Treat-to-Target or High-Intensity Statin in Patients With Coronary Artery Disease
Authors: Hong Sung-Jin , Lee Yong-Joon , Lee Seung-Jun , Hong Bum-Kee , Kang Woong Chol , Lee Jong-Young , Lee Jin-Bae , Yang Tae-Hyun , Yoon Junghan , Ahn Chul-Min , Kim Jung-Sun , Kim Byeong-Keuk , Ko Young-Guk , Choi Donghoon , Jang Yangsoo , Hong Myeong-Ki ,   LODESTAR Investigators, Hong Myeong-Ki , Choi Donghoon , Ko Young-Guk , Kim Byeong-Keuk , Kim Jung-Sun , Ahn Chul-Min , Hong Sung-Jin , Lee Seung-Jun , Lee Yong-Joon , Hong Bum-Kee , Kwon Hyuck Moon , Kim Jong-Youn , Min Pil Ki , Yoon Young Won , Lee Byoung Kwon , Rim Se-Joong , Choi Eui-Young , Kang Woong Chol , Oh Pyung Chun , Lee Jong-Young , Lee Jin-Bae , Kim Kee Sik , Choi Ji Yong , Ryu Jae Kean , Hong Seung Pyo , Kim Chang Yeon , Yang Tae-Hyun , Cho Hyung-Jin , Yoon Junghan , Ahn Min-Soo , Ahn Sung Gyun , Lee Jun-Won , Son Jung-Woo , Jang Yangsoo , Yoon Hyuck-Jun , Lee Cheol Hyun , Hwang Jongmin , Cho Yun-Kyeong , Hur Seung-Ho , Han Seongwook , Nam Chang-Wook , Kim Hyoungseop , Park Hyoung-Seob , Kim In-Cheol , Cho Yun-Hyeong , Jeong Hyeon-Ju , Kim Jin-Ho , Lim Chewan , Suh Yongsung , Hwang Eui Seok , Lee Ji Hyun , Lee Sung Yun , Kwon Sung Uk , Kim Song-Yi , Park Keun-Ho , Kim Hyun Kuk 
Published: March 2023

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 &amp;lt; .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