- Ernesto L Schiffrin, distinguished James McGill professor of medicine1,
- Naomi D L Fisher, associate professor of medicine2
1Lady Davis Institute for Medical Research and Department of Medicine, Sir Mortimer B. Davis-Jewish General Hospital, McGill University, Montréal, QC, Canada
2Department of Medicine, Brigham and Women’s Hospital, Harvard University, Boston, MA, USA
- Correspondence to: E L Schiffrin ernesto.schiffrin{at}mcgill.ca
Abstract
Resistant hypertension is defined as blood pressure that remains above the therapeutic goal despite concurrent use of at least three antihypertensive agents of different classes, including a diuretic, with all agents administered at maximum or maximally tolerated doses. Resistant hypertension is also diagnosed if blood pressure control requires four or more antihypertensive drugs. Assessment requires the exclusion of apparent treatment resistant hypertension, which is most often the result of non-adherence to treatment. Resistant hypertension is associated with major cardiovascular events in the short and long term, including heart failure, ischemic heart disease, stroke, and renal failure. Guidelines from several professional organizations recommend lifestyle modification and antihypertensive drugs. Medications typically include an angiotensin converting enzyme inhibitor or angiotensin receptor blocker, a calcium channel blocker, and a long acting thiazide-type/like diuretic; if a fourth drug is needed, evidence supports addition of a mineralocorticoid receptor antagonist. After a long pause since 2007 when the last antihypertensive class was approved, several novel agents are now under active development. Some of these may provide potent blood pressure lowering in broad groups of patients, such as aldosterone synthase inhibitors and dual endothelin receptor antagonists, whereas others may provide benefit by allowing treatment of resistant hypertension in special populations, such as non-steroidal mineralocorticoid receptor antagonists in patients with chronic kidney disease. Several device based approaches have been tested, with renal denervation being the best supported and only approved interventional device treatment for resistant hypertension.
Footnotes
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Series explanation: State of the Art Reviews are commissioned on the basis of their relevance to academics and specialists in the US and internationally. For this reason they are written predominantly by US authors
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Contributors: Both authors contributed to the planning, conduct, and reporting of the work described in the article, and both are responsible for the overall content as guarantors.
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Funding: The research reported from the work of ELS and the present work were supported by Canadian Institutes of Health Research (CIHR) grants 37917, First Pilot Foundation Grant 143348 and Project Grant PJT 186248, a Canada Research Chair (CRC) on Hypertension and Vascular Research by the CRC Government of Canada/CIHR Program, by the Canada Fund for Innovation, and a Distinguished James McGill Professorship.
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Competing interests: We have read and understood the BMJ policy on declaration of interests and declare the following interests: ELS has been a member of advisory boards of Janssen Pharmaceuticals USA and Boehringer Ingelheim International; NDLF was a consultant for and received research grants from Recor Medical and was a consultant for Medtronic and Astra Zeneca.
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Patient involvement: No patients were asked for input in the creation of this article.
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Provenance and peer review: Commissioned; externally peer reviewed.