4.5 Review

Novel antihypertensive agents for resistant hypertension: what does the future hold?

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Review Pharmacology & Pharmacy

Novel non-steroidal mineralocorticoid receptor antagonists in cardiorenal disease

Ulrich Kintscher et al.

Summary: This review provides information on the molecular pharmacology and relevant clinical data of a new class of non-steroidal MRAs, discussing their cardiorenal outcomes. These compounds have an improved benefit-risk profile in treating cardiovascular diseases, and finerenone has a novel indication.

BRITISH JOURNAL OF PHARMACOLOGY (2022)

Review Pharmacology & Pharmacy

The mineralocorticoid receptor in chronic kidney disease

Jonatan Barrera-Chimal et al.

Summary: Chronic kidney disease is a major public health concern globally, with MR antagonists emerging as a potential therapeutic approach against various forms of kidney disease. Experimental and clinical studies have shown the protective effects of MRAs in reducing albuminuria and slowing disease progression. Recent evidence also suggests that MRAs can reduce hard kidney outcomes, particularly in CKD associated with type 2 diabetes, highlighting their potential benefit in maximizing organ protection through combination therapy.

BRITISH JOURNAL OF PHARMACOLOGY (2022)

Article Pharmacology & Pharmacy

Effects of the Dual Endothelin Receptor Antagonist Aprocitentan on Body Weight and Fluid Homeostasis in Healthy Subjects on a High Sodium Diet

Pierre Gueneau de Mussy et al.

Summary: Aprocitentan, a novel dual endothelin receptor antagonist in development for difficult-to-control hypertension, was found to cause moderate weight gain in healthy subjects on a high sodium diet without obvious sodium retention.

CLINICAL PHARMACOLOGY & THERAPEUTICS (2021)

Review Cardiac & Cardiovascular Systems

Aprocitentan, A Dual Endothelin Receptor Antagonist Under Development for the Treatment of Resistant Hypertension

Fabio Angeli et al.

Summary: Aprocitentan is an orally active dual endothelin-1 receptor antagonist with good tolerability and a long half-life. It may have antihypertensive and cardiovascular protective effects in patients with resistant hypertension.

CARDIOLOGY AND THERAPY (2021)

Article Pharmacology & Pharmacy

An evaluation of KBP-5074 in advanced chronic kidney disease with uncontrolled hypertension

Bertram Pitt et al.

Summary: This study reviews the current challenges in treating RH in CKD patients and the potential application of a novel nonsteroidal MRA (KBP-5074) in this area.

EXPERT OPINION ON INVESTIGATIONAL DRUGS (2021)

Article Pharmacology & Pharmacy

Differentiation between emerging non-steroidal and established steroidal mineralocorticoid receptor antagonists: head-to-head comparisons of pharmacological and clinical characteristics

Jonatan Barrera-Chimal et al.

Summary: The new non-steroidal MRAs may have at least equivalent efficacy to steroidal MRAs but potentially offer a better safety profile in patients with heart failure and/or kidney disease. Further research is needed to understand the molecular differences in their mode of action and identify predictive biomarkers for MRA response.

EXPERT OPINION ON INVESTIGATIONAL DRUGS (2021)

Review Pharmacology & Pharmacy

Aldosterone synthase inhibitors for cardiovascular diseases: A comprehensive review of preclinical, clinical and in silico data

Livia Lenzini et al.

Summary: Aldosterone, a crucial hormone for blood pressure and volume regulation, can become harmful when overproduced in certain diseases. Inhibiting aldosterone synthase, the enzyme responsible for aldosterone biosynthesis, has shown promise in controlling aldosterone excess. Several aldosterone synthase inhibitors have shown hopeful results in clinical trials.

PHARMACOLOGICAL RESEARCH (2021)

Article Cardiac & Cardiovascular Systems

Pathophysiology of Hypertension The Mosaic Theory and Beyond

David G. Harrison et al.

Summary: Dr. Irvine Page proposed the Mosaic Theory of Hypertension in the 1940s, advocating that hypertension is the result of many interacting factors. Over the years, new concepts have arisen that allow further refinements of the theory, emphasizing the interdependence of various nodes.

CIRCULATION RESEARCH (2021)

Review Urology & Nephrology

Endothelin receptor antagonists for the treatment of diabetic and nondiabetic chronic kidney disease

J. David Smeijer et al.

Summary: Endothelin receptor antagonists show significant kidney protection in patients with diabetic kidney disease, with potential therapeutic effects in non-diabetic kidney diseases such as IgA nephropathy and FSGS.

CURRENT OPINION IN NEPHROLOGY AND HYPERTENSION (2021)

Article Peripheral Vascular Disease

Effect of KBP-5074 on Blood Pressure in Advanced Chronic Kidney Disease: Results of the BLOCK-CKD Study

George Bakris et al.

Summary: In patients with resistant or poorly controlled hypertension and advanced chronic kidney disease, the nonsteroidal mineralocorticoid receptor antagonist KBP-5074 effectively lowers blood pressure with some risk of hyperkalemia.

HYPERTENSION (2021)

Review Cardiac & Cardiovascular Systems

Aprocitentan (a Dual Endothelin-Receptor Antagonist) for Treatment-Resistant Hypertension

Emily K. McCoy et al.

Summary: Treatment-resistant hypertension (TRH) is associated with increased cardiovascular risks and progression of chronic kidney disease. Aprocitentan, a novel dual endothelin-receptor antagonist, has shown promising results in early clinical trials for TRH patients, demonstrating significant blood pressure reduction and improved tolerability compared to other antagonists. Ongoing phase 3 trials will further evaluate its efficacy and safety.

JOURNAL OF CARDIOVASCULAR PHARMACOLOGY (2021)

Editorial Material Cardiac & Cardiovascular Systems

Sacubitril/valsartan for heart failure with preserved ejection fraction and resistant hypertension: one shot for a double strike?

Massimo Volpe et al.

EUROPEAN HEART JOURNAL (2021)

Article Cardiac & Cardiovascular Systems

Sacubitril-valsartan as a treatment for apparent resistant hypertension in patients with heart failure and preserved ejection fraction

Alice M. Jackson et al.

Summary: The study showed that sacubitril-valsartan may be effective in treating apparent resistant hypertension in patients with HFpEF, even in those who continue to have elevated blood pressure despite treatment with at least four antihypertensive drug classes, including an MRA.

EUROPEAN HEART JOURNAL (2021)

Article Pharmacology & Pharmacy

The Non-Steroidal Mineralocorticoid Receptor Antagonist KBP-5074 Limits Albuminuria and has Improved Therapeutic Index Compared With Eplerenone in a Rat Model With Mineralocorticoid-Induced Renal Injury

Frederic Jaisser et al.

Summary: KBP-5074 demonstrated higher efficacy and broader therapeutic window compared with eplerenone in treating kidney disease, suggesting a promising non-steroidal mineralocorticoid receptor antagonist for preventing aldosterone-induced renal injury.

FRONTIERS IN PHARMACOLOGY (2021)

Article Cardiac & Cardiovascular Systems

Antisense Inhibition of Angiotensinogen With IONIS-AGT-LRx

Erin S. Morgan et al.

Summary: Targeting angiotensinogen (AGT) with IONIS-AGT-L-Rx significantly reduces AGT levels and demonstrates favorable safety and tolerability in clinical trials. Potential blood pressure reduction effects were observed, although not specifically studied for this endpoint.

JACC-BASIC TO TRANSLATIONAL SCIENCE (2021)

Review Urology & Nephrology

Targeting angiotensinogen with RNA-based therapeutics

Liwei Ren et al.

CURRENT OPINION IN NEPHROLOGY AND HYPERTENSION (2020)

Review Biotechnology & Applied Microbiology

The current state and future directions of RNAi-based therapeutics

Ryan L. Setten et al.

NATURE REVIEWS DRUG DISCOVERY (2019)

Review Medicine, General & Internal

Treating Disease at the RNA Level with Oligonucleotides

Arthur A. Levin

NEW ENGLAND JOURNAL OF MEDICINE (2019)

Article Cardiac & Cardiovascular Systems

Anti-Hypertensive Effect of Sacubitril/Valsartan: A Meta-Analysis of Randomized Controlled Trials

Renato De Vecchis et al.

CARDIOLOGY RESEARCH (2019)

Review Peripheral Vascular Disease

Update on Endothelin Receptor Antagonists in Hypertension

Michel Burnier

CURRENT HYPERTENSION REPORTS (2018)

Editorial Material Peripheral Vascular Disease

Benefits and pitfalls of sacubitril/valsartan treatment in patients with hypertension

Steven G. Chrysant

JOURNAL OF CLINICAL HYPERTENSION (2018)

Review Biochemistry & Molecular Biology

GalNAc-siRNA Conjugates: Leading the Way for Delivery of RNAi Therapeutics

Aaron D. Springer et al.

NUCLEIC ACID THERAPEUTICS (2018)

Article Medicine, General & Internal

Hypertension

Suzanne Oparil et al.

NATURE REVIEWS DISEASE PRIMERS (2018)

Review Cardiac & Cardiovascular Systems

2018 ESC/ESH Guidelines for the management of arterial hypertension

Bryan Williams et al.

EUROPEAN HEART JOURNAL (2018)

Editorial Material Cardiac & Cardiovascular Systems

Advantages of sacubitril/valsartan beyond blood pressure control in arterial hypertension

Gema Ruiz-Hurtado et al.

EUROPEAN HEART JOURNAL (2017)

Article Cardiac & Cardiovascular Systems

The Effects of LCZ696 in Patients With Hypertension Compared With Angiotensin Receptor Blockers: A Meta-Analysis of Randomized Controlled Trials

Yang Zhao et al.

JOURNAL OF CARDIOVASCULAR PHARMACOLOGY AND THERAPEUTICS (2017)

Review Urology & Nephrology

Endothelin A receptor antagonists in diabetic kidney disease

Panagiotis I. Georgianos et al.

CURRENT OPINION IN NEPHROLOGY AND HYPERTENSION (2017)

Review Peripheral Vascular Disease

DOCA-Salt Hypertension: an Update

Tyler Basting et al.

CURRENT HYPERTENSION REPORTS (2017)

Article Medicine, General & Internal

Time-Updated Systolic Blood Pressure and the Progression of Chronic Kidney Disease A Cohort Study

Amanda H. Anderson et al.

ANNALS OF INTERNAL MEDICINE (2015)

Review Cardiac & Cardiovascular Systems

Role of neprilysin inhibitor combinations in hypertension: insights from hypertension and heart failure trials

Chirag Bavishi et al.

EUROPEAN HEART JOURNAL (2015)

Editorial Material Peripheral Vascular Disease

Interpretation of ambulatory blood pressure profile: a prognostic approach for clinical practice

Fabio Angeli et al.

JOURNAL OF HYPERTENSION (2015)

Article Medicine, General & Internal

Angiotensin-Neprilysin Inhibition versus Enalapril in Heart Failure

John J. V. McMurray et al.

NEW ENGLAND JOURNAL OF MEDICINE (2014)

Review Urology & Nephrology

Prediction and Management of Hyperkalemia Across the Spectrum of Chronic Kidney Disease

Lvana Lazich et al.

SEMINARS IN NEPHROLOGY (2014)

Article Peripheral Vascular Disease

Dual-Acting Angiotensin Receptor-Neprilysin Inhibition

Julian Segura et al.

CURRENT HYPERTENSION REPORTS (2011)

Article Peripheral Vascular Disease

Combination Therapy in Hypertension

Alan H. Gradman et al.

JOURNAL OF CLINICAL HYPERTENSION (2011)

Review Medicine, Research & Experimental

At the heart of tissue: endothelin system and end-organ damage

Marc Iglarz et al.

CLINICAL SCIENCE (2010)

Article Urology & Nephrology

Avosentan for Overt Diabetic Nephropathy

Johannes F. E. Mann et al.

JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY (2010)

Editorial Material Cardiac & Cardiovascular Systems

Hypertension and the J-Curve

Bryan Williams

JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY (2009)

Review Peripheral Vascular Disease

Role of endothelin-1 in clinical hypertension - 20 years on

Neeraj Dhaun et al.

HYPERTENSION (2008)

Article Medicine, General & Internal

Benazepril plus Amlodipine or Hydrochlorothiazide for Hypertension in High-Risk Patients

Kenneth Jamerson et al.

NEW ENGLAND JOURNAL OF MEDICINE (2008)

Review Peripheral Vascular Disease

The burden of blood pressure-related disease - A neglected priority for global health

Vlado Perkovic et al.

HYPERTENSION (2007)

Review Peripheral Vascular Disease

Salt sensitivity of Japanese from the viewpoint of gene polymorphism

T Katsuya et al.

HYPERTENSION RESEARCH (2003)

Article Medicine, General & Internal

Value of low dose combination treatment with blood pressure lowering drugs: analysis of 354 randomised trials

MR Law et al.

BMJ-BRITISH MEDICAL JOURNAL (2003)

Article Medicine, General & Internal

Effect of blood pressure lowering and antihypertensive drug class on progression of hypertensive kidney disease - Results from the AASK trial

JT Wright et al.

JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION (2002)

Article Biochemistry & Molecular Biology

Comparison of antisense oligonucleotides and siRNAs in cell culture and in vivo

JR Bertrand et al.

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS (2002)

Article Medicine, General & Internal

Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy

BM Brenner et al.

NEW ENGLAND JOURNAL OF MEDICINE (2001)

Article Multidisciplinary Sciences

Metabolic regulation of brain Aβ by neprilysin

N Iwata et al.

SCIENCE (2001)