University of Exeter Medical School, St Luke's Campus, United Kingdom (W.D.S., M.A.J.).
Academic Department of Healthcare for Older People, Royal Devon and Exeter NHS Foundation Trust, United Kingdom (W.D.S., M.A.J.).
Stroke. 2022 Sep;53(9):2749-2757. doi: 10.1161/STROKEAHA.121.037775. Epub 2022 May 18.
GLP-1 RA (glucagon-like peptide-1 receptor agonists), including semaglutide, may reduce stroke risk in people with type 2 diabetes. This post hoc analysis examined the subcutaneous and oral semaglutide effects, versus placebo, on stroke and its subtypes in people with type 2 diabetes at high cardiovascular risk.
SUSTAIN 6 (Trial to Evaluate Cardiovascular and Other Long-Term Outcomes With Semaglutide in Subjects With Type 2 Diabetes) and PIONEER 6 (Peptide Innovation for Early Diabetes Treatment) were randomized cardiovascular outcome trials of subcutaneous and oral semaglutide in people with type 2 diabetes at high cardiovascular risk, respectively. Time to first stroke and stroke subtypes were analyzed using a Cox proportional hazards model stratified by trial with pooled treatment as a factor. The impact of prior stroke, prior myocardial infarction or stroke, age, sex, systolic blood pressure, estimated glomerular filtration rate, and prior atrial fibrillation on treatment effects was assessed using interaction values. Risk of major adverse cardiovascular event was analyzed according to prior stroke.
A total of 106/6480 participants had a stroke (1.0 event/100 patient-years of observation [PYO]). Semaglutide reduced incidence of any stroke versus placebo (0.8 versus 1.1 events/100 PYO; hazard ratio, 0.68 [95% CI, 0.46-1.00]; =0.048), driven by significant reductions in risk of small-vessel occlusion (0.3 versus 0.7 events/100 PYO; hazard ratio, 0.51 [95% CI, 0.29-0.89]; =0.017). Hazard ratios for risk of any stroke with semaglutide versus placebo were 0.60 (95% CI, 0.37-0.99; 0.5 versus 0.9 events/100 PYO) and 0.89 (95% CI, 0.47-1.69; 2.7 versus 3.0 events/100 PYO) in those without and with prior stroke, respectively. Except for prior atrial fibrillation (=0.025), no significant interactions were observed between treatment effects on risk of any stroke and subgroups investigated, or between treatment effects on risk of major adverse cardiovascular event and prior stroke ( >0.05 for all).
Semaglutide reduced incidence of any first stroke during the trials versus placebo in people with type 2 diabetes at high cardiovascular risk, primarily driven by small-vessel occlusion prevention. Semaglutide treatment, versus placebo, lowered the risk of stroke irrespective of prior stroke at baseline.
URL: https://www.
gov; Unique identifier: NCT01720446 and NCT02692716.
GLP-1RA（胰高血糖素样肽-1 受体激动剂），包括司美格鲁肽，可能降低 2 型糖尿病患者的中风风险。本事后分析检查了皮下和口服司美格鲁肽与安慰剂相比，对 2 型糖尿病高心血管风险患者中风及其亚型的影响。
SUSTAIN 6（在 2 型糖尿病患者中评估司美格鲁肽的心血管和其他长期结局的试验）和 PIONEER 6（用于早期糖尿病治疗的肽创新）分别是皮下和口服司美格鲁肽在高心血管风险 2 型糖尿病患者中的随机心血管结局试验。采用 Cox 比例风险模型，按试验分层，以联合治疗为因素，分析首次中风和中风亚型的时间。使用交互值评估既往中风、既往心肌梗死或中风、年龄、性别、收缩压、估计肾小球滤过率和既往心房颤动对治疗效果的影响。根据既往中风分析主要不良心血管事件的风险。
共有 106/6480 名参与者发生中风（1.0 例/100 名患者年观察[PYO]）。与安慰剂相比，司美格鲁肽降低了任何中风的发生率（0.8 例/100 PYO 与 1.1 例/100 PYO；风险比，0.68[95%CI，0.46-1.00]；=0.048），这主要归因于小血管闭塞风险的显著降低（0.3 例/100 PYO 与 0.7 例/100 PYO；风险比，0.51[95%CI，0.29-0.89]；=0.017）。与安慰剂相比，司美格鲁肽降低任何中风风险的风险比分别为 0.60（95%CI，0.37-0.99；0.5 例/100 PYO 与 0.9 例/100 PYO）和 0.89（95%CI，0.47-1.69；2.7 例/100 PYO 与 3.0 例/100 PYO），分别为既往无中风和既往有中风的患者。除了既往心房颤动（=0.025）外，在治疗效果与所研究的亚组之间，或在治疗效果与主要不良心血管事件风险与既往中风之间（所有=0.05）均未观察到显著的交互作用。
与安慰剂相比，司美格鲁肽降低了高心血管风险 2 型糖尿病患者在试验期间任何首次中风的发生率，主要归因于小血管闭塞的预防。与安慰剂相比，司美格鲁肽治疗降低了中风风险，无论基线时是否有既往中风。
NCT01720446 和 NCT02692716。
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