射血分数降低的心力衰竭患者中与糖尿病前期和糖尿病相关的风险：血管紧张素受体脑啡肽酶抑制剂与血管紧张素转换酶抑制剂前瞻性比较以确定对心力衰竭试验全球死亡率和发病率影响的见解。
Risk Related to Pre-Diabetes Mellitus and Diabetes Mellitus in Heart Failure With Reduced Ejection Fraction: Insights From Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure Trial.
作者信息
Kristensen Søren L, Preiss David, Jhund Pardeep S, Squire Iain, Cardoso José Silva, Merkely Bela, Martinez Felipe, Starling Randall C, Desai Akshay S, Lefkowitz Martin P, Rizkala Adel R, Rouleau Jean L, Shi Victor C, Solomon Scott D, Swedberg Karl, Zile Michael R, McMurray John J V, Packer Milton
机构信息
From the British Heart Foundation, Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom (S.L.K., D.P., P.J., J.J.V.M.); Department of Cardiology, Gentofte University Hospital, Copenhagen, Denmark (S.L.K.); Department of Cardiovascular Sciences, University of Leicester, Leicester, UK (I.S.); NIHR Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester, UK (I.S.); Department of Cardiology, Porto Medical School, Porto, Portugal (J.S.C.); Heart and Vascular Center Semmelweiss University, Budapest, Hungary (B.M.); Instituo DAMIC, Cordoba National University, Cordoba, Argentina (F.M.); Kaufman Center for Heart Failure, Heart and Vascular Institute, Cleveland Clinic, OH (R.C.S.); Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA (A.S.D); Novartis Pharmaceutical Corporation, East Hanover, NJ (M.P.L., A.R.R., V.C.S.); Institut de Cardiologie, Université de Montréal, Montréal, Québec, Canada (J.L.R.); Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden (K.S.); RHJ Department of Veterans Administration Medical Center, Medical University of South Carolina, Charleston (M.R.Z.); and Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas (M.P.).
出版信息
Circ Heart Fail. 2016 Jan;9(1). doi: 10.1161/CIRCHEARTFAILURE.115.002560.
BACKGROUND
The prevalence of pre-diabetes mellitus and its consequences in patients with heart failure and reduced ejection fraction are not known. We investigated these in the Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM-HF) trial.
METHODS AND RESULTS
We examined clinical outcomes in 8399 patients with heart failure and reduced ejection fraction according to history of diabetes mellitus and glycemic status (baseline hemoglobin A1c [HbA1c]: < 6.0% [< 42 mmol/mol], 6.0%-6.4% [42-47 mmol/mol; pre-diabetes mellitus], and ≥ 6.5% [≥ 48 mmol/mol; diabetes mellitus]), in Cox regression models adjusted for known predictors of poor outcome. Patients with a history of diabetes mellitus (n = 2907 [35%]) had a higher risk of the primary composite outcome of heart failure hospitalization or cardiovascular mortality compared with those without a history of diabetes mellitus: adjusted hazard ratio, 1.38; 95% confidence interval, 1.25 to 1.52; P < 0.001. HbA1c measurement showed that an additional 1106 (13% of total) patients had undiagnosed diabetes mellitus and 2103 (25%) had pre-diabetes mellitus. The hazard ratio for patients with undiagnosed diabetes mellitus (HbA1c, > 6.5%) and known diabetes mellitus compared with those with HbA1c < 6.0% was 1.39 (1.17-1.64); P < 0.001 and 1.64 (1.43-1.87); P < 0.001, respectively. Patients with pre-diabetes mellitus were also at higher risk (hazard ratio, 1.27 [1.10-1.47]; P < 0.001) compared with those with HbA1c < 6.0%. The benefit of LCZ696 (sacubitril/valsartan) compared with enalapril was consistent across the range of HbA1c in the trial.
CONCLUSIONS
In patients with heart failure and reduced ejection fraction, dysglycemia is common and pre-diabetes mellitus is associated with a higher risk of adverse cardiovascular outcomes (compared with patients with no diabetes mellitus and HbA1c < 6.0%). LCZ696 was beneficial compared with enalapril, irrespective of glycemic status.
CLINICAL TRIAL REGISTRATION
URL: http://www.clinicaltrials.gov. Unique identifier: NCT01035255.
背景
射血分数降低的心力衰竭患者中糖尿病前期的患病率及其后果尚不清楚。我们在ARNI与ACEI对心力衰竭全球死亡率和发病率影响的前瞻性比较（PARADIGM-HF）试验中对此进行了研究。
方法和结果
我们根据糖尿病病史和血糖状态（基线糖化血红蛋白[HbA1c]：<6.0% [<42 mmol/mol]、6.0%-6.4% [42-47 mmol/mol；糖尿病前期]和≥6.5% [≥48 mmol/mol；糖尿病]），在针对已知不良预后预测因素进行调整的Cox回归模型中，对8399例射血分数降低的心力衰竭患者的临床结局进行了检查。有糖尿病病史的患者（n = 2907 [35%]）与无糖尿病病史的患者相比，发生心力衰竭住院或心血管死亡的主要复合结局的风险更高：调整后的风险比为1.38；95%置信区间为1.25至1.52；P<0.001。HbA1c测量显示，另有1106例（占总数的13%）患者患有未确诊的糖尿病，2103例（25%）患有糖尿病前期。未确诊糖尿病（HbA1c>6.5%）和已知糖尿病患者与HbA1c<6.0%的患者相比，风险比分别为1.39（1.17-1.64）；P<0.001和1.64（1.43-1.87）；P<0.001。与HbA1c<6.0%的患者相比，糖尿病前期患者的风险也更高（风险比为1.27 [1.10-1.47]；P<0.001）。在试验中，与依那普利相比，LCZ696（沙库巴曲/缬沙坦）的益处贯穿HbA1c的整个范围。
结论
在射血分数降低的心力衰竭患者中，血糖异常很常见，糖尿病前期与不良心血管结局的较高风险相关（与无糖尿病且HbA1c<6.0%的患者相比）。与依那普利相比，无论血糖状态如何，LCZ696均有益处。
临床试验注册
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