INSERM LVTS-U1148, DHU FIRE, Department of Neurology and Stroke Center, Bichat Hospital, Assistance Publique-Hôpitaux de Paris (APHP), University of Paris, Paris, France
Asan Medical Center, Seoul, South Korea.
Diabetes. 2021 Aug;70(8):1807-1815. doi: 10.2337/db21-0302. Epub 2021 May 12.
After an ischemic stroke with evidence of atherosclerosis, lipid-lowering treatment with a target LDL cholesterol of <70 mg/dL compared with 100 ± 10 mg/dL reduced the risk of subsequent cardiovascular events. In this analysis, we explored the effect in the subgroup of patients with diabetes compared with the subgroup without, as well as in those with newly diagnosed diabetes. Patients with ischemic stroke in the previous 3 months or transient ischemic attack within the previous 15 days and evidence of cerebrovascular or coronary artery atherosclerosis were randomly assigned at a 1:1 ratio to a target LDL cholesterol of <70 mg/dL or 100 ± 10 mg/dL using statin or ezetimibe. The primary outcome was the composite of ischemic stroke, myocardial infarction, new symptoms requiring urgent coronary or carotid revascularization, and death resulting from vascular disease. We performed a prespecified analysis to evaluate the effect in patients with diabetes. Of 2,860 patients enrolled, 643 had diabetes at baseline, with a mean age of 66.2 years and baseline LDL cholesterol of 127 mg/dL, and were followed for a median of 3 years. The primary composite end point occurred in 27 (8.2%) of 328 patients in the lower-target group and in 44 (14.0%) of 315 patients in the higher-target group (adjusted hazard ratio [HR] 0.56; 95% CI 0.34-0.89; = 0.016). In patients without diabetes, the HR was 0.87 (95% CI 0.66-1.14; = 0.31; interaction = 0.15). In those with diabetes, there were three intracranial hemorrhages in both randomization groups (0.9% vs. 1.0%, respectively). Newly diagnosed diabetes occurred in 98 (9.2%) of 1,070 and in 80 (7.4%) of 1,085 patients in the lower- and higher-target groups, respectively (HR 1.27; 95% CI 0.94-1.71; = 0.11), and baseline higher HbA was the unique multivariable predictor. In conclusion, after an ischemic stroke with evidence of atherosclerosis, targeting an LDL cholesterol of <70 mg/dL compared with 100 ± 10 mg/dL consistently reduced the risk of subsequent stroke and other major vascular events in patients with and without diabetes, but the higher risk in those with diabetes yielded a higher absolute risk reduction, with number needed to treat of 17.
在有动脉粥样硬化证据的缺血性卒中后，与目标 LDL 胆固醇 100±10mg/dL 相比，将 LDL 胆固醇降至<70mg/dL 可降低随后发生心血管事件的风险。在此分析中，我们探索了在糖尿病亚组与非糖尿病亚组以及新发糖尿病患者中的作用。在过去 3 个月内发生缺血性卒中或过去 15 天内发生短暂性脑缺血发作且有脑血管或冠状动脉粥样硬化证据的患者，按 1:1 的比例随机分配至 LDL 胆固醇<70mg/dL 或 100±10mg/dL 组，采用他汀类药物或依折麦布进行治疗。主要复合终点为缺血性卒中、心肌梗死、新出现的需要紧急冠状动脉或颈动脉血运重建的症状和血管疾病导致的死亡。我们进行了预设分析以评估糖尿病患者的作用。在纳入的 2860 例患者中，643 例患者在基线时有糖尿病，平均年龄为 66.2 岁，基线 LDL 胆固醇为 127mg/dL，中位随访时间为 3 年。在较低目标组的 328 例患者中有 27 例（8.2%）和在较高目标组的 315 例患者中有 44 例（14.0%）发生主要复合终点（校正后的 HR 0.56；95%CI 0.34-0.89； = 0.016）。在无糖尿病患者中，HR 为 0.87（95%CI 0.66-1.14； = 0.31；交互作用=0.15）。在有糖尿病的患者中，两组各有 3 例颅内出血（分别为 0.9%和 1.0%）。新发糖尿病患者在较低目标组的 1070 例患者中有 98 例（9.2%）和在较高目标组的 1085 例患者中有 80 例（7.4%）（HR 1.27；95%CI 0.94-1.71； = 0.11），且基线较高的糖化血红蛋白是唯一的多变量预测因素。总之，在有动脉粥样硬化证据的缺血性卒中后，与 LDL 胆固醇 100±10mg/dL 相比，将 LDL 胆固醇目标值降至<70mg/dL 可一致降低有或无糖尿病患者随后发生卒中及其他主要血管事件的风险，但糖尿病患者的风险较高，导致绝对风险降低幅度更大，治疗需治疗人数为 17。
