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Original Investigation
March 6, 2023

Treat-to-Target or High-Intensity Statin in Patients With Coronary Artery Disease: A Randomized Clinical Trial

Author Affiliations
  • 1Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea
  • 2Gangnam Severance Hospital, Seoul, South Korea
  • 3Gachon University College of Medicine, Incheon, South Korea
  • 4Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, South Korea
  • 5Daegu Catholic University Medical Center, Daegu, South Korea
  • 6Inje University Busan Paik Hospital, Busan, South Korea
  • 7Wonju Severance Christian Hospital, Wonju, South Korea
  • 8CHA University College of Medicine, Seongnam, South Korea
JAMA. Published online March 6, 2023. doi:10.1001/jama.2023.2487
Visual Abstract. Treat-to-Target or High-Intensity Statin in Patients With Coronary Artery Disease
Treat-to-Target or High-Intensity Statin in Patients With Coronary Artery Disease
Key Points

Question  Is treatment to a goal low-density lipoprotein cholesterol (LDL-C) level between 50 and 70 mg/dL noninferior to a strategy using high-intensity statin therapy among patients with coronary artery disease?

Findings  In this randomized noninferiority trial that included 4400 patients with coronary artery disease, the rate of the 3-year composite of all-cause death, myocardial infarction, stroke, or any coronary revascularization was 8.1% in the treat-to-target strategy group compared with 8.7% in the high-intensity statin therapy group, a difference that met the prespecified noninferiority margin of 3.0 percentage points.

Meaning  Among patients with coronary artery disease, the treat-to-target LDL-C strategy was noninferior to the high-intensity statin strategy for major clinical outcomes.

Abstract

Importance  In patients with coronary artery disease, some guidelines recommend initial statin treatment with high-intensity statins to achieve at least a 50% reduction in low-density lipoprotein cholesterol (LDL-C). An alternative approach is to begin with moderate-intensity statins and titrate to a specific LDL-C goal. These alternatives have not been compared head-to-head in a clinical trial involving patients with known coronary artery disease.

Objective  To assess whether a treat-to-target strategy is noninferior to a strategy of high-intensity statins for long-term clinical outcomes in patients with coronary artery disease.

Design, Setting, and Participants  A randomized, multicenter, noninferiority trial in patients with a coronary disease diagnosis treated at 12 centers in South Korea (enrollment: September 9, 2016, through November 27, 2019; final follow-up: October 26, 2022).

Interventions  Patients were randomly assigned to receive either the LDL-C target strategy, with an LDL-C level between 50 and 70 mg/dL as the target, or high-intensity statin treatment, which consisted of rosuvastatin, 20 mg, or atorvastatin, 40 mg.

Main Outcomes and Measures  Primary end point was a 3-year composite of death, myocardial infarction, stroke, or coronary revascularization with a noninferiority margin of 3.0 percentage points.

Results  Among 4400 patients, 4341 patients (98.7%) completed the trial (mean [SD] age, 65.1 [9.9] years; 1228 females [27.9%]). In the treat-to-target group (n = 2200), which had 6449 person-years of follow-up, moderate-intensity and high-intensity dosing were used in 43% and 54%, respectively. The mean (SD) LDL-C level for 3 years was 69.1 (17.8) mg/dL in the treat-to-target group and 68.4 (20.1) mg/dL in the high-intensity statin group (n = 2200) (P = .21, compared with the treat-to-target group). The primary end point occurred in 177 patients (8.1%) in the treat-to-target group and 190 patients (8.7%) in the high-intensity statin group (absolute difference, –0.6 percentage points [upper boundary of the 1-sided 97.5% CI, 1.1 percentage points]; P < .001 for noninferiority).

Conclusions and Relevance  Among patients with coronary artery disease, a treat-to-target LDL-C strategy of 50 to 70 mg/dL as the goal was noninferior to a high-intensity statin therapy for the 3-year composite of death, myocardial infarction, stroke, or coronary revascularization. These findings provide additional evidence supporting the suitability of a treat-to-target strategy that may allow a tailored approach with consideration for individual variability in drug response to statin therapy.

Trial Registration  ClinicalTrials.gov Identifier: NCT02579499

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