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Meta-Analysis
. 2024 Aug;47(8):e24334.
doi: 10.1002/clc.24334.

Safety and Effectiveness of High-Intensity Statins Versus Low/Moderate-Intensity Statins Plus Ezetimibe in Patients With Atherosclerotic Cardiovascular Disease for Reaching LDL-C Goals: A Systematic Review and Meta-Analysis

Hamidreza Soleimani  1   2 , Asma Mousavi  1   2 , Shayan Shojaei  1   2 , Kiarash Tavakoli  1   2 , Dorsa Salabat  1   2 , Farid Farahani Rad  1   2 , Mani K Askari  3 , John Nelson  4 , Mohammed Ruzieh  5 , Kaveh Hosseini  1   2
Affiliations
Meta-Analysis

Safety and Effectiveness of High-Intensity Statins Versus Low/Moderate-Intensity Statins Plus Ezetimibe in Patients With Atherosclerotic Cardiovascular Disease for Reaching LDL-C Goals: A Systematic Review and Meta-Analysis

Hamidreza Soleimani et al. Clin Cardiol. 2024 Aug.

Abstract

Background: It remains controversial whether adding ezetimibe to low/moderate-intensity statins has a more beneficial impact on the treatment efficacy and safety of patients with existing atherosclerotic cardiovascular disease (ASCVD) compared to high-intensity statin regimens.

Hypothesis: A combination of low/moderate-intensity statins plus ezetimibe might be more effective and safer than high-intensity statin monotherapy.

Methods: We searched databases for randomized controlled trials comparing lipid profile alterations, drug-related adverse events, and MACE components between high-intensity statin monotherapy and low/moderate-intensity statin plus ezetimibe combination therapy. Pooled risk ratios (RR), mean differences (MD), and 95% confidence intervals (95% CI) were estimated using a random-effects model.

Results: Our comprehensive search resulted in 32 studies comprising 6162 patients treated with monotherapy against 5880 patients on combination therapy. Combination therapy was more effective in reducing low-density lipoprotein cholesterol (LDL-C) levels compared to monotherapy (MD = -6.6, 95% CI: -10.6 to -2.5); however, no significant differences were observed in other lipid parameters. Furthermore, the combination therapy group experienced a lower risk of myalgia (RR = 0.27, 95% CI: 0.13-0.57) and discontinuation due to adverse events (RR = 0.61, 95% CI: 0.51-0.74). The occurrence of MACE was similar between the two treatment groups.

Conclusions: Adding ezetimibe to low/moderate-intensity statins resulted in a greater reduction in LDL-C levels, a lower rate of myalgia, and less drug discontinuation compared to high-intensity statin monotherapy in patients with existing cardiovascular disease. However, according to our meta-analysis, the observed reduction in LDL-C levels in the combination group did not correlate with a reduction in MACE compared to the high-intensity statin group.

Keywords: atherosclerosis; ezetimibe; meta‐analysis; statin; systematic review.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
PRISMA flow chart.
Figure 2
Figure 2
(A) Mean difference in LDL‐C, (B) mean difference in HDL‐C, (C) mean difference in TG, (D) mean difference in TC, and (E) mean difference in hs‐CRP.
Figure 3
Figure 3
(A) Therapy discontinuation, (B) myalgia, and (C) rise in liver enzymes.
Figure 4
Figure 4
(A) Total MACE, (B) cardiovascular mortality, (C) hospitalization, (D) revascularization, (E) non‐fetal MI, (F) stroke, and (G) all‐cause mortality.
See this image and copyright information in PMC

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