Nasrallah Dima, Abdelhamid Alaa, Tluli Omar, Al-Haneedi Yaman, Dakik Habib, Eid Ali H
College of Medicine, QU Health, Qatar University, P.O. Box 2713, Doha, Qatar.
Division of Cardiology, Department of Internal Medicine, Faculty of Medicine, American University of Beirut, Beirut, Lebanon.
Pharmacol Res. 2024 Jun;204:107210. doi: 10.1016/j.phrs.2024.107210. Epub 2024 May 11.
Heart failure with reduced ejection fraction (HFrEF) is a clinical syndrome characterized by volume overload, impaired exercise capacity, and recurrent hospital admissions. A major contributor to the pathophysiology and clinical presentation of heart failure is the activation of the renin-angiotensin-aldosterone system (RAAS). Normally, RAAS is responsible for the homeostatic regulation of blood pressure, extracellular fluid volume, and serum sodium concentration. In HFrEF, RAAS gets chronically activated in response to decreased cardiac output, further aggravating the congestion and cardiotoxic effects. Hence, inhibition of RAAS is a major approach in the pharmacologic treatment of those patients. The most recently introduced RAAS antagonizing medication class is angiotensin receptor blocker/ neprilysin inhibitor (ARNI). In this paper, we discuss ARNIs' superiority over traditional RAAS antagonizing agents in reducing heart failure hospitalization and mortality. We also tease out the evidence that shows ARNIs' renoprotective functions in heart failure patients including those with chronic or end stage kidney disease. We also discuss the evidence showing the added benefit resulting from combining ARNIs with a sodium-glucose cotransporter-2 (SGLT-2) inhibitor. Moreover, how ARNIs decrease the risk of arrhythmias and reverse cardiac remodeling, ultimately lowering the risk of cardiovascular death, is also discussed. We then present the positive outcome of ARNIs' use in patients with diabetes mellitus and those recovering from acute decompensated heart failure. ARNIs' side effects are also appreciated and discussed. Taken together, the provided insight and critical appraisal of the evidence justifies and supports the implementation of ARNIs in the guidelines for the treatment of HFrEF.
射血分数降低的心力衰竭（HFrEF）是一种临床综合征，其特征为容量超负荷、运动能力受损和反复住院。肾素-血管紧张素-醛固酮系统（RAAS）的激活是心力衰竭病理生理学和临床表现的一个主要促成因素。正常情况下，RAAS负责血压、细胞外液容量和血清钠浓度的稳态调节。在HFrEF中，RAAS会因心输出量减少而长期激活，进一步加重充血和心脏毒性作用。因此，抑制RAAS是这类患者药物治疗的主要方法。最近引入的RAAS拮抗药物类别是血管紧张素受体阻滞剂/中性肽链内切酶抑制剂（ARNI）。在本文中，我们讨论了ARNI在降低心力衰竭住院率和死亡率方面相对于传统RAAS拮抗药物的优势。我们还梳理了显示ARNI对心力衰竭患者（包括慢性或终末期肾病患者）具有肾脏保护作用的证据。我们还讨论了显示ARNI与钠-葡萄糖协同转运蛋白2（SGLT-2）抑制剂联合使用带来额外益处的证据。此外，还讨论了ARNI如何降低心律失常风险并逆转心脏重塑，最终降低心血管死亡风险。然后，我们介绍了ARNI在糖尿病患者和急性失代偿性心力衰竭恢复期患者中的使用阳性结果。我们也认识并讨论了ARNI的副作用。综上所述，对证据的深入分析和批判性评估证明并支持在HFrEF治疗指南中实施ARNI。
