心血管疾病或心血管危险因素合并糖耐量受损人群的国际结局差异：来自 NAVIGATOR 试验的见解

International Variation in Outcomes Among People with Cardiovascular Disease or Cardiovascular Risk Factors and Impaired Glucose Tolerance: Insights from the NAVIGATOR Trial.

作者信息

Harumi Higuchi Dos Santos Marilia, Sharma Abhinav, Sun Jie-Lena, Pieper Karen, McMurray John J V, Holman Rury R, Lopes Renato D

机构信息

Instituto do Coração do Hospital das Clínicas, FMUSP, São Paulo, Brazil.

Duke Clinical Research Institute, Duke University, Durham, NC.

出版信息

J Am Heart Assoc. 2017 Jan 13;6(1):e003892. doi: 10.1161/JAHA.116.003892.

DOI:10.1161/JAHA.116.003892

PMID:28087508

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5523624/

Abstract

BACKGROUND

Regional differences in risk of diabetes mellitus and cardiovascular outcomes in people with impaired glucose tolerance are poorly characterized. Our objective was to evaluate regional variation in risk of new-onset diabetes mellitus, cardiovascular outcomes, and treatment effects in participants from the NAVIGATOR (Nateglinide and Valsartan in Impaired Glucose Tolerance Outcomes Research) trial.

METHODS AND RESULTS

NAVIGATOR randomized people with impaired glucose tolerance and cardiovascular risk factors or with established cardiovascular disease to valsartan (or placebo) and to nateglinide (or placebo) with a median 5-year follow-up. Data from the 9306 participants were categorized by 5 regions: Asia (n=552); Europe (n=4909); Latin America (n=1406); North America (n=2146); and Australia, New Zealand, and South Africa (n=293). Analyzed outcomes included new-onset diabetes mellitus; cardiovascular death; a composite cardiovascular outcome of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke; and treatment effects of valsartan and nateglinide. Respective unadjusted 5-year risks for new-onset diabetes mellitus, cardiovascular death, and the composite cardiovascular outcome were 33%, 0.4%, and 4% for Asia; 34%, 2%, and 6% for Europe; 37%, 4%, and 8% for Latin America; 38%, 2%, and 6% for North America; and 32%, 4%, and 8% for Australia, New Zealand, and South Africa. After adjustment, compared with North America, European participants had a lower risk of new-onset diabetes mellitus (hazard ratio 0.86, 95% CI 0.78-0.94; P=0.001), whereas Latin American participants had a higher risk of cardiovascular death (hazard ratio 2.68, 95% CI 1.82-3.96; P<0.0001) and the composite cardiovascular outcome (hazard ratio 1.48, 95% CI 1.15-1.92; P=0.003). No differential interactions between treatment and geographic location were identified.

CONCLUSIONS

Major regional differences regarding the risk of new-onset diabetes mellitus and cardiovascular outcomes in NAVIGATOR participants were identified. These differences should be taken into account when planning global trials.

CLINICAL TRIAL REGISTRATION

URL: http://www.ClinicalTrials.gov. Unique identifier: NCT00097786.

摘要

背景

糖耐量受损人群中糖尿病风险和心血管结局的区域差异尚未得到充分描述。我们的目的是评估NAVIGATOR（那格列奈和缬沙坦在糖耐量受损结局研究）试验参与者中新发糖尿病风险、心血管结局及治疗效果的区域差异。

方法与结果

NAVIGATOR将糖耐量受损且有心血管危险因素或已确诊心血管疾病的患者随机分为缬沙坦（或安慰剂）组和那格列奈（或安慰剂）组，中位随访时间为5年。来自9306名参与者的数据按5个区域分类：亚洲（n = 552）；欧洲（n = 4909）；拉丁美洲（n = 1406）；北美洲（n = 2146）；以及澳大利亚、新西兰和南非（n = 293）。分析的结局包括新发糖尿病；心血管死亡；心血管死亡、非致死性心肌梗死或非致死性卒中的复合心血管结局；以及缬沙坦和那格列奈的治疗效果。亚洲新发糖尿病、心血管死亡及复合心血管结局的未调整5年风险分别为33%、0.4%和4%；欧洲分别为34%、2%和6%；拉丁美洲分别为37%、4%和8%；北美洲分别为38%、2%和6%；澳大利亚、新西兰和南非分别为32%、4%和8%。调整后，与北美洲相比，欧洲参与者新发糖尿病风险较低（风险比0.86，95%可信区间0.78 - 0.94；P = 0.001），而拉丁美洲参与者心血管死亡风险较高（风险比2.68，95%可信区间1.82 - 3.96；P < 0.0001）以及复合心血管结局风险较高（风险比1.48，95%可信区间1.15 - 1.92；P = 0.003）。未发现治疗与地理位置之间存在差异相互作用。