Effect of sacubitril/valsartan versus enalapril on glycaemic control in patients with heart failure and diabetes: a post-hoc analysis from the PARADIGM-HF trial.
Effect of sacubitril/valsartan versus enalapril on glycaemic control in patients with heart failure and diabetes: a post-hoc analysis from the PARADIGM-HF trial.
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DOI：
10.1016/s2213-8587(17)30087-6
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发表时间：
2017-05
期刊：
影响因子：
--
通讯作者：
Solomon SD
中科院分区：
文献类型：
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作者：
Seferovic JP;Claggett B;Seidelmann SB;Seely EW;Packer M;Zile MR;Rouleau JL;Swedberg K;Lefkowitz M;Shi VC;Desai AS;McMurray JJV;Solomon SD
糖尿病是心力衰竭进展的独立危险因素。与血管紧张素转换酶抑制剂依那普利相比，血管紧张素受体-奈普利素联合抑制剂沙比利/缬沙坦可降低射血分数（HFrEF）心力衰竭患者的发病率和死亡率，并可改善肥胖高血压患者的外周胰岛素敏感性。我们的目的是研究苏比里尔/缬沙坦与依那普利对糖尿病和HFrEF患者的HbA1c和首次开始胰岛素或口服降糖药的时间的影响。在范式- hf试验的事后分析中，我们从8399例HFrEF患者中筛选了3778例已知糖尿病或HbA1c≥6.5%的患者，这些患者被随机分配到沙比里尔/缬沙坦或依那普利治疗。在这些患者中，大多数（98%）患有2型糖尿病。我们在混合效应纵向分析模型中评估了HbA1c、甘油三酯、高密度脂蛋白胆固醇和BMI的变化。在治疗组之间比较先前未接受口服降糖药或胰岛素治疗的受试者开始口服降糖药或胰岛素的时间。筛查时，随机分组间HbA1c浓度无显著差异。在随访的第一年，依那普利组的HbA1c浓度下降了0.16% (SD为1.40)，苏比里尔/缬沙坦组的HbA1c浓度下降了0.26% (SD为1.25)（组间下降了0.13%，95% CI为0.05 - 0.22,p= 0.0023）。3年随访期间，沙比利/缬沙坦组HbA1c浓度持续低于依那普利组（组间降低0.14%,95% CI 0.06 - 0.23, p= 0.0055）。与接受依那普利治疗的患者（153例[10%]）相比，接受苏比利/缬沙坦治疗的患者（114例[7%]）新胰岛素使用率低29%；风险比0.71,95% CI 0.56 ~ 0.90, p= 0.0052)。同样，口服降糖治疗的患者较少（0.77,0.58 - 1.02,p= 0.073）， sacubitril/缬沙坦组。在PARADIGM-HF项目中，接受苏比里尔/缬沙坦治疗的糖尿病和HFrEF患者的HbA1c长期降低幅度大于接受依那普利治疗的患者。这些数据表明，sacubitril/缬沙坦可能增强糖尿病和HFrEF患者的血糖控制。
Diabetes is an independent risk factor for heart failure progression. Sacubitril/valsartan, a combination angiotensin receptor-neprilysin inhibitor, improves morbidity and mortality in patients with heart failure with reduced ejection fraction (HFrEF), compared with the angiotensin-converting enzyme inhibitor enalapril, and improves peripheral insulin sensitivity in obese hypertensive patients. We aimed to investigate the effect of sacubitril/valsartan versus enalapril on HbA1c and time to first-time initiation of insulin or oral antihyperglycaemic drugs in patients with diabetes and HFrEF. In a post-hoc analysis of the PARADIGM-HF trial, we included 3778 patients with known diabetes or an HbA1c≥6·5% at screening out of 8399 patients with HFrEF who were randomly assigned to treatment with sacubitril/valsartan or enalapril. Of these patients, most (98%) had type 2 diabetes. We assessed changes in HbA1c, triglycerides, HDL cholesterol and BMI in a mixed effects longitudinal analysis model. Times to initiation of oral antihyperglycaemic drugs or insulin in subjects previously not treated with these agents were compared between treatment groups. There were no significant differences in HbA1c concentrations between randomised groups at screening. During the first year of follow-up, HbA1c concentrations decreased by 0·16% (SD 1·40) in the enalapril group and 0·26% (SD 1·25) in the sacubitril/valsartan group (between-group reduction 0·13%, 95% CI 0·05–0·22, p=0·0023). HbA1c concentrations were persistently lower in the sacubitril/valsartan group than in the enalapril group over the 3-year follow-up (between-group reduction 0·14%, 95% CI 0·06–0·23, p=0·0055). New use of insulin was 29% lower in patients receiving sacubitril/valsartan (114 [7%] patients) compared with patients receiving enalapril (153 [10%]; hazard ratio 0·71, 95% CI 0·56–0·90, p=0·0052). Similarly, fewer patients were started on oral antihyperglycaemic therapy (0·77, 0·58–1·02, p=0·073) in the sacubitril/valsartan group. Patients with diabetes and HFrEF enrolled in PARADIGM-HF who received sacubitril/valsartan had a greater long-term reduction in HbA1c than those receiving enalapril. These data suggest that sacubitril/valsartan might enhance glycaemic control in patients with diabetes and HFrEF.