LMC Diabetes and Endocrinology, Brampton, Ontario, Canada.
Leadership Sinai Center for Diabetes, Mount Sinai Hospital, Toronto, Ontario, Canada.
Diabetes Obes Metab. 2020 Jul;22(7):1122-1131. doi: 10.1111/dom.14011. Epub 2020 Mar 12.
To investigate whether the cardiovascular and renal benefits observed with dapagliflozin in the DECLARE-TIMI 58 trial are also observed in patients with short and long-standing diabetes.
This post hoc analysis studied the dual primary efficacy endpoints, a composite of cardiovascular death or hospitalization for heart failure (CVD/HHF) and major adverse cardiovascular events (MACE; CVD, myocardial infarction [MI], ischaemic stroke) by diabetes duration.
Of the 17 160 patients, 3836 had diabetes duration of ≤5 years, 4731 >5-10 years, 3952 >10-15 years, 2433 >15-20 years and 2206 >20 years. Dapagliflozin reduced the risk of CVD/HHF by a similar amount across diabetes duration subgroups, ranging from HR 0.79 (0.58-1.06) in patients with diabetes duration of ≤5 years to 0.75 (0.55-1.03) in those patients with diabetes duration of >20 years (interaction trend P-value 0.76). Hazard ratios (HRs) for MACE ranged from 1.08 (0.87-1.35) in patients with diabetes duration of ≤5 years to 0.67 (0.52-0.86) in those patients with diabetes duration of >20 years (interaction trend P-value 0.004). This was driven by greater reductions in the risk of MI and ischaemic stroke with dapagliflozin in patients with long-standing diabetes (interaction trend P-values 0.019 and 0.015, respectively). The duration-based MACE heterogeneity was apparent in those with or without a history of prior MI and in those with multiple risk factors. The renal-specific outcome was reduced with dapagliflozin with HRs ranging from 0.79 (0.47-1.34) in patients with diabetes duration of ≤5 years to 0.42 (0.25-0.72) in those patients with diabetes duration of >20 years (interaction trend P-value 0.084).
Dapagliflozin reduced the risk of CVD/HHF consistently, regardless of diabetes duration, whereas the treatment effect for MACE differed by duration subgroups, with significant reductions with dapagliflozin in patients with long-standing diabetes.
研究达格列净在DECLARE-TIMI 58 试验中观察到的心血管和肾脏益处是否也存在于糖尿病病程较短和较长的患者中。
本事后分析根据糖尿病病程研究了双重主要疗效终点，即心血管死亡或心力衰竭住院（CVD/HHF）和主要不良心血管事件（MACE；CVD、心肌梗死[MI]、缺血性卒中）的复合终点。
在 17160 名患者中，3836 名患者的糖尿病病程≤5 年，4731 名患者的糖尿病病程>5-10 年，3952 名患者的糖尿病病程>10-15 年，2433 名患者的糖尿病病程>15-20 年，2206 名患者的糖尿病病程>20 年。达格列净降低 CVD/HHF 的风险在糖尿病病程亚组中大致相当，糖尿病病程≤5 年的患者 HR 为 0.79（0.58-1.06），糖尿病病程>20 年的患者 HR 为 0.75（0.55-1.03）（交互趋势 P 值为 0.76）。MACE 的风险比（HR）范围为糖尿病病程≤5 年的患者为 1.08（0.87-1.35），糖尿病病程>20 年的患者为 0.67（0.52-0.86）（交互趋势 P 值为 0.004）。这是由于在病程较长的糖尿病患者中，达格列净降低了 MI 和缺血性卒中的风险（交互趋势 P 值分别为 0.019 和 0.015）。基于病程的 MACE 异质性在有或无既往 MI 病史的患者以及有多种危险因素的患者中均明显。达格列净降低了肾脏特异性结局的风险，HR 范围为糖尿病病程≤5 年的患者为 0.79（0.47-1.34），糖尿病病程>20 年的患者为 0.42（0.25-0.72）（交互趋势 P 值为 0.084）。
达格列净降低 CVD/HHF 的风险是一致的，与糖尿病病程无关，而 MACE 的治疗效果因病程亚组而异，在病程较长的糖尿病患者中，达格列净显著降低 MACE 风险。
