CHICAGO—The first human, randomized controlled trial of sympathetic renal denervation for treatment-resistant hypertension found a significant decrease in office systolic blood pressure (SBP) after 6 months. Also, medication decreases were reported in 20% of patients undergoing renal denervation, said Murray Esler, MD, Baker IDI Heart and Diabetes Institute, Melbourne, Australia, at the American Heart Association (AHA) 2010 Scientific Sessions.
Research over the last 2 decades has confirmed that renal sympathetic afferent and efferent nerves play a seminal role in mediating hypertension (M Esler, G Lambert, G Jennings, J Hypertension 1990;8:S53-S57 [Updated]), Dr. Esler said, and furthermore, renal denervation, in many experimental forms of hypertension, delays or prevents hypertension onset (GF DiBona, Physiol Rev 1997;77:75-197).
Symplicity HTN-2 investigators enrolled 190 patients with treatment-resistant hypertension in 24 centers in Europe, Australia and New Zealand. Resistant-hypertension was defined as blood pressure that remains above goal in spite of concurrent use of 3 antihypertensive agents of different classes prescribed at optimal doses. Included patients (n=106, mean age 58 years) had office SBP ≥160 mmHg (≥150 mmHg with type 2 diabetes), were taking ≥3 anti-hypertensive medications and had a bilateral single main renal artery of >20 mm length and 4 mm diameter. They were randomized 1:1 to either catheter-based renal denervation or to control (antihypertensive medications). The primary endpoint was automated office SBP change from baseline to 6 months.
Patients randomized to active treatment in the Symplicity HTN-2 trial received 4-6 two-minute treatments with a fully automated, proprietary radiofrequency generator (Symplicity Catheter System, Ardian Inc.) and antihypertensive medications.
Baseline blood pressures were nearly identical at 178/98 mm Hg and 178/97 mm HG in the treatment + medication group and the medication only group, respectively. About three-fourths of patients had been receiving anti-hypertensive medications for >5 years. Also, ~two-thirds were taking 5 or more anti-hypertensive medications at baseline.
Analysis of the primary endpoint at 6 months showed reductions of 32 mm Hg and 12 mm Hg in systolic and diastolic blood pressures (DBPs), respectively, in the renal denervation group as compared with virtually no change in the control group (1 mm increase in SBP; 0 change in DBP, p<0.0001 for renal denervation versus controls). Home blood pressures were reduced significantly compared with baseline by 20/12 mm in the renal denvervation group. SBP increased by 2 mm Hg and DBP remained the same for controls. Twenty-four hour ambulatory blood pressures were reduced by 11/7 mm Hg (p=0.014 versus baseline) with renal denvervation as compared with 3/1 mm Hg for controls (NS versus baseline).
Dr. Esler noted that 84% of renal denervation patients had ≥10 mm Hg reduction in SBP. Furthermore, 20% of renal denervation patients reduced their medication dose as opposed to 8% of controls. Medication dose increases were reported among 8% of renal denervations patients and among 10% of controls.
Commenting that “risk to the arterial wall was very much on our mind,” Dr. Esler reported no acute procedural artery damage with minor adverse events only.
Dr. Esler concluded, “Catheter-based renal denervation in patients with treatment-resistant essential hypertension results in very substantial reductions in blood pressure.” He added, “This trial affirms the crucial relevance of renal nerves in the maintenance of elevated blood pressure.” Dr. Esler said that a US-based trial is in development, and that application of the technique in patients with less severe essential hypertension is under consideration.
AHA discussant Suzanne Oparil, MD, professor of medicine, physiology and biophysics at the University of Birmingham, Birmingham, AL, noted the strong rationale for this research: “There is a major clinical need for something more for treating resistant hypertension.” She pointed at that while there are many new combinations of drugs being explored, there have been no novel therapeutic solutions, and lifestyle modification strategies “are not so hot.” At the same time, Dr. Oparil added, the population is older and heavier with rising rates of metabolic syndrome, diabetes and chronic kidney disease—all patient groups that are difficult to treat. “It’s estimated that 15% of all hypertensive patients have a treatment-resistant form.”
Dr. Oparil called the office blood pressure reductions “excellent,” but noted the reduced benefit shown in the ambulatory monitoring studies. She found it reassuring that there were no serious device or procedure-related adverse events, and that renal function remained stable.
Listing some study limitations and a range of unanswered questions, she emphasized the small (17%) proportion of patients receiving aldosterone antagonists. “This class of agents has emerged as probably the most effective one for lowering blood pressure in patients with resistant hypertension whether or not they have elevated aldosterone levels. Future studies will have to have more of these patients in the control group,” she said. She commented finally that whether or not renal denervation’s benefits will extend to other larger hypertension populations with less severe disease remains a major question.
The study, sponsored by Ardian, Inc., Mountain View, CA, appeared simultaneously in The Lancet. Volume 376, Issue 9756, Pages 1903 - 1909, 4 December 2010.