Cavender Matthew A, Scirica Benjamin M, Raz Itamar, Steg Ph Gabriel, McGuire Darren K, Leiter Lawrence A, Hirshberg Boaz, Davidson Jaime, Cahn Avivit, Mosenzon Ofri, Im KyungAh, Braunwald Eugene, Bhatt Deepak L
Thrombolysis in Myocardial Infarction (TIMI) Study Group, Heart and Vascular Center, Brigham and Women's Hospital, and Harvard Medical School, Boston, Mass.
Diabetes Unit, Department of Internal Medicine, Hadassah Hebrew University Hospital, Jerusalem, Israel.
Am J Med. 2016 Mar;129(3):340.e1-8. doi: 10.1016/j.amjmed.2015.09.022. Epub 2015 Oct 31.
The effect of saxagliptin on cardiovascular outcomes according to different hemoglobin A1c (HbA1c) levels has not been described. Thus, we analyzed the SAVOR-TIMI 53 trial to compare the cardiovascular effects of saxagliptin vs placebo according to baseline HbA1c.
A total of 16,492 patients with type 2 diabetes (HbA1c 6.5%-12.0% in the 6 months before randomization) and either a history of established cardiovascular disease or multiple risk factors for atherosclerosis were randomized to saxagliptin or placebo in addition to usual care. Patients were followed for a median of 2.1 years. The primary endpoint was cardiovascular death, myocardial infarction, or ischemic stroke.
Patients were stratified by HbA1c at randomization into the following prespecified groups: <7%, 7%-<8%, 8%-<9%, and ≥9%. Baseline HbA1c ≥7% was associated with increased risk of cardiovascular death, myocardial infarction, or ischemic stroke (adjusted hazard ratio [HR(adj)] 1.35; 95% confidence interval [CI], 1.17-1.58) but not hospitalization for heart failure (HR(adj) 1.09; 95% CI, 0.88-1.36). Saxagliptin neither increased nor decreased the risk of cardiovascular death, myocardial infarction, or ischemic stroke in patients with HbA1c <7% (HR 1.01; 95% CI, 0.78-1.31), 7%-<8% (HR 0.98; 95% CI, 0.80-1.20), 8%-<9% (HR 1.09; 95% CI, 0.85-1.39), ≥9% (HR 0.95; 95% CI, 0.77-1.18) (P-interaction = .89).
Baseline HbA1c is associated with increased risk of macrovascular events but not hospitalization for heart failure. There was no heterogeneity in the effect of saxagliptin on cardiovascular events by baseline HbA1c, with cardiovascular death, myocardial infarction, or ischemic stroke neither increased nor decreased across the spectrum of baseline HbA1c values.
尚未描述沙格列汀对不同糖化血红蛋白（HbA1c）水平患者心血管结局的影响。因此，我们分析了SAVOR-TIMI 53试验，以比较沙格列汀与安慰剂根据基线HbA1c水平对心血管的影响。
共有16492例2型糖尿病患者（随机分组前6个月HbA1c为6.5%-12.0%），且有已确诊的心血管疾病史或多个动脉粥样硬化危险因素，除常规治疗外，被随机分为沙格列汀组或安慰剂组。对患者进行了中位时间为2.1年的随访。主要终点为心血管死亡、心肌梗死或缺血性卒中。
根据随机分组时的HbA1c水平将患者分层为以下预先设定的组：<7%、7%-<8%、8%-<9%和≥9%。基线HbA1c≥7%与心血管死亡、心肌梗死或缺血性卒中风险增加相关（校正风险比[HR(adj)]为1.35；95%置信区间[CI]，1.17-1.58），但与因心力衰竭住院无关（HR(adj)为1.09；95%CI，0.88-1.36）。沙格列汀对HbA1c<7%（HR为1.01；95%CI，0.78-1.31）、7%-<8%（HR为0.98；95%CI，0.80-1.20）、8%-<9%（HR为1.09；95%CI，0.85-1.39）、≥9%（HR为0.95；95%CI，0.77-1.18）的患者，既未增加也未降低心血管死亡、心肌梗死或缺血性卒中的风险（P交互作用=0.89）。
基线HbA1c与大血管事件风险增加相关，但与因心力衰竭住院无关。沙格列汀对心血管事件的影响在不同基线HbA1c水平之间不存在异质性，在整个基线HbA1c值范围内，心血管死亡、心肌梗死或缺血性卒中的风险既未增加也未降低。
