Bharathi Upadhya1, Patrick M Kozak2, Richard Brandon Stacey2, Ramachandran S Vasan3. 1. Cardiovascular Medicine Section, Department of Internal Medicine, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC, 27157-1045, USA. bupadhya@wakehealth.edu. 2. Cardiovascular Medicine Section, Department of Internal Medicine, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC, 27157-1045, USA. 3. 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.
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.
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.
Authors: Bryan Williams; Thomas M MacDonald; Steve Morant; David J Webb; Peter Sever; Gordon McInnes; Ian Ford; J Kennedy Cruickshank; Mark J Caulfield; Jackie Salsbury; Isla Mackenzie; Sandosh Padmanabhan; Morris J Brown Journal: Lancet Date: 2015-09-20 Impact factor: 79.321
Authors: Sandra Feijóo-Bandín; Alana Aragón-Herrera; Manuel Otero-Santiago; Laura Anido-Varela; Sandra Moraña-Fernández; Estefanía Tarazón; Esther Roselló-Lletí; Manuel Portolés; Oreste Gualillo; José Ramón González-Juanatey; Francisca Lago Journal: Int J Mol Sci Date: 2022-05-18 Impact factor: 6.208