Round Tables

Resistant hypertension: A growing issue, novel devices on the horizon

Treatment-resistant hypertension is a common clinical problem associated with higher risk for CV and renal adverse events, poor quality of life and increased health care costs. The exact prevalence is unknown, but resistant hypertension is projected to become more prevalent with the growing elderly population and rising obesity rates.

Keith C. Ferdinand, MD, addresses challenges and recent advances in the treatment of resistant hypertension.

Keith C. Ferdinand, MD, addresses challenges
and recent advances in the treatment
of resistant hypertension.

Images: Marty Perlman

The introduction of novel catheter-based devices to decrease sympathetic nervous system activity is growing. A 2013 European Society of Cardiology consensus document stated that “renal denervation can be considered as a therapeutic option in patients with resistant hypertension whose blood pressure cannot be controlled by a combination of lifestyle modification and pharmacological therapy according to current guidelines.”

Cardiology Today assembled a group of experts at the American Heart Association Scientific Sessions in November to tackle the topic of resistant hypertension (RHTN). In this round table, they discuss definitions, goals and current treatment options to expand the understanding of RHTN and ultimately improve long-term clinical management.

Editor’s note: This round table took place at AHA 2013 before the January press release from Medtronic about results from the SYMPLICITY HTN-3 trial.

Round Table Participants


Carl J. Pepine, MD

Cardiology Today Chief Medical Editor Division Director Emeritus Eminent Scholar Emeritus Professor of Medicine Division of Cardiovascular Medicine University of Florida College of Medicine

Deepak L. Bhatt, MD, MPH

Cardiology Today’s Intervention Chief Medical Editor
Cardiology Today Editorial Board member
Executive Director of Interventional Cardiovascular Programs
Brigham and Women’s Hospital Heart and Vascular Center
Professor of Medicine, Harvard Medical School
Co-principal Investigator, SYMPLICITY HTN-3 trial

Keith C. Ferdinand, MD

Clinical Cardiologist Professor of Clinical Medicine Tulane University, New Orleans Chair, National Forum for Heart Disease and Stroke Prevention

Manesh R. Patel, MD

Director of Interventional Cardiology Co-director, Resistant Hypertension Program Duke University Health System Investigator, SYMPLICITY HTN-3 trial

Elijah Saunders, MD

Cardiology Today Editorial Board member Professor of Medicine and Head of the Section of Hypertension University of Maryland School of Medicine Division of Cardiology Co-founder, International Society on Hypertension in Blacks and Association of Black Cardiologists Investigator, SYMPLICITY HTN-3 trial

Current definitions of hypertension

Carl J. Pepine, MD: To begin, let’s discuss current definitions of RHTN for our readers.

Keith C. Ferdinand, MD: RHTN has a variable definition. The JNC 7 mentions persons with a BP that is not controlled, despite three medications, at full doses, and optimally one of those drugs should be a diuretic. The 2008 AHA scientific statement, Resistant Hypertension: Diagnosis, Evaluation and Treatment, has a different definition: Persons who can be on four medications and the BP can be controlled, but it is still considered RHTN.

Manesh R. Patel, MD: I use the JNC 7 definition most. Dr. Ferdinand, how do you differentiate between resistant, refractory and uncontrolled?

Ferdinand: “Uncontrolled” is a general term used for persons without a BP less than goal, which we acknowledge is somewhat arbitrary. As an example, I use ≥140 mm Hg/90 mm Hg. Uncontrolled BP could be related to lack of adherence; use of a combination that is not pharmacologic optimal (beta-blocker with a central agonist); and/or consumption of large amounts of sodium, which overrides the benefits of renin-angiotensin-aldosterone system (RAAS) blockers. We use the JNC 7 definition or we use the AHA definition. “Refractory” usually means you’re doing everything right: adhering; controlling sodium; no white-coat hypertension; and so on. Yet BP remains uncontrolled.

Patel: It is an important distinction because as we think about therapies for RHTN and strategies and health systems to improve BP, we will likely see all of these groups. Yet there is overlap between those that are resistant that may still be refractory.

Pepine: You have touched on an important area for our readers. The AHA consensus document simply modified the decades-old definition popularized by Tarazi and Gifford in the 1970s.

Carl J. Pepine

Carl J. Pepine

However, as you note, the definition of RHTN remains operationally difficult and is variable in the literature. Also, much of this was from the pre-RAAS-blocker, statin and MI-reperfusion era. Others include “drugs of different pharmacologic classes,” and some also use “BP >130/80 mm Hg for patients with diabetes or CKD” while others specify patients treated with “[more than] three agents (including a thiazide) who had ≥1 BP measurement above target.” Acelajado and colleagues recently defined RHTN “as a BP that remained uncontrolled after ≥3 visits to a HTN clinic with a minimum 6-month follow-up”. As it was not possible to assure adherence, lack of measurement error, lack of white-coat hypertension and so on, “apparent treatment-resistant hypertension” is becoming popular to define the patient “not reaching goal BP on three drugs.”

Our readers should understand that we all want the RHTN definition to be a useful marker for high risk.

Barriers to care

Pepine: Practically speaking, it seems like these barriers have been around for ages and unless we have new tools or strategies for treatment of RHTN we will not be able to move forward.

Deepak L. Bhatt, MD, MPH: You are absolutely right. Often, advances in science move fields forward. Sort of like with pulmonary hypertension: It has been around forever, but there has been a lot of excitement and innovation because now some drugs are available that can actually make patients feel better. We are in a similar situation with RHTN. We have knowledge about what to do, but it may not be widely disseminated beyond hypertension experts. What has changed now is the potential to bring novel interventional techniques to the care of a subset of RHTN patients.

Elijah Saunders, MD: In our clinic, until we have given a trial of spironolactone on top of standard drugs including a diuretic (unless there is a contraindication), we do not call them resistant.

Pepine: Dr. Saunders, that is a good point that leads us to the pathophysiology of RHTN. Dr. Ferdinand, is the pathophysiology of RHTN different from that of “garden variety” essential hypertension?

Ferdinand: Primary hypertension for the most part is related to obesity, increased sodium, decreased potassium, increased alcohol, psychosocial stress and/or disadvantaged status. The Institute of Medicine says if we change those environmental factors we could decrease the hypertension burden.

With RHTN, the person has similar pathophysiology, but now has remodeling of the arterioles, left ventricular hypertrophy, chronic kidney disease, increased age and perhaps diabetes, and these factors superimpose on the various lifestyle factors already discussed. After 15 to 20 years, it is likely that such a person will become resistant.

Pepine: What about the central nervous system?

Ferdinand: Sympathetic stimulation is clearly a part of it, as Dr. Bhatt noted when he mentioned interventions.

Saunders: There are some patients in whom we cannot detect organ damage, LV hypertrophy, CKD and so forth, and they are also resistant. We all have these patients — you give every drug in the book, they are compliant with a diuretic, spironolactone, etc., but they do not respond. Yet, they don’t have a lot of LV hypertrophy or detectable renal damage. I suspect there may be some pathophysiology at the cellular level that we cannot measure.

Ferdinand: Do you think that sometimes you’re missing white-coat hypertension, patients who do not have true, sustained hypertension? Have you found that persons with RHTN and still have no target organ damage benefit from ambulatory BP monitoring?

Saunders: Rarely, but sometimes. They usually will have target organ damage. But I do see such patients with true RHTN. It’s a group that we need to know more about.