Commentary - A Promising Therapy for a Vexing Problem


Renal sympathetic denervation is a promising new therapy that – at least over the short term – has proved to be an effective, device-based approach to the treatment of severe resistant hypertension.

Resistant hypertension is a significant, vexing problem for the clinical community. However, the true number of individuals with resistant hypertension in the United States is probably higher than the recent NHANES (National Health and Nutrition Examination Survey) data reporting that more than 9 million (28%) of the roughly 33 million uncontrolled hypertensives had apparent treatment-resistant hypertension, defined as having a blood pressure greater than 140/90 mm Hg despite taking at least three antihypertensive medications of different classes (Circulation 2011;124:1046-58).

Our contemporary experience in referral hypertension clinics suggests that this estimate may be a tip of the iceberg, as some patients treated with one to two distinct antihypertensive drug classes will ultimately meet diagnostic criteria for apparent treatment-resistant hypertension after intensification of their antihypertensive drug therapy.

Resistant hypertension is important for several reasons.

First, despite the availability of more than 100 Food and Drug Administration–approved antihypertensive drugs, only one-half of all hypertensives have attained control of blood pressure to below target levels. Inadequate BP control leaves these patients at an avoidably high risk for pressure-related complications such as stroke, heart failure, retinopathy, and possibly chronic kidney disease and end-stage renal disease.

Second, the more antihypertensive drugs a patient is prescribed, the greater the likelihood of therapeutic noncompliance; the diagnosis of resistant hypertension requires prescription of at least three antihypertensive drugs. Polypharmacy in resistant hypertension increases the risk of drug-specific and/or dose-related side effects, and adds to the complexity of the antihypertensive regimen, all of which increase the likelihood of therapeutic noncompliance.

Finally, although lifestyle modifications such as dietary sodium restriction, weight loss, aerobic activity, and moderation of alcohol intake, alone or in combination, effectively lower BP, these interventions are mostly adjunctive therapy to pharmacologic therapies during hypertension treatment.

Thus, there is a compelling unmet need for therapeutic advances leading to the availability of novel, effective, safe, well tolerated, and well accepted antihypertensive therapeutic strategies.

Renal sympathetic denervation is a very promising therapy that merits more rigorous evaluation over the long term to more precisely estimate the durability of its blood pressure–lowering efficacy and safety. The current intervention strategy with Medtronic’s Symplicity catheter system is a one-time radiofrequency ablation of renal sympathetic nerves. Very importantly, the reduction in renal sympathetic nerve traffic of about 50%, although significant, is only partial.

Several aspects of this intervention, as currently performed, are attractive. The intervention depends on the cannulation and insertion of the specialized catheter into the renal arteries. In contemporary clinical practice, renal artery catheterization is performed routinely by a range of operators.

In addition, the intervention, as far as is known today, needs to be performed only once. Also, there is no internal hardware left inside the patient. Importantly, the observed BP lowering does not appear to be dependent on any specific type of antihypertensive drug therapy. Finally, this therapy does not depend on long-term adherence to daily drug therapy, which arguably increases its value to patients unwilling to adhere to medication consistently over the long term.

SYMPLICITY HTN-3 is a pivotal randomized, placebo-controlled trial for the Symplicity catheter system that will enroll over 530 patients with resistant hypertension and a systolic BP greater than 160 mm Hg despite full doses of three different antihypertensive drugs, one of which must be a diuretic. The BP-lowering efficacy will be more precisely quantified because approximately one-third of randomized participants will be in a sham intervention (placebo) group and – for the first time, longitudinal blood pressure changes will be assessed in a blinded fashion. Also, it is a 2:1 study, meaning two thirds of those randomized will receive renal artery radiofrequency ablation, providing a relatively large sample of treated individuals to be closely observed for an extended period of time.

The emergence of device-based strategies for the control of severe resistant hypertension represents a potentially landmark advance in hypertension therapeutics. Although device-based therapies are unlikely to fully supplant pharmacologic approaches, they do appear to work well with existing drug therapies to lower blood pressure, and may even lower oral medication requirements needed to control blood pressure.

These are exciting times in the field of hypertension therapeutics.

Dr. John M. Flack is professor of medicine and physiology, chairman of the department of internal medicine at Wayne State University, Detroit, and a member of the Cardiology News Editorial Advisory Board. He consults for Medtronic as a member of the SYMPLICITY HTN-3 trial steering committee, and has received grants and research support from and/or has been a consultant for other companies including Merck, Novartis, Pfizer, GlaxoSmithKline, AstraZeneca, Mannheim, Bristol-Myers Squibb, and Backbeat Medical.

Recommended Reading

IOM Calls for Research on E-Cigs, Tobacco Lozenges
MDedge Cardiology
Prior Hypertension Treatment Raises Long-Term Life Expectancy
MDedge Cardiology
Diet May Reverse 30 Years of Blood Pressure Aging
MDedge Cardiology
Excitement builds for renal denervation in hypertension
MDedge Cardiology
Blood Pressure Differences Between Arms Flags Vascular Disease
MDedge Cardiology