Cardiovascular Outcomes and Risks After Initiation of a Sodium Glucose Cotransporter 2 Inhibitor: Results From the EASEL Population-Based Cohort Study (Evidence for Cardiovascular Outcomes With Sodium Glucose Cotransporter 2 Inhibitors in the Real World).
Cardiovascular Outcomes and Risks After Initiation of a Sodium Glucose Cotransporter 2 Inhibitor: Results From the EASEL Population-Based Cohort Study (Evidence for Cardiovascular Outcomes With Sodium Glucose Cotransporter 2 Inhibitors in the Real World).
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DOI：
10.1161/circulationaha.117.031227
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发表时间：
2018-04-03
期刊：
影响因子：
37.8
通讯作者：
Rosenthal N
中科院分区：
文献类型：
--
作者：
Udell JA;Yuan Z;Rush T;Sicignano NM;Galitz M;Rosenthal N
补充数字内容可在文本中找到。临床试验已显示钠葡萄糖协同转运蛋白2抑制剂（SGLT 2 i）的心血管获益和潜在风险。试验可能无法解决个体终点或安全性问题。我们在2013年4月1日至2016年12月31日期间美国国防部军事卫生系统内新开始使用降糖药的2型糖尿病伴心血管疾病患者中进行了一项基于人群的队列研究。使用条件性考克斯模型比较新SGLT 2 i使用者与其他降糖药物，评价至首个复合终点（全因死亡和因心力衰竭事件住院）、重大心血管不良事件（定义为全因死亡、非致死性心肌梗死和非致死性卒中）和单个终点的时间的发生率、风险比（HR）和95%置信区间（CI）。探索性安全终点是膝下下肢截肢。进行意向治疗和治疗中分析。在倾向匹配后，对25258例患者进行了中位1.6年的随访。与非SGLT 2 i相比，开始SGLT 2 i治疗与全因死亡率和心力衰竭住院率降低相关（1.73 vs 3.01起事件/100人-年; HR，0.57; 95% CI，0.50-0.65）和主要心血管不良事件（2.31 vs 3.45起事件/100人-年; HR，0.67; 95% CI，0.60-0.75）。开始SGLT 2 i治疗还与膝下下肢截肢风险增加1.2倍相关（0.17 vs 0.09起事件/100人-年; HR，1.99; 95% CI，1.12-3.51）。由于数据库中的卡格列净暴露量不成比例，因此在卡格列净组观察到大多数截肢。治疗中分析的结果一致。在该高风险队列中，开始SGLT 2 i治疗与全因死亡、因心力衰竭住院和重大不良心血管事件的风险降低以及膝下下肢截肢的风险升高相关。研究结果强调了启动SGLT 2 i时需要注意的潜在获益和风险。目前尚不清楚膝下下肢截肢的风险是否会在整个药物类别中延伸，因为该研究没有把握在个体治疗之间进行比较。
Supplemental Digital Content is available in the text. Clinical trials have shown cardiovascular benefits and potential risks from sodium glucose cotransporter 2 inhibitors (SGLT2i). Trials may have limited ability to address individual end points or safety concerns. We performed a population-based cohort study among patients with type 2 diabetes mellitus with established cardiovascular disease newly initiated on antihyperglycemic agents within the US Department of Defense Military Health System between April 1, 2013, and December 31, 2016. Incidence rates, hazard ratios (HRs), and 95% confidence intervals (CIs) for time to first composite end point of all-cause mortality and hospitalization for heart failure event, major adverse cardiovascular events (defined as all-cause mortality, nonfatal myocardial infarction, and nonfatal stroke), and individual end points were evaluated using conditional Cox models comparing new SGLT2i users with other antihyperglycemic agents. The exploratory safety end point was below-knee lower extremity amputation. Intent-to-treat and on-treatment analyses were performed. After propensity matching, 25 258 patients were followed for a median of 1.6 years. Compared with non-SGLT2i, initiation of SGLT2i was associated with a lower rate of all-cause mortality and hospitalization for heart failure (1.73 versus 3.01 events per 100 person-years; HR, 0.57; 95% CI, 0.50–0.65) and major adverse cardiovascular events (2.31 versus 3.45 events per 100 person-years; HR, 0.67; 95% CI, 0.60–0.75). SGLT2i initiation was also associated with an ≈2-fold higher risk of below-knee lower extremity amputation (0.17 versus 0.09 events per 100 person-years; HR, 1.99; 95% CI, 1.12–3.51). Because of the disproportionate canagliflozin exposure in the database, the majority of amputations were observed on canagliflozin. Results were consistent in the on-treatment analysis. In this high-risk cohort, initiation of SGLT2i was associated with lower risk of all-cause mortality, hospitalization for heart failure, and major adverse cardiovascular events and higher risk of below-knee lower extremity amputation. Findings underscore the potential benefit and risks to be aware of when initiating SGLT2i. It remains unclear whether the below-knee lower extremity amputation risk extends across the class of medication, because the study was not powered to make comparisons among individual treatments.