Effect of Dapagliflozin on Atrial Fibrillation in Patients With Type 2 Diabetes Mellitus Insights From the DECLARE-TIMI 58 Trial
Effect of Dapagliflozin on Atrial Fibrillation in Patients With Type 2 Diabetes Mellitus Insights From the DECLARE-TIMI 58 Trial
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DOI：
10.1161/circulationaha.119.044183
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发表时间：
2020-04-14
期刊：
影响因子：
37.8
通讯作者：
Wiviott, Stephen D.
中科院分区：
文献类型：
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作者：
Zelniker, Thomas A.;Bonaca, Marc P.;Wiviott, Stephen D.
背景：心房颤动（AF）和心房扑动（AFL）与糖尿病及其相关合并症（包括高血压、肥胖和心力衰竭[HF]）有关。钠 - 葡萄糖协同转运蛋白2（SGLT2）抑制剂已被证明可降低血压、减轻体重、对左心室重构有益，并减少2型糖尿病患者因心力衰竭住院和心血管死亡。因此，我们研究了SGLT2抑制剂是否也能降低AF/AFL的风险。
方法：DECLARE - TIMI 58（达格列净对心血管事件的影响 - 心肌梗死溶栓治疗58）研究了SGLT2抑制剂达格列净与安慰剂在17160例2型糖尿病患者中的疗效和安全性，这些患者要么有动脉粥样硬化性心血管疾病的多种危险因素（n = 10186），要么已知患有动脉粥样硬化性心血管疾病（n = 6974）。我们分别使用考克斯模型和负二项式模型探讨了达格列净对有（n = 1116）和无既往AF/AFL的患者中首次和总的AF/AFL事件数量的影响。通过使用MedDRA首选术语（“心房颤动”，“心房扑动”）搜索安全数据库来确定AF/AFL事件。
结果：达格列净使AF/AFL事件的风险降低了19%（264例对325例事件；每1000患者 - 年7.8例对9.6例事件；风险比[HR]，0.81[95%置信区间，0.68 - 0.95]；P = 0.009）。无论基线时有无AF/AFL病史，AF/AFL事件的减少是一致的（既往AF/AFL：HR，0.79[95%置信区间，0.58 - 1.09]；无AF/AFL：HR，0.81[95%置信区间，0.67 - 0.98]；交互作用P值为0.89）。同样，存在动脉粥样硬化性心血管疾病（HR，0.83[95%置信区间，0.66 - 1.04]）与多种危险因素（HR，0.78[95%置信区间，0.62 - 0.99]；交互作用P值为0.72）或有心力衰竭病史（HF：HR，0.78[95%置信区间，0.55 - 1.11]；无HF：HR，0.81[95%置信区间，0.68 - 0.97]；交互作用P值为0.88）并没有改变达格列净所致的AF/AFL事件减少情况。此外，性别、缺血性卒中病史、糖化血红蛋白A(1c)、体重指数、血压或估计的肾小球滤过率均未改变这种效应（所有交互作用P值>0.20）。达格列净还减少了AF/AFL事件（首次和复发）的总数（337例对432例；发生率比，0.77[95%置信区间，0.64 - 0.92]；P = 0.005）。
结论：达格列净降低了2型糖尿病高危患者中报告的AF/AFL不良事件发作的发生率。无论患者既往有无AF病史、动脉粥样硬化性心血管疾病或HF，这种效应都是一致的。
注册：网址：；唯一标识符：NCT01730534
Background:Atrial fibrillation (AF) and atrial flutter (AFL) are associated with both diabetes mellitus and its related comorbidities, including hypertension, obesity, and heart failure (HF). SGLT2 (sodium-glucose cotransporter 2) inhibitors have been shown to lower blood pressure, reduce weight, have salutary effects on left ventricular remodeling, and reduce hospitalization for HF and cardiovascular death in patients with type 2 diabetes mellitus. We therefore investigated whether SGLT2 inhibitors could also reduce the risk of AF/AFL.Methods:DECLARE-TIMI 58 (Dapagliflozin Effect on Cardiovascular Events-Thrombolysis in Myocardial Infarction 58) studied the efficacy and safety of the SGLT2 inhibitor dapagliflozin versus placebo in 17 160 patients with type 2 diabetes mellitus and either multiple risk factors for atherosclerotic cardiovascular disease (n=10 186) or known atherosclerotic cardiovascular disease (n=6974). We explored the effect of dapagliflozin on the first and total number of AF/AFL events in patients with (n=1116) and without prevalent AF/AFL using Cox and negative binomial models, respectively. AF/AFL events were identified by search of the safety database using MedDRA preferred terms ("atrial fibrillation," "atrial flutter").Results:Dapagliflozin reduced the risk of AF/AFL events by 19% (264 versus 325 events; 7.8 versus 9.6 events per 1000 patient-years; hazard ratio [HR], 0.81 [95% CI, 0.68-0.95]; P=0.009). The reduction in AF/AFL events was consistent regardless of presence or absence of a history of AF/AFL at baseline (previous AF/AFL: HR, 0.79 [95% CI, 0.58-1.09]; no AF/AFL: HR, 0.81 [95% CI, 0.67-0.98]; P for interaction 0.89). Similarly, presence of atherosclerotic cardiovascular disease (HR, 0.83 [95% CI, 0.66-1.04]) versus multiple risk factors (HR, 0.78 [95% CI, 0.62-0.99]; P for interaction 0.72) or a history of HF (HF: HR, 0.78 [95% CI, 0.55-1.11]; No HF: HR, 0.81 [95% CI, 0.68-0.97]; P for interaction 0.88) did not modify the reduction in AF/AFL events observed with dapagliflozin. Moreover, there was no effect modification by sex, history of ischemic stroke, glycated hemoglobin A(1c), body mass index, blood pressure, or estimated glomerular filtration rate (all P for interaction >0.20). Dapagliflozin also reduced the total number (first and recurrent) of AF/AFL events (337 versus 432; incidence rate ratio, 0.77 [95% CI, 0.64-0.92]; P=0.005).Conclusions:Dapagliflozin decreased the incidence of reported episodes of AF/AFL adverse events in high-risk patients with type 2 diabetes mellitus. This effect was consistent regardless of the patient's previous history of AF, atherosclerotic cardiovascular disease, or HF.Registration:URL: ; Unique identifier: NCT01730534.