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降低高血压及减轻高血压靶器官损害的新型药物。

Newer Drugs to Reduce High Blood Pressure and Mitigate Hypertensive Target Organ Damage.

作者信息

Upadhya Bharathi, Kozak Patrick M, Stacey Richard Brandon, Vasan Ramachandran S

机构信息

Cardiovascular Medicine Section, Department of Internal Medicine, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC, 27157-1045, USA.

Department of Medicine, Sections of Preventative Medicine and Epidemiology and Cardiovascular Medicine, Boston University School of Medicine, Department of Epidemiology, Boston University School of Public Health, Boston, MA, USA.

出版信息

Curr Hypertens Rep. 2022 Jan;24(1):1-20. doi: 10.1007/s11906-022-01166-9. Epub 2022 Feb 14.

Abstract

PURPOSE OF REVIEW

This review aims to investigate the blood pressure (BP)-lowering effects of emerging drugs developed to treat diabetic kidney disease and heart failure (HF). We summarize the potential pathophysiological mechanisms responsible for mitigating hypertensive target organ damage and evaluating the available clinical data on these newer drugs.

RECENT FINDINGS

Nonsteroidal dihydropyridine-based mineralocorticoid receptor antagonists (MRAs), dual angiotensin II receptor-neprilysin inhibitors (valsartan with sacubitril), sodium-glucose cotransporter 2 inhibitors (SGLT2i), and soluble guanylate cyclase stimulators are new classes of chemical agents that have distinct mechanisms of action and have been shown to be effective for the treatment of cardiovascular (CV) disease (CVD), HF, and type 2 diabetes mellitus (T2D). These drugs can be used either alone or in combination with other antihypertensive and CV drugs. Among these, SGLT2i and valsartan with sacubitril offer new avenues to reduce CVD mortality. SGLT2i have a mild-to-moderate effect on BP lowering with a favorable effect on CV and renal hemodynamics and have been shown to produce a significant reduction in the incidence of major adverse CVD events (as monotherapy or add-on therapy) compared with controls (placebo or non-SGLT2i treatment). Most of the participants in these studies had hypertension (HTN) at baseline and were receiving antihypertensive therapy, including renin-angiotensin system blockers. The combination of valsartan with sacubitril also lowers BP in the short term and has demonstrated a striking reduction in CVD mortality and morbidity in HF patients with a reduced left ventricular ejection fraction. If widely adopted, these novel therapeutic agents hold significant promise for reducing the public health burden posed by HTN and CVD. Based on the results of several clinical trials and considering the high prevalence of HTN and T2D, these new classes of agents have emerged as powerful therapeutic tools in managing and lowering the BP of patients with diabetic kidney disease and HF.

摘要

综述目的

本综述旨在研究为治疗糖尿病肾病和心力衰竭(HF)而研发的新型药物的降压效果。我们总结了减轻高血压靶器官损害的潜在病理生理机制,并评估了这些新型药物的现有临床数据。

最新发现

基于非甾体二氢吡啶的盐皮质激素受体拮抗剂(MRAs)、血管紧张素II受体-脑啡肽酶双重抑制剂(缬沙坦与沙库巴曲)、钠-葡萄糖协同转运蛋白2抑制剂(SGLT2i)和可溶性鸟苷酸环化酶刺激剂是新型化学药物类别,它们具有独特的作用机制,已被证明对心血管(CV)疾病(CVD)、HF和2型糖尿病(T2D)有效。这些药物可单独使用或与其他抗高血压和CV药物联合使用。其中,SGLT2i和缬沙坦与沙库巴曲为降低CVD死亡率提供了新途径。SGLT2i对血压降低有轻度至中度作用,对CV和肾脏血流动力学有有利影响,并且与对照组(安慰剂或非SGLT2i治疗)相比,已显示出可显著降低主要不良CVD事件的发生率(作为单一疗法或附加疗法)。这些研究中的大多数参与者在基线时患有高血压(HTN),并正在接受包括肾素-血管紧张素系统阻滞剂在内的抗高血压治疗。缬沙坦与沙库巴曲的联合用药在短期内也可降低血压,并已证明在左心室射血分数降低的HF患者中可显著降低CVD死亡率和发病率。如果广泛应用,这些新型治疗药物有望显著减轻HTN和CVD带来的公共卫生负担。基于多项临床试验的结果,并考虑到HTN和T2D的高患病率,这些新型药物类别已成为管理和降低糖尿病肾病和HF患者血压的有力治疗工具。

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