Elsevier

The Lancet

Volume 376, Issue 9756, 4–10 December 2010, Pages 1903-1909
The Lancet

Fast track — Articles
Renal sympathetic denervation in patients with treatment-resistant hypertension (The Symplicity HTN-2 Trial): a randomised controlled trial

https://doi.org/10.1016/S0140-6736(10)62039-9Get rights and content

Summary

Background

Activation of renal sympathetic nerves is key to pathogenesis of essential hypertension. We aimed to assess effectiveness and safety of catheter-based renal denervation for reduction of blood pressure in patients with treatment-resistant hypertension.

Methods

In this multicentre, prospective, randomised trial, patients who had a baseline systolic blood pressure of 160 mm Hg or more (≥150 mm Hg for patients with type 2 diabetes), despite taking three or more antihypertensive drugs, were randomly allocated in a one-to-one ratio to undergo renal denervation with previous treatment or to maintain previous treatment alone (control group) at 24 participating centres. Randomisation was done with sealed envelopes. Data analysers were not masked to treatment assignment. The primary effectiveness endpoint was change in seated office-based measurement of systolic blood pressure at 6 months. Primary analysis included all patients remaining in follow-up at 6 months. This trial is registered with ClinicalTrials.gov, number NCT00888433.

Findings

106 (56%) of 190 patients screened for eligibility were randomly allocated to renal denervation (n=52) or control (n=54) groups between June 9, 2009, and Jan 15, 2010. 49 (94%) of 52 patients who underwent renal denervation and 51 (94%) of 54 controls were assessed for the primary endpoint at 6 months. Office-based blood pressure measurements in the renal denervation group reduced by 32/12 mm Hg (SD 23/11, baseline of 178/96 mm Hg, p<0·0001), whereas they did not differ from baseline in the control group (change of 1/0 mm Hg [21/10], baseline of 178/97 mm Hg, p=0·77 systolic and p=0·83 diastolic). Between-group differences in blood pressure at 6 months were 33/11 mm Hg (p<0·0001). At 6 months, 41 (84%) of 49 patients who underwent renal denervation had a reduction in systolic blood pressure of 10 mm Hg or more, compared with 18 (35%) of 51 controls (p<0·0001). We noted no serious procedure-related or device-related complications and occurrence of adverse events did not differ between groups; one patient who had renal denervation had possible progression of an underlying atherosclerotic lesion, but required no treatment.

Interpretation

Catheter-based renal denervation can safely be used to substantially reduce blood pressure in treatment-resistant hypertensive patients.

Funding

Ardian.

Introduction

Successful treatment of raised blood pressure has proven elusive despite availability of various drugs, combination pharmaceutical products, and resources to assist patients' adherence and lifestyle changes. In about half of hypertensive patients, blood pressure remains higher than accepted treatment targets despite broad availability of effective pharmaceutical agents.1, 2 The failure of present strategies suggests underlying pathophysiology that is refractory to available pharmacological interventions, inherent limitations of present pharmacological strategy, physician inertia, or antipathy of patients to lifelong multidrug treatment for a predominantly asymptomatic disease.

Renal sympathetic nerves contribute to development and perpetuation of hypertension, and sympathetic outflow to the kidneys is activated in patients with essential hypertension.3 Efferent sympathetic outflow stimulates renin release, increases tubular sodium reabsorption, and reduces renal blood flow.4 Afferent signals from the kidney modulate central sympathetic outflow and thereby directly contribute to neurogenic hypertension.5, 6, 7

Non-selective surgical sympathectomy was effectively used as a treatment of severe hypertension before antihypertensive drugs became generally available.8, 9 Recently developed endovascular catheter technology enables selective denervation of the human kidney, with radiofrequency energy delivered in the renal artery lumen, accessing the renal nerves located in the adventitia of the renal arteries. A first-in-man study of this approach10 showed successful renal denervation with reduction of sympathetic activity and renin release in parallel with reductions of central sympathetic outflow. Safety and feasibility trials of this procedure identified substantial reductions of blood pressure without substantial procedure-related complications.11 We report results from a randomised trial that aimed to show that catheter-based renal denervation could safely reduce blood pressure in patients with treatment-resistant hypertension.

Section snippets

Study design and patients

Symplicity HTN-2 was an international, multicentre, randomised study of the safety and effectiveness of renal denervation in patients with treatment-resistant hypertension. Patients aged 18–85 years with a systolic blood pressure of 160 mm Hg or more (≥150 mm Hg in patients with type 2 diabetes), despite compliance with three or more antihypertensive drugs, were eligible for inclusion. Exclusion criteria included an estimated glomerular filtration rate (eGFR; based on the Modification of Diet

Results

From June 9, 2009, to Jan 15, 2010, 106 (56%) of 190 patients screened were eligible for study inclusion and were randomly allocated to renal denervation or control groups (figure 1). Patients in the two study groups did not differ by age, sex, baseline systolic or diastolic blood pressure, race, most comorbidities, and reported duration spent on antihypertensive therapy (table 1). Patients in the renal denervation group had a lower baseline renal function than did the control group, as

Discussion

Our study supports previous uncontrolled investigations11, 15 that showed a significant reduction in blood pressure can be achieved with catheter-based renal denervation in patients whose essential hypertension was uncontrolled despite treatment with three or more antihypertensive drugs (panel). This benefit was evident by the concordance of measurements of office blood pressure, home blood pressure, and 24-h ambulatory blood-pressure monitoring. Measurements made in parallel in the comparator

References (32)

  • RH Smithwick et al.

    Splanchnicectomy for essential hypertension; results in 1,266 cases

    J Am Med Assoc

    (1953)
  • MP Schlaich et al.

    Renal sympathetic-nerve ablation for uncontrolled hypertension

    N Engl J Med

    (2009)
  • AS Levey et al.

    A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of diet in renal disease study group

    Ann Intern Med

    (1999)
  • AV Chobanian et al.

    Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure

    Hypertension

    (2003)
  • G Mancia et al.

    2007 Guidelines for the management of arterial hypertension: the Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC)

    Eur Heart J

    (2007)
  • M Schlaich et al.

    Two-year durability of blood pressure reduction with catheter-based renal sympathetic denervation

    J Hypertens

    (2010)
  • Cited by (1947)

    • Device's design and clinical perspectives for resistant hypertension therapy

      2024, International Journal of Cardiology: Cardiovascular Risk and Prevention
    • The Ongoing Odyssey of Renal Denervation

      2023, Journal of the American College of Cardiology
    View all citing articles on Scopus

    Members listed at end of paper

    View full text