“Is a cure for hypertension now possible?” Professor Murray Esler's speculation on the future of antihypertensive therapy comes in the wake of a study he and his fellow Symplicity HTN-2 Investigators have published in the Lancet. The first randomized controlled trial of renal sympathetic denervation in drug-resistant patients with hypertension has demonstrated that this catheter-based procedure is safe and effective.

Despite the numerous available drugs and resources for lifestyle modification, approximately half of all patients with hypertension do not achieve their blood-pressure target. Whether a result of physiological resistance to the pharmaceutical agents, or to patients' reluctance to adhere to lifelong pharmacological treatments, the prevalence of drug-resistant high blood pressure is clearly a problem.

Professor Esler, from the Baker IDI Heart & Diabetes Institute in Melbourne, Australia, and others have previously demonstrated that the renal sympathetic nerves are often excessively activated in patients with essential hypertension. Furthermore, surgical sectioning of the renal nerves has been shown to reduce or normalize elevated blood pressure in animal models of this disease. Now, the first randomized controlled trial of selective catheter-based, renal sympathetic denervation has been performed in 24 centers in Europe, Australia, and New Zealand.

To be eligible for the study, patients had to demonstrate compliance with three or more antihypertensive drugs over a 2-week period, but still have a systolic blood pressure ≥160 mmHg (or ≥150 mmHg in those with type 2 diabetes mellitus). Individuals who had previously undergone renal artery intervention, or had hemodynamically significant renal artery stenosis or renal artery anatomy that precluded treatment, were excluded from the trial.

The Symplicity® Catheter System is manufactured by Ardian (Mountain View, CA, USA), the trial sponsors. The investigators used a femoral-artery access point to deliver radiofrequency energy along the length of both main renal arteries, thereby ablating the renal nerves in the adventitia. All patients remained on their preintervention antihypertensive drug regimen throughout the study, unless changes to the regimen were judged medically necessary.

The primary end point (between-group change in average office-based measures of systolic blood pressure from baseline to the 6-month follow-up) was assessed for 49 patients randomly assigned to undergo renal denervation and 51 individuals randomly assigned to the control group. Compared with the controls, the renal-denervation group had a 33/11 mmHg reduction in blood pressure (P <0.0001 for both systolic and diastolic blood pressure). Home-based blood-pressure measurements were also reduced in those who underwent renal denervation; the absolute difference between the groups at home was 22/12 mmHg (P <0.0001 for both systolic and diastolic blood pressure). Drug reductions before the 6-month follow-up were noted for 20% and 6% of those in the renal-denervation and control groups, respectively (P = 0.04). No serious complications were observed and renal function was unchanged in both groups.

The Symplicity® system has been approved for treatment of patients with drug-resistant hypertension in Europe and Australia, and will be tested for approval in a randomized clinical trial in the USA. In the foreseeable future, renal denervation will also be assessed in patients with milder forms of this disease.