NYMC Faculty Publications

Drug Therapy of Apparent Treatment-Resistant Hypertension: Focus on Mineralocorticoid Receptor Antagonists

Author Type(s)

Faculty

DOI

10.1007/s40265-015-0372-3

Journal Title

Drugs

First Page

473

Last Page

485

Document Type

Article

Publication Date

4-1-2015

Department

Pharmacology

Second Department

Medicine

Keywords

Angiotensin Receptor Antagonists, Angiotensin-Converting Enzyme Inhibitors, Animals, Antihypertensive Agents, Calcium Channel Blockers, Comorbidity, Diuretics, Drug Monitoring, Drug Resistance, Multiple, Drug Therapy, Combination, Evidence-Based Medicine, Humans, Hypertension, Mineralocorticoid Receptor Antagonists, Practice Guidelines as Topic

Disciplines

Medicine and Health Sciences

Abstract

Apparent treatment-resistant hypertension (aTRH) is defined as blood pressure (BP) >140/90 mmHg despite three different antihypertensive drugs including a diuretic. aTRH is associated with an increased risk of cardiovascular events, including stroke, chronic renal failure, myocardial infarction, congestive heart failure, aortic aneurysm, atrial fibrillation, and sudden death. Preliminary studies of renal nerve ablation as a therapy to control aTRH were encouraging. However, these results were not confirmed by the Symplicity 3 trial. Therefore, attention has refocused on drug therapy. Secondary forms of hypertension and associated conditions such as obesity, sleep apnea, and primary aldosteronism are common in patients with aTRH. The pivotal role of aldosterone in the pathogenesis of aTRH in many cases is well recognized. For patients with aTRH, the Joint National Committee-8, the European Society of Hypertension, and a recent consensus conference recommend that a diuretic, ACE inhibitor, or angiotensin receptor blocker and calcium channel blocker combination be used to maximally tolerated doses before starting a 'fourth-line' drug such as a mineralocorticoid receptor (MR) antagonist. Although the best fourth-line drug for aTRH has not been extensively investigated, a number of studies summarized here show that an MR antagonist is effective in reducing BP when added to the standard multi-drug regimen.

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