Division of Cardiology, Medical University of Vienna, Vienna, Austria.
TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Eur J Heart Fail. 2021 Jun;23(6):1026-1036. doi: 10.1002/ejhf.2073. Epub 2020 Dec 29.
Dapagliflozin reduced the risk of the composite of cardiovascular (CV) death or hospitalization for heart failure (HHF) in patients with type 2 diabetes mellitus in DECLARE-TIMI 58. We hypothesized that baseline N-terminal pro B-type natriuretic peptide (NT-proBNP) and high-sensitivity troponin T (hsTnT) levels would help identify patients who are at higher baseline risk and we describe the treatment effects of dapagliflozin in patients according to their baseline NT-proBNP and hsTnT levels.
This was a pre-specified biomarker study from DECLARE-TIMI 58, a randomized, double-blind, placebo-controlled CV outcomes trial of dapagliflozin. Baseline NT-proBNP and hsTnT levels were measured in the TIMI Clinical Trials Laboratory in 14 565 patients. Among the included patients, 9143 patients (62.8%) were male, 1464 (10.1%) had a history of heart failure and the mean age was 63.9 years. The median baseline NT-proBNP and hsTnT levels were 75 pg/mL [interquartile range (IQR) 35-165] and 10.2 pg/mL (IQR 6.9-15.5), respectively. Patients with higher NT-proBNP and hsTnT quartiles had higher rates of CV death/HHF (Q4 vs. Q1: NT-proBNP: 4-year Kaplan-Meier event rates 13.7% vs. 1.0%; hsTnT: 11.8% vs. 1.4%; P-trend <0.001). Dapagliflozin consistently reduced the relative risk of CV death/HHF regardless of baseline NT-proBNP (P-interaction 0.72) or hsTnT quartiles (P-interaction 0.93). Given their higher baseline risk, patients with NT-proBNP and/or hsTnT levels above the median derived larger absolute risk reductions with dapagliflozin (NT-proBNP 1.9% vs. 0%, P-interaction 0.010; hsTnT 1.8% vs. 0.1%, P-interaction 0.026).
Patients with type 2 diabetes mellitus and higher NT-proBNP or hsTnT levels are at increased risk of CV death and HHF. Dapagliflozin reduced the relative risk of CV death/HHF irrespective of NT-proBNP and hsTnT levels, with greater absolute risk reductions seen in patients with higher baseline biomarker levels.
在 DECLARE-TIMI 58 中，达格列净降低了 2 型糖尿病患者心血管（CV）死亡或因心力衰竭（HHF）住院的复合终点风险。我们假设基线 N 端脑利钠肽前体（NT-proBNP）和高敏肌钙蛋白 T（hsTnT）水平有助于识别基线风险更高的患者，我们根据患者的基线 NT-proBNP 和 hsTnT 水平描述了达格列净的治疗效果。
这是 DECLARE-TIMI 58 的一项预先指定的生物标志物研究，是一项达格列净随机、双盲、安慰剂对照的 CV 结局试验。14565 例患者在 TIMI 临床试验实验室中测量了基线 NT-proBNP 和 hsTnT 水平。在纳入的患者中，9143 例（62.8%）为男性，1464 例（10.1%）有心力衰竭史，平均年龄为 63.9 岁。中位基线 NT-proBNP 和 hsTnT 水平分别为 75pg/ml [四分位距（IQR）35-165]和 10.2pg/ml（IQR 6.9-15.5）。NT-proBNP 和 hsTnT 四分位数较高的患者 CV 死亡/心力衰竭发生率更高（Q4 与 Q1：NT-proBNP：4 年 Kaplan-Meier 事件发生率 13.7% vs. 1.0%；hsTnT：11.8% vs. 1.4%；P 趋势 <0.001）。达格列净可降低 CV 死亡/心力衰竭的相对风险，与基线 NT-proBNP 无关（P 交互作用 0.72）或 hsTnT 四分位数（P 交互作用 0.93）。由于基线风险较高，NT-proBNP 和/或 hsTnT 水平高于中位数的患者接受达格列净治疗的绝对风险降低更大（NT-proBNP 1.9% vs. 0%，P 交互作用 0.010；hsTnT 1.8% vs. 0.1%，P 交互作用 0.026）。
2 型糖尿病患者 NT-proBNP 或 hsTnT 水平较高者发生 CV 死亡和 HHF 的风险增加。达格列净降低了 CV 死亡/心力衰竭的相对风险，与 NT-proBNP 和 hsTnT 水平无关，基线生物标志物水平较高的患者绝对风险降低更大。
