Renal Denervation Safe, Effective for Moderate Resistant Hypertension in Pilot Study

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Catheter-based renal denervation substantially reduces moderate treatment-resistant hypertension, achieving the therapeutic target of blood pressure (BP) below 140/90 mm Hg in about half of patients. Results of a small pilot study, published online July 10, 2013, ahead of print in the Journal of the American College of Cardiology, suggest an expanded role for the innovative therapy, which has shown efficacy against severe drug-resistant hypertension in multiple trials. 

The findings were first presented at the American College of Cardiology (ACC)/i2 Scientific Session in San Francisco, CA, in March 2013. 

For the prospective, multicenter trial, investigators led by Roland E. Schmieder, MD, of the University of Erlangen-Nuremberg (Erlangen, Germany), performed renal denervation in 54 patients with a mean office BP of 151/83 mm Hg at baseline. Patients were treated with an average of 5.1 ± 1.4 antihypertensive drugs, although 3 individuals were not receiving a diuretic due to contraindications or intolerance. Baseline 24-hour ambulatory BP monitoring demonstrated readings of 130/80 mm Hg or higher. Radiofrequency ablation was delivered via the Symplicity Catheter System (Medtronic, Mountain View, CA). 

No severe adverse events associated with the procedure were observed.

Half Met Target for BP Control

At 6 months, BP was reduced by a mean 13/7 mm Hg, with mean systolic pressure declining to 138 ± 21 mm Hg and diastolic pressure to 75 ± 11 mm Hg (P < 0.001 for both changes). Office BP was considered controlled (< 140/90 mm Hg) in just over half of patients (51%), while 61% experienced a ‘treatment response,’ defined as a systolic reduction of 10 mm Hg or more.

In the subgroup of 36 patients who had ambulatory BP monitoring both before and after denervation, 6-month ambulatory BP was decreased by 14/7 mm Hg (P <0.001 for both systolic and diastolic declines).  

In addition, heart rate was reduced by 4 beats per minute (from 67 ± 11 to 63 ± 10 ; P = 0.006).  The change in heart rate did not correlate with the reduction in systolic BP, suggesting that the heart rate change is independent of the intervention’s BP lowering effects.

Despite protocol recommendation to the contrary, 37% of patients curtailed their antihypertensive regimen during 6-month follow-up. Interestingly, in an exploratory analysis, reductions in systolic pressure (13 mm Hg) were identical between those who did and did not maintain their original regimen, while the decline in diastolic pressure was actually larger in patients who altered their medications (9 mm Hg vs. 6 mm Hg).

Modest BP Declines Clinically Relevant

The office BP reduction in the current study is considerably smaller than that reported in trials of severe hypertension, the authors acknowledge, which is not surprising since “pretreatment BP is the major determinant of the magnitude of BP fall.” Nonetheless, they note, many studies have shown that “even modest BP reductions are accompanied by significant attenuation of CV morbidity and mortality.”

In a telephone interview with TCTMD, Deepak L. Bhatt, MD, MPH, of Brigham and Women’s Hospital (Boston, MA), said that while the case for denervation is now fairly compelling among patients with severe hypertension--especially if they are experiencing medication side effects--for those with moderate hypertension on a well-tolerated antihypertensive regimen, the decision must take into account potential complications and the cost of an invasive procedure.

David E. Kandzari, MD, of the Piedmont Heart Institute (Atlanta, GA), agreed. “This is the next logical transition in treating the entire space of medication-resistant hypertension,” he told TCTMD in a telephone interview, commenting that the threshold of 160/90 mm Hg for participation in the original trials was somewhat arbitrary. On the other hand, he said, in Europe and elsewhere outside the United States, practitioners are already offering denervation to patients whose modest hypertension would make them ineligible for clinical trials, and neither the current study nor a recent small series with similar results (Kaltenbach B, et al. Catheter Cardiovasc Interv. 2013; 81:335-339) is a substitute for such trials.

“We need a large population to demonstrate the safety of the procedure because it has a small but measurable risk, which is particularly relevant to patients with moderate hypertension who might have a different risk-benefit ratio than patients with a systolic BP of 200 mm Hg,” Dr. Kandzari said.

Next Up: Symplicity HTN-4

In an accompanying editorial, Krishna J. Rocha-Singh, MD, and Richard E. Katholi, MD, both of Prairie Vascular Institute (Springfield, IL), say the pilot study sets the stage for the upcoming randomized Symplicity HTN-4 trial in the same population. 

Noting the high rate of so-called nonresponders, the editorial argues that the concept should be redefined in future research. Dr. Kandzari agreed, calling the 10-point threshold for ‘response’ questionable in patients whose baseline BP was only moderately elevated. Moreover, the editorial points out, in longer-term follow-up of the Symplicity HTN-1 and 2 trials, many ‘nonresponders’ turned out to be merely ‘slow responders.’ Thus, they say, a 6-month BP reduction may not be the maximum that will be achieved.

Dr. Bhatt concurred that the physiological response to denervation may be delayed. But in other cases, he said, ‘nonresponse’ may be due to limitations of the current ablation catheters or to suboptimal operator technique. Alternatively, in some patients hypertension may be caused by additional, nonsympathetic mechanisms, he added.

Are Drugs Still Needed?

Drs. Rocha-Singh and Katholi say an important unresolved issue is whether patients who have undergone renal denervation need to maintain a full antihypertensive regimen over the long term.

Dr. Kandzari observed that in previous trials the proportion of patients who have been able to reduce the dose or number of antihypertensive drugs has ranged from 15% to 25%, while about 10% to 15% have had to increase their regimen. “In this study, the percentage of patients who reduced their medication burden was much higher,” he said. “But across registries, we’ve seen that when patients and physicians know what treatment has been received, management of antihypertensive medications tends to be different from what it is in trials.”

Nonetheless, if a significant proportion of patients can achieve the Joint National Committee goal of a systolic BP below 140 mm Hg on a reduced regimen, “that will not only be very clinically relevant but it may also influence reimbursement for renal denervation,” Dr. Kandzari noted. It would also likely mean the therapy will be cost-effective in moderate hypertension, he added.

Dr. Bhatt added that reducing medications would have the advantage of fewer side effects. But he cautioned that stopping antihypertensive drugs could be counterproductive if they were also serving other cardiovascular purposes, as is often the case with beta blockers and ACE inhibitors.


1. Ott C, Mahfoud F, Schmid A, et al. Renal denervation in moderate treatment resistant hypertension. J Am Coll Cardiol. 2013;Epub ahead of print.

2. Rocha-Singh KJ, Katholi RE. Renal sympathetic denervation for treatment resistant hypertension…in moderation. J Am Coll Cardiol. 2013;Epub ahead of print.



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Renal Denervation Safe, Effective for Moderate Resistant Hypertension in Pilot Study

Catheter based renal denervation substantially reduces moderate treatment resistant hypertension, achieving the therapeutic target of blood pressure (BP) below 140 90 mm Hg in about half of patients. Results of a small pilot study, published online July 10, 2013, ahead of
  • Dr. Schmieder reports receiving research funding from and serving as a consultant to Medtronic.
  • Dr. Rocha-Singh reports serving as a consultant or adviser to Boston Scientific, Cardiosonic, and Medtronic.
  • Dr. Katholi reports serving as a consultant to and investigator for Medtronic.
  • Dr. Bhatt reports receiving research grants from Amarin, AstraZeneca, Bristol-Myers Squibb, Eisai, Ethicon, Medtronic, Sanofi-Aventis, and The Medicines Company, and serving as co-principal investigator for the Symplicity HTN-3 trial.
  • Dr. Kandzari reports receiving research and grant support as well as honoraria for consultation from Medtronic. He is also co-principal investigator for the Symplicity HTN-4 trial.