Cahn Avivit, Wiviott Stephen D, Mosenzon Ofri, Goodrich Erica L, Murphy Sabina A, Yanuv Ilan, Rozenberg Aliza, Bhatt Deepak L, Leiter Lawrence A, McGuire Darren K, Wilding John P H, Gause-Nilsson Ingrid A M, Langkilde Anna Maria, Sabatine Marc S, Raz Itamar
Diabetes Unit, Department of Endocrinology and Metabolism, Hadassah Medical Center, The Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel.
TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
Diabetes Care. 2022 Apr 1;45(4):938-946. doi: 10.2337/dc21-1744.
Current guidelines recommend prescribing SGLT2 inhibitors to patients with type 2 diabetes and established or at high risk for atherosclerotic cardiovascular disease (ASCVD), irrespective of HbA1c levels. We studied the association of HbA1c with cardiovascular and renal outcomes and whether the benefit of dapagliflozin varies by baseline HbA1c.
In the Dapagliflozin Effect on Cardiovascular Events trial (DECLARE-TIMI 58), 17,160 patients with type 2 diabetes were randomly assigned to dapagliflozin or placebo for a median follow-up of 4.2 years. Cardiovascular and renal outcomes by baseline HbA1c in the overall population and with dapagliflozin versus placebo in HbA1c subgroups were studied by Cox regression models.
In the overall population, higher baseline HbA1c was associated with a higher risk of cardiovascular death or hospitalization for heart failure (HHF); major adverse cardiovascular events (MACE), including cardiovascular death, myocardial infarction, and ischemic stroke; and cardiorenal outcomes (adjusted hazard ratios 1.12 [95% CI 1.06-1.19], 1.08 [1.04-1.13], and 1.17 [1.11-1.24] per 1% higher level, respectively). Elevated HbA1c was associated with a greater increased risk for MACE and cardiorenal outcomes in patients with multiple risk factors (MRF) than in established ASCVD (P-interaction = 0.0064 and 0.0093, respectively). Compared with placebo, dapagliflozin decreased the risk of cardiovascular death/HHF, HHF, and cardiorenal outcomes, with no heterogeneity by baseline HbA1c (P-interaction > 0.05).
Higher HbA1c levels were associated with greater cardiovascular and renal risk, particularly in the MRF population, yet the benefits of dapagliflozin were observed in all subgroups irrespective of baseline HbA1c, including patients with HbA1c <7%.
当前指南建议，无论糖化血红蛋白（HbA1c）水平如何，均应给患有2型糖尿病且已确诊或有动脉粥样硬化性心血管疾病（ASCVD）高风险的患者开具钠-葡萄糖协同转运蛋白2（SGLT2）抑制剂。我们研究了HbA1c与心血管及肾脏结局的关联，以及达格列净的获益是否因基线HbA1c水平而异。
在达格列净对心血管事件的影响试验（DECLARE-TIMI 58）中，17160例2型糖尿病患者被随机分配至达格列净组或安慰剂组，中位随访4.2年。通过Cox回归模型研究总体人群中按基线HbA1c水平划分的心血管和肾脏结局，以及在HbA1c亚组中达格列净组与安慰剂组的相关结局。
在总体人群中，较高的基线HbA1c与心血管死亡或因心力衰竭住院（HHF）风险较高相关；与主要不良心血管事件（MACE，包括心血管死亡、心肌梗死和缺血性卒中）相关；与心肾结局相关（每升高1%，调整后的风险比分别为1.12 [95%置信区间1.06 - 1.19]、1.08 [1.04 - 1.13]和1.17 [1.11 - 1.24]）。与已确诊的ASCVD患者相比，糖化血红蛋白升高与多危险因素（MRF）患者发生MACE和心肾结局的风险增加幅度更大（交互P值分别为0.0064和0.0093）。与安慰剂相比，达格列净降低了心血管死亡/HHF、HHF和心肾结局的风险，且按基线HbA1c水平无异质性（交互P值>0.05）。
较高的HbA1c水平与更大的心血管和肾脏风险相关，尤其是在多危险因素人群中，但无论基线HbA1c如何，在所有亚组中均观察到达格列净的获益，包括HbA1c<7%的患者。
