June 17, 2013

MILAN, Italy — A study of the benefits of renal denervation for the treatment of resistant hypertension suggests that the reduction in blood pressure is smaller than observed in clinical trials and is considerably smaller when systolic blood pressure is assessed using ambulatory blood-pressure monitoring (ABPM).

In fact, when ABPM was used to measure blood pressure, the reduction was just one-third of that observed when assessed in the office. On average, the reduction in blood pressure when using traditional office-cuff measurements was 17.6 mm Hg six months after renal denervation, but the reduction was just 5.9 mm Hg when assessed using 24-hour ABPM.

Speaking with heartwire , lead investigator Prof Alexandre Persu (Cliniques Universitaires Saint-Luc, Brussels, Belgium) said that in drug studies, 60% to 70% of the office reduction is retained on ABPM, so the smaller decrease observed with renal denervation is highly unusual.

"Our results on the office measurement are less than what was observed in the SYMPLICITY HTN-2 trial but still in the same range," said Persu. "But in SYMPLICITY, there are only few ABPM results, and even in those that were done, the reduction was also just one-third [of the office measurements]. Our study is the largest collection of ambulatory blood-pressure measurements, and the results on ABPM are not impressive. That's why we are skeptical. We are not sure if this modest reduction would translate into a reduction into hard clinical events. It's possible, but it still remains to be proven."

ABPM Reduction Not as Impressive

The new data, presented here this week at the European Society of Hypertension (ESH) 2013 Scientific Sessions , is derived from a collaboration of 10 large European hypertension clinics within the European Network Coordinating Research on Renal Denervation (ENCORED), initiated by Prof Jan Staessen (University of Leuven, Belgium). In total, 109 patients with resistant hypertension were treated with renal denervation at hypertension clinics in Belgium, France, the Czech Republic, Norway, the UK, Switzerland, and Sweden.

The results on ABPM are not impressive.

The baseline office systolic blood pressure was 175 mm Hg, and the baseline 24-hour ambulatory blood pressure was 157 mm Hg. At six months, office and ABPM systolic blood pressure were reduced by 17.6 mm Hg and 5.9 mm Hg, respectively (p<0.03 for both).

As a comparison, Persu cited the Syst-Eur trial, a placebo-controlled study of elderly patients with isolated systolic hypertension, another difficult-to-control form of hypertension. The 24-hour ABPM reduction in systolic blood pressure achieved with renal denervation at the 10 clinical centers was just 3.9 mm Hg larger than what was observed in placebo-treated patients in Syst-Eur, said Persu.

"We think that renal denervation should be mainly for research right now," said Persu. "It should be reserved only as a last resort for truly resistant hypertensive patients in whom all attempts have been made to lower blood pressure at expert clinical centers."

Large Variation in Response to Treatment

The analysis also revealed a very large variation in the response to renal denervation. In fact, a substantial proportion of patients treated with renal denervation had no change in blood pressure at all or even showed increased systolic blood pressure after the procedure. When measured in the office, 23% of patients who received renal denervation had unchanged or higher blood pressure six months after the procedure. Using ABPM, this proportion increased to 35%, while the results were much more consistent in the active treatment arm of Syst-Eur.

"As a whole, our results suggest an important contribution of placebo or Hawthorne effects and/or regression to the mean in the observed response to renal denervation," Persu told heartwire . "There might be true responders, and we have observed important reductions in blood pressure in a limited number of patients, but we can't predict who these patients are going to be, and, in fact, we do not know what really happened in these specific cases. If this technique is going to make it in clinical practice, we definitely need to identify factors that are predictive of treatment success."

Future steps, according to Persu, are randomized, controlled clinical trials that include a primary end point using ABPM. In addition, drug therapy needs to be optimized and patients need to be screened appropriately for secondary and white-coat resistant hypertension, including only those with truly resistant hypertension. In the real world, the prevalence of apparently resistant hypertension is approximately 10% to 15%, according to Persu, but the proportion is significantly reduced when ABPM is used to assess blood pressure, and the proportion of patients who will finally prove eligible for renal denervation is even lower.

"We have found that the results of renal denervation are highly variable in real life, and we wanted to try to have an unbiased look at the procedure and the results achieved in hypertension centers," Persu said. "The final word will come from the new randomized, controlled clinical trials."

New guidelines for the management of hypertension were presented at the ESH meeting this week, and while the writing committee, comprising ESH and European Society of Cardiology (ESC) experts, called renal denervation promising, the group stopped there. The guidelines state that the procedure needs more data from long-term comparison trials to establish safety and efficacy against the best possible drug regimens.


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.