Kaplinsky Edgardo
Cardiology Unit, Medicine Department, Hospital Municipal de Badalona, Spain.
Drugs Context. 2020 Feb 28;9. doi: 10.7573/dic.2019-11-3. eCollection 2020.
Heart failure (HF) continues to be a major global health problem with a notable impact in terms of morbidity and mortality and so, in consequence, with a large unmet necessity for new therapies. The inhibition of sodium-glucose cotransporter 2 (SGLT2) causes glycosuria and natriuresis, leading to reductions in hyperglycemia (antidiabetic effect), body weight, and blood pressure. In this context, outcome trials have been shown to reduce hospitalizations for HF in patients with type 2 diabetes mellitus treated with SGLT2 inhibitors. The underlying protective cardiovascular (CV) mechanisms of these agents are complex, multifactorial, and not entirely understood as, in addition to a diuretic-like function, SGLT2 inhibitors may mitigate glycemic-related toxicity, promote ketogenesis, increase hematocrit, and exert antihypertrophic, antifibrotic, and antiremodeling properties. The DAPA-HF (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure) trial enrolled 4744 patients with HF and reduced ejection fraction (EF) who were receiving excellent guideline-directed treatment before the addition of dapagliflozin (a SGLT2 inhibitor) or placebo. The DAPA-HF trial clearly showed that dapagliflozin was superior to placebo at preventing CV deaths and HF events. The relative and absolute risk reductions in death and hospitalizations were consistent across subgroups including patients with and without diabetes; so, in consequence, dapagliflozin represents the first in a new class of drug for HF with reduced EF. The recently published Dapagliflozin Effects on Biomarkers, Symptoms, and Functional Status in Patients With Heart Failure With Reduced Ejection Fraction (DEFINE-HF) trial is also described in this review as well as the thought-to-be mechanisms of action of SGLT2 inhibitors beyond their known glucose-lowering effects. There is a vast, ambitious, and promising ongoing clinical investigation program with dapagliflozin and other SGLT2 inhibitors, which may result in changes to the therapeutic approach to HF in a relatively short time.
心力衰竭（HF）仍然是一个重大的全球健康问题，在发病率和死亡率方面具有显著影响，因此，对新疗法存在巨大的未满足需求。抑制钠-葡萄糖协同转运蛋白2（SGLT2）会导致糖尿和利钠，从而降低高血糖（抗糖尿病作用）、体重和血压。在这种背景下，结果试验表明，SGLT2抑制剂治疗的2型糖尿病患者因HF住院的情况有所减少。这些药物潜在的心血管（CV）保护机制复杂、多因素且尚未完全明确，因为除了类似利尿剂的功能外，SGLT2抑制剂可能减轻血糖相关毒性、促进生酮作用、增加血细胞比容，并具有抗肥厚、抗纤维化和抗重塑特性。DAPA-HF（达格列净与心力衰竭不良结局预防）试验纳入了4744例HF且射血分数（EF）降低的患者，这些患者在加用达格列净（一种SGLT2抑制剂）或安慰剂之前接受了出色的指南指导治疗。DAPA-HF试验清楚地表明，在预防CV死亡和HF事件方面，达格列净优于安慰剂。在包括有糖尿病和无糖尿病的患者在内的各亚组中，死亡和住院的相对及绝对风险降低情况是一致的；因此，达格列净代表了一类新型的用于EF降低的HF药物中的首个药物。本综述还描述了最近发表的达格列净对射血分数降低的心力衰竭患者生物标志物、症状和功能状态的影响（DEFINE-HF）试验，以及SGLT2抑制剂超出其已知降糖作用的潜在作用机制。目前正在进行一项关于达格列净和其他SGLT2抑制剂的庞大、宏伟且前景广阔的临床研究计划，这可能在相对较短的时间内导致HF治疗方法的改变。
