Cardiovascular Safety, Long-Term Noncardiovascular Safety, and Efficacy of Sodium-Glucose Cotransporter 2 Inhibitors in Patients With Type 2 Diabetes Mellitus: A Systemic Review and Meta-Analysis With Trial Sequential Analysis.
Cardiovascular Safety, Long-Term Noncardiovascular Safety, and Efficacy of Sodium-Glucose Cotransporter 2 Inhibitors in Patients With Type 2 Diabetes Mellitus: A Systemic Review and Meta-Analysis With Trial Sequential Analysis.
复制标题
钠-葡萄糖协同转运蛋白 2 抑制剂对 2 型糖尿病患者的心血管安全性、长期非心血管安全性和疗效：系统评价和荟萃分析与试验序贯分析
DOI：
10.1161/jaha.117.007165
复制
发表时间：
2018-01-20
影响因子：
5.4
通讯作者：
Xu B
中科院分区：
文献类型：
--
作者：
Zhang XL;Zhu QQ;Chen YH;Li XL;Chen F;Huang JA;Xu B
SGLT 2（钠-葡萄糖协同转运蛋白2）抑制剂的心血管和长期非心血管安全性和疗效尚未得到充分记录。对于心血管结局，我们对随机对照试验和调整后的观察性研究进行了Meta分析和试验序贯分析，每项研究至少随访26周和2000患者年。对于长期非心血管安全性和疗效结局分析，我们仅纳入了至少随访2年和1000患者年的随机对照试验。心血管结局分析纳入了5项研究（351476例患者）。Meta分析显示，SGLT 2抑制剂可显著降低重大心脏不良事件的风险（风险比[HR]：0.80; 95%置信区间[CI]：0.69-0.92; P=0.002），全因死亡率（HR：0.67; 95% CI，0.54-0.84; P<0.001），心血管死亡率（HR：0.77; 95% CI，0.60-0.98; P=0.03），非致死性心肌梗死（HR：0.86; 95% CI，0.76-0.98; P=0.02），因心力衰竭住院（HR：0.62; 95% CI，0.55-0.69; P<0.001），以及白蛋白尿进展（HR：0.68; 95% CI，0.58-0.81; P<0.001）。在非致死性卒中中没有发现显著差异。仅限于随机对照试验的分析显示了类似的结果。试验序贯分析提供了确凿的证据，证明使用SGLT 2抑制剂可使主要不良心脏事件、全因死亡率和心力衰竭住院率降低20%，但心血管死亡率的证据仍不确定。9项随机对照试验有助于长期非心血管和疗效分析。SGLT 2抑制剂降低了低血糖和急性肾损伤的发生率，但增加了尿路和生殖器感染的风险。 SGLT 2抑制剂显示出显著的心血管和肾脏保护作用以及良好的长期非心血管安全性和持续疗效。
The cardiovascular and long‐term noncardiovascular safety and efficacy of SGLT2 (sodium–glucose cotransporter 2) inhibitors have not been well documented. For cardiovascular outcomes, we performed a meta‐analysis with trial sequential analysis of randomized controlled trials and adjusted observational studies, each with a minimum of 26 weeks and 2000 patient‐years of follow‐up. For long‐term noncardiovascular safety and efficacy outcome analyses, we included only randomized controlled trials with at least 2 years and 1000 patient‐years of follow‐up. Five studies with 351 476 patients were included in cardiovascular outcomes analysis. Meta‐analyses showed that SGLT2 inhibitors significantly reduced the risks of major adverse cardiac events (hazard ratio [HR]: 0.80; 95% confidence interval [CI], 0.69–0.92; P=0.002), all‐cause mortality (HR: 0.67; 95% CI, 0.54–0.84; P<0.001), cardiovascular mortality (HR: 0.77; 95% CI, 0.60–0.98; P=0.03), nonfatal myocardial infarction (HR: 0.86; 95% CI, 0.76–0.98; P=0.02), hospitalization for heart failure (HR: 0.62; 95% CI, 0.55–0.69; P<0.001), and progression of albuminuria (HR: 0.68; 95% CI, 0.58–0.81; P<0.001). No significant difference in nonfatal stroke was found. Analyses limited to randomized controlled trials showed similar findings. Trial sequential analysis provided firm evidence of a 20% reduction in major adverse cardiac events, all‐cause mortality, and hospitalization for heart failure with SGLT2 inhibitors, but evidence remains inconclusive for cardiovascular mortality. Nine randomized controlled trials contributed to long‐term noncardiovascular and efficacy analyses. SGLT2 inhibitors reduced incidence of hypoglycemia and acute kidney injury but increased the risks of urinary tract and genital infections. SGLT2 inhibitors showed remarkable cardiovascular‐ and renal‐protective effects and good long‐term noncardiovascular safety with sustained efficacy.