New approaches in the treatment of hypertension

Circ Res. 2015 Mar 13;116(6):1074-95. doi: 10.1161/CIRCRESAHA.116.303603.

Abstract

Hypertension is the most common modifiable risk factor for cardiovascular disease and death, and lowering blood pressure with antihypertensive drugs reduces target organ damage and prevents cardiovascular disease outcomes. Despite a plethora of available treatment options, a substantial portion of the hypertensive population has uncontrolled blood pressure. The unmet need of controlling blood pressure in this population may be addressed, in part, by developing new drugs and devices/procedures to treat hypertension and its comorbidities. In this Compendium Review, we discuss new drugs and interventional treatments that are undergoing preclinical or clinical testing for hypertension treatment. New drug classes, eg, inhibitors of vasopeptidases, aldosterone synthase and soluble epoxide hydrolase, agonists of natriuretic peptide A and vasoactive intestinal peptide receptor 2, and a novel mineralocorticoid receptor antagonist are in phase II/III of development, while inhibitors of aminopeptidase A, dopamine β-hydroxylase, and the intestinal Na(+)/H(+) exchanger 3, agonists of components of the angiotensin-converting enzyme 2/angiotensin(1-7)/Mas receptor axis and vaccines directed toward angiotensin II and its type 1 receptor are in phase I or preclinical development. The two main interventional approaches, transcatheter renal denervation and baroreflex activation therapy, are used in clinical practice for severe treatment resistant hypertension in some countries. Renal denervation is also being evaluated for treatment of various comorbidities, eg, chronic heart failure, cardiac arrhythmias and chronic renal failure. Novel interventional approaches in early development include carotid body ablation and arteriovenous fistula placement. Importantly, none of these novel drug or device treatments has been shown to prevent cardiovascular disease outcomes or death in hypertensive patients.

Keywords: blood pressure; drug; hypertension; interventional; treatment.

Publication types

  • Review

MeSH terms

  • Animals
  • Antihypertensive Agents / pharmacology
  • Antihypertensive Agents / therapeutic use*
  • Arteriovenous Shunt, Surgical
  • Baroreflex / physiology
  • Carotid Body / surgery
  • Clinical Trials as Topic
  • Comorbidity
  • Decompression, Surgical
  • Drug Design
  • Drugs, Investigational / pharmacology
  • Drugs, Investigational / therapeutic use*
  • Electric Stimulation Therapy
  • Enzyme Inhibitors / pharmacology
  • Enzyme Inhibitors / therapeutic use
  • Female
  • High-Intensity Focused Ultrasound Ablation
  • Humans
  • Hypertension / drug therapy
  • Hypertension / enzymology
  • Hypertension / pathology
  • Hypertension / therapy*
  • Ion Channels / drug effects
  • Kidney / innervation
  • Kidney Tubules / drug effects
  • Kidney Tubules / physiopathology
  • Mineralocorticoid Receptor Antagonists / pharmacology
  • Mineralocorticoid Receptor Antagonists / therapeutic use
  • Models, Animal
  • Molecular Targeted Therapy
  • Multicenter Studies as Topic
  • Oxidative Stress / drug effects
  • Pre-Eclampsia / drug therapy
  • Pre-Eclampsia / prevention & control
  • Pregnancy
  • Pressoreceptors / physiology
  • Randomized Controlled Trials as Topic
  • Receptors, Cell Surface / antagonists & inhibitors
  • Renal Artery / surgery
  • Renin-Angiotensin System / drug effects
  • Renin-Angiotensin System / physiology
  • Stents
  • Sympathectomy / methods
  • Sympathetic Nervous System / drug effects
  • Sympathetic Nervous System / physiopathology
  • Therapies, Investigational*

Substances

  • Antihypertensive Agents
  • Drugs, Investigational
  • Enzyme Inhibitors
  • Ion Channels
  • Mineralocorticoid Receptor Antagonists
  • Receptors, Cell Surface