Tolerability and safety barriers to sodium-glucose cotransporter 2 inhibitor initiation in heart failure with reduced ejection fraction.
Tolerability and safety barriers to sodium-glucose cotransporter 2 inhibitor initiation in heart failure with reduced ejection fraction.
复制标题
射血分数降低的心力衰竭患者启动钠-葡萄糖协同转运蛋白 2 抑制剂的耐受性和安全性障碍。
DOI：
10.1002/ejhf.2633
复制
发表时间：
2022
影响因子：
18.2
通讯作者：
Fudim,Marat
中科院分区：
文献类型：
--
作者：
Salah,HusamM;Fudim,Marat
尽管有可靠的数据支持使用心力衰竭（HF）疾病改善四联疗法，（β-阻断剂;血管紧张素转换酶抑制剂[ACEIs]、血管紧张素受体阻断剂[ARB]或血管紧张素受体脑啡肽酶抑制剂[ARNI];盐皮质激素受体拮抗剂;和钠-葡萄糖协同转运蛋白2 [SGLT 2]抑制剂），以降低因HF而死亡和住院的风险，在HF住院的上升趋势中，多因素的次优临床指南依从性持续存在。（1，2）启动这些救生药物的失败，部分原因是由于对耐受性和安全性的担忧。虽然个体临床试验通常显示SGLT 2抑制剂在HF中具有良好的安全性和耐受性特征，但目前的荟萃分析证据水平主要由不完全是HF患者的队列生成，射血分数降低（HFrEF）的HF患者的荟萃分析安全性证据更有限。（3，4）HF人群是一个异常脆弱的人群，倾向于患有多种合并症，这些合并症累积起来会导致脆弱的临床状态，其中血流动力学的微小变化可能会导致临床上明显的不良变化。渗透性利尿和尿钠排泄导致的血浆容量减少是SGLT 2抑制剂有利HF结局的拟定机制之一。(5)然而，该途径可能导致容量稳态的变化，并可能导致血管内容量不足、低血压和急性肾损伤（阿基）。在急性HF患者或近期因HF住院的患者中开始使用SGLT 2抑制剂时，由于其临床状态脆弱且同时使用高剂量袢利尿剂，这种担忧变得更加严重。
Despite robust data supporting the use of the heart failure (HF) disease-modifying quadruple therapy (beta-blockers; angiotensin-converting enzyme inhibitors [ACEIs], angiotensin receptor blockers [ARBs], or angiotensin receptor–neprilysin inhibitors [ARNIs]; mineralocorticoid receptor antagonists; and sodium-glucose cotransporter 2 [SGLT2] inhibitors) to decrease the risk of mortality and hospitalization for HF, a multifactorial suboptimal clinical guideline compliance persists amid uprising trend of HF hospitalization.(1, 2) Failure of initiating these lifesaving medications, in part, stems from concerns related tolerability and safety. While individual clinical trials have generally shown a good safety and tolerability profile for SGLT2 inhibitors in HF, the current meta-analytic level of evidence is mostly generated by cohorts that were not exclusively HF patients with even more limited meta-analytic safety evidence in patients with HF with reduced ejection fraction (HFrEF).(3, 4) The HF population is an exceptionally fragile population with a tendency to have several comorbidities that cumulatively result in a tenuous clinical status, in which a small change in their hemodynamics may result in clinically evident adverse changes. Plasma volume reduction by osmotic diuresis and natriuresis is one the proposed mechanisms that underlie the favorable HF outcomes of SGLT2 inhibitors.(5) However, this pathway can potentially result in a shift in volume homeostasis with potential intravascular volume depletion, hypotension, and acute kidney injury (AKI). This concern becomes heightened when initiating SGLT2 inhibitors in patients with acute HF or those with recent hospitalization for HF given their clinically tenuous status and concurrent use of high doses of loop diuretics.