Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Endocrinology, Diabetes, and Hypertension Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Lancet Diabetes Endocrinol. 2017 May;5(5):333-340. doi: 10.1016/S2213-8587(17)30087-6. Epub 2017 Mar 18.
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 HbA 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 HbA ≥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 HbA, triglycerides, HDL cholesterol and BMI in a mixed effects longitudinal analysis model. Time 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 HbA concentrations between randomised groups at screening. During the first year of follow-up, HbA 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). HbA 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 HbA than those receiving enalapril. These data suggest that sacubitril/valsartan might enhance glycaemic control in patients with diabetes and HFrEF.
Novartis.
糖尿病是心力衰竭进展的独立危险因素。沙库巴曲缬沙坦，一种血管紧张素受体-脑啡肽酶抑制剂，与血管紧张素转换酶抑制剂依那普利相比，可改善射血分数降低的心力衰竭（HFrEF）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。我们旨在研究沙库巴曲缬沙坦与依那普利对 HFrEF 合并糖尿病患者的糖化血红蛋白（HbA）和首次使用胰岛素或口服降糖药时间的影响。
在 PARADIGM-HF 试验的事后分析中，我们纳入了 8399 例 HFrEF 患者中的 3778 例已知患有糖尿病或筛选时 HbA≥6.5%的患者，这些患者被随机分配接受沙库巴曲缬沙坦或依那普利治疗。这些患者中，大多数（98%）患有 2 型糖尿病。我们使用混合效应纵向分析模型评估 HbA、甘油三酯、高密度脂蛋白胆固醇和 BMI 的变化。比较两组之间先前未接受这些药物治疗的患者开始使用口服降糖药或胰岛素的时间。
两组患者在筛选时的 HbA 浓度无显著差异。在随访的第一年，依那普利组 HbA 浓度下降 0.16%（SD 1.40），沙库巴曲缬沙坦组下降 0.26%（SD 1.25）（组间降幅 0.13%，95%CI 0.05-0.22，p=0.0023）。在 3 年的随访中，沙库巴曲缬沙坦组的 HbA 浓度持续低于依那普利组（组间降幅 0.14%，95%CI 0.06-0.23，p=0.0055）。接受沙库巴曲缬沙坦治疗的患者新使用胰岛素的比例（114[7%]例）比接受依那普利治疗的患者（153[10%]例）低 29%（风险比 0.71，95%CI 0.56-0.90，p=0.0052）。同样，沙库巴曲缬沙坦组开始使用口服降糖药的患者也更少（0.77，0.58-1.02，p=0.073）。
PARADIGM-HF 中纳入的患有 HFrEF 和糖尿病的患者接受沙库巴曲缬沙坦治疗后，HbA 的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，沙库巴曲缬沙坦可能增强 HFrEF 合并糖尿病患者的血糖控制。
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