Korean Circ J.  2024 Sep;54(9):534-544. 10.4070/kcj.2024.0036.

Comparison of Statin With Ezetimibe Combination Therapy Versus Statin Monotherapy for Primary Prevention in Middle-Aged Adults

• Cha JJ
• Hong SJ
• Lim S
• Kim JH
• Joo HJ
• Park JH
• Yu CW
• Lim DS
• Kim JY
• Jeong JO
• Shin JH
• Shim CY
• Lee JY
• Lim YH
• Park SH
• Cho EJ
• Kim H
• Lee J
• Sung KC
• on behalf of the Korean Vascular Society

• KMID: 2559125
• DOI: http://doi.org/10.4070/kcj.2024.0036

Abstract

Background and Objectives
Lipid lowering therapy is essential to reduce the risk of major cardiovascular events; however, limited evidence exists regarding the use of statin with ezetimibe as primary prevention strategy for middle-aged adults. We aimed to investigate the impact of single pill combination therapy on clinical outcomes in relatively healthy middleaged patients when compared with statin monotherapy.
Methods
Using the Korean National Health Insurance Service database, a propensity score match analysis was performed for baseline characteristics of 92,156 patients categorized into combination therapy (n=46,078) and statin monotherapy (n=46,078) groups. Primary outcome was composite outcomes, including death, coronary artery disease, and ischemic stroke. And secondary outcome was all-cause death. The mean follow-up duration was 2.9±0.3 years.
Results
The 3-year composite outcomes of all-cause death, coronary artery disease, and ischemic stroke demonstrated no significant difference between the 2 groups (10.3% vs. 10.1%; hazard ratio [HR], 1.022; 95% confidence interval [CI], 0.980–1.064; p=0.309). Meanwhile, the 3-year all-cause death rate was lower in the combination therapy group than in the statin monotherapy group (0.2% vs. 0.4%; p<0.001), with a significant HR of 0.595 (95% CI, 0.460–0.769; p<0.001). Single pill combination therapy exhibited consistently lower mortality rates across various subgroups.
Conclusions
Compared to the statin monotherapy, the combination therapy for primary prevention showed no difference in composite outcomes but may reduce mortality risk in relatively healthy middle-aged patients. However, since the study was observational, further randomized clinical trials are needed to confirm these findings.

Keyword

Primary prevention; Ezetimibe; Hydroxymethylglutaryl-CoA reductase inhibitors

Figure

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  Figure 1 Flow chart of recruitment of the study participants.NHIS = National Health Insurance Service.

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  Figure 2 Comparison of the cumulative incidence between statin monotherapy and combination therapy groups. (A) Composite endpoint, (B) all-cause death, (C) coronary artery disease, and (D) ischemic stroke.

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  Figure 3 Exploratory subgroup analysis in 3-year all-cause death according to the lipid-lowering therapy strategy.CI = confidence interval; HDL-C = high-density lipoprotein cholesterol; HR = hazard ratio; LDL-C = low-density lipoprotein cholesterol; TG = triglyceride.

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