined therapy.

Publication types

  • Meta-Analysis

MeSH terms

  • Anticholesteremic Agents* / administration & dosage
  • Anticholesteremic Agents* / adverse effects
  • Anticholesteremic Agents* / therapeutic use
  • Atherosclerosis* / drug therapy
  • Cardiovascular Diseases
  • Cholesterol, HDL / blood
  • Cholesterol, LDL / blood
  • Drug Therapy, Combination*
  • Ezetimibe* / administration & dosage
  • Ezetimibe* / adverse effects
  • Ezetimibe* / therapeutic use
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors* / administration & dosage
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors* / adverse effects
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors* / therapeutic use
  • Hypercholesterolemia / drug therapy
  • Randomized Controlled Trials as Topic

Substances

  • Anticholesteremic Agents
  • Cholesterol, HDL
  • Cholesterol, LDL
  • Ezetimibe
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors