Kluger Aaron Y, Tecson Kristen M, Barbin Clay M, Lee Andy Y, Lerma Edgar V, Rosol Zachary P, Rangaswami Janani, Lepor Norman E, Cobble Michael E, McCullough Peter A
Baylor Heart and Vascular Institute, Dallas, TX, 75226.
Baylor Scott & White Research Institute, Dallas, TX, 75226.
Rev Cardiovasc Med. 2018 Jun 30;19(2):41-49. doi: 10.31083/j.rcm.2018.02.907.
In this systematic review, we sought to summarize the 3 recent sodium-glucose cotransporter 2 inhibitor (SGLT2i) trials (Dapagliflozin Effect on CardiovasculAR Events (DECLARE-TIMI 58), Canagliflozin Cardiovascular Assessment Study (CANVAS) Program, and Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes (EMPA-REG OUTCOME)) and to explore the potential causes for their different results. We found that the major adverse cardiovascular event rates per 1000 patient-years for drug and placebo, as well as the corresponding relative risk reductions, were 22.6, 24.2, 7%; 26.9, 31.5, 14%; 37.4, 43.9, 14% for DECLARE-TIMI 58, CANVAS, and EMPA-REG OUTCOME, respectively. DECLARETIMI 58 had the fewest cardiorenal events (across treatment and control arms) and EMPA-REG OUTCOME the most. DECLARE-TIMI 58 used alternative inclusion criterion for baseline renal function (creatinine clearance ≧ 60 mL/min) compared to the other trials (estimated glomerular filtration rate (eGFR) > 30 mL/min/1.73 m bodysurface area). Therefore, the DECLARE-TIMI 58 study cohort had higher eGFR (mean eGFR 85.2 mL/min/1.73 m compared to 76.5 and 74 in CANVAS and EMPAREG OUTCOME, respectively); this may have caused the difference in results. Additionally contributing to the high event rate in EMPA-REG OUTCOME was the requirement of prior confirmed cardiovascular disease (CVD), resulting in 99.2% of patients with CVD compared to only 65.6% and 40.6% in CANVAS and DECLARE-TIMI 58, respectively (which did not require CVD). In conclusion, there is a need for large-scale studies of SGLT2i with matching inclusion/exclusion criteria and appropriate endpoints to ensure a truly direct comparison of the drugs.
在本系统评价中，我们试图总结最近的3项钠-葡萄糖协同转运蛋白2抑制剂（SGLT2i）试验（达格列净对心血管事件的影响（DECLARE-TIMI 58）、卡格列净心血管评估研究（CANVAS）项目以及恩格列净、2型糖尿病患者的心血管结局和死亡率（EMPA-REG OUTCOME）），并探讨其结果不同的潜在原因。我们发现，DECLARE-TIMI 58、CANVAS和EMPA-REG OUTCOME中，每1000患者年药物组和安慰剂组的主要不良心血管事件发生率以及相应的相对风险降低率分别为22.6、24.2、7%；26.9、31.5、14%；37.4、43.9、14%。DECLARE-TIMI 58的心脏肾脏事件最少（治疗组和对照组均如此），而EMPA-REG OUTCOME最多。与其他试验（估计肾小球滤过率（eGFR）>30 mL/min/1.73 m²体表面积）相比，DECLARE-TIMI 58对基线肾功能采用了不同的纳入标准（肌酐清除率≧60 mL/min）。因此，DECLARE-TIMI 58研究队列的eGFR更高（平均eGFR为85.2 mL/min/1.73 m²，而CANVAS和EMPA-REG OUTCOME分别为76.5和74）；这可能导致了结果的差异。此外，EMPA-REG OUTCOME事件发生率高的另一个原因是要求患者先前确诊患有心血管疾病（CVD），该试验中99.2%的患者患有CVD，而CANVAS和DECLARE-TIMI 58分别仅为65.6%和40.6%（后两者不要求患有CVD）。总之，需要开展大规模研究，采用匹配的纳入/排除标准和合适的终点，以确保对这些药物进行真正直接的比较。
