Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea.
Gangnam Severance Hospital, Seoul, South Korea.
JAMA. 2023 Apr 4;329(13):1078-1087. doi: 10.1001/jama.2023.2487.
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.
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).
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.
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.
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).
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.
ClinicalTrials.gov Identifier: NCT02579499.
在患有冠状动脉疾病的患者中，一些指南建议初始使用高强度他汀类药物进行他汀类药物治疗，以实现低密度脂蛋白胆固醇（LDL-C）降低至少 50%。另一种方法是开始使用中等强度的他汀类药物，并滴定至特定的 LDL-C 目标。这些替代方法尚未在涉及已知冠状动脉疾病的患者的临床试验中进行头对头比较。
评估针对目标的治疗策略是否不如高强度他汀类药物治疗策略对冠状动脉疾病患者的长期临床结局更有效。
设计、地点和参与者：这是一项在韩国 12 个中心进行的随机、多中心、非劣效性试验（入组时间：2016 年 9 月 9 日至 2019 年 11 月 27 日；最终随访时间：2022 年 10 月 26 日）。
患者被随机分配接受 LDL-C 目标策略或高强度他汀类药物治疗。LDL-C 目标策略的目标 LDL-C 水平为 50-70mg/dL，高强度他汀类药物治疗包括瑞舒伐他汀 20mg 或阿托伐他汀 40mg。
主要终点是 3 年内死亡、心肌梗死、卒中和冠状动脉血运重建的复合终点，非劣效性边界为 3.0 个百分点。
在 4400 名患者中，4341 名患者（98.7%）完成了试验（平均[SD]年龄 65.1[9.9]岁；1228 名女性[27.9%]）。在针对目标的治疗组（n=2200）中，随访 6449 人年，分别有 43%和 54%的患者接受了中等强度和高强度剂量。针对目标治疗组 3 年内的平均（SD）LDL-C 水平为 69.1（17.8）mg/dL，高强度他汀类药物治疗组为 68.4（20.1）mg/dL（n=2200）（P=.21，与针对目标治疗组相比）。针对目标治疗组有 177 名患者（8.1%）和高强度他汀类药物治疗组有 190 名患者（8.7%）发生主要终点事件（绝对差值为-0.6 个百分点[单侧 97.5%CI 的上限为 1.1 个百分点]；P<.001 表示非劣效性）。
在患有冠状动脉疾病的患者中，以 50-70mg/dL 为目标的 LDL-C 目标治疗策略与高强度他汀类药物治疗策略相比，在 3 年内的死亡、心肌梗死、卒中和冠状动脉血运重建复合终点方面不劣效。这些发现提供了额外的证据，支持针对目标的治疗策略的适用性，该策略可能允许采用个体化的方法，考虑到他汀类药物治疗的药物反应个体差异。
ClinicalTrials.gov 标识符：NCT02579499。
