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

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.

Figure 1.. Recruitment, Randomization, and Follow-up in a Trial of Treat-to-Target Strategy or High-Intensity Statin Therapy for Coronary Artery Disease

^aData regarding screening were not collected. ^bRandomization was stratified by baseline low-density lipoprotein cholesterol levels of 100 mg/dL or greater, acute coronary syndrome, and the presence of diabetes.

Figure 2.. Lipid-Lowering Therapy During the Study Period

Figure 3.. Changes in LDL-C Levels and Kaplan-Meier Curves for the Primary End Point^a

In panel A, the middle lines in the box plots represent the median values, boxes represent the IQRs, whiskers extend to the most extreme observed values with 1.5 × the IQR of the nearer quartile, and dots represent observed values outside that range. Reference values may vary based on laboratory and location. LDL-C indicates low-density lipoprotein cholesterol; MI, myocardial infarction. ^aChanges in total cholesterol, triglyceride, and high-density lipoprotein cholesterol levels over time are also presented in eFigure 1 in Supplement 2.