Elsevier

The Lancet

Volume 385, Issue 9981, 16–22 May 2015, Pages 1957-1965
The Lancet

Articles
Optimum and stepped care standardised antihypertensive treatment with or without renal denervation for resistant hypertension (DENERHTN): a multicentre, open-label, randomised controlled trial

https://doi.org/10.1016/S0140-6736(14)61942-5Get rights and content

Summary

Background

Conflicting blood pressure-lowering effects of catheter-based renal artery denervation have been reported in patients with resistant hypertension. We compared the ambulatory blood pressure-lowering efficacy and safety of radiofrequency-based renal denervation added to a standardised stepped-care antihypertensive treatment (SSAHT) with the same SSAHT alone in patients with resistant hypertension.

Methods

The Renal Denervation for Hypertension (DENERHTN) trial was a prospective, open-label randomised controlled trial with blinded endpoint evaluation in patients with resistant hypertension, done in 15 French tertiary care centres specialised in hypertension management. Eligible patients aged 18–75 years received indapamide 1·5 mg, ramipril 10 mg (or irbesartan 300 mg), and amlodipine 10 mg daily for 4 weeks to confirm treatment resistance by ambulatory blood pressure monitoring before randomisation. Patients were then randomly assigned (1:1) to receive either renal denervation plus an SSAHT regimen (renal denervation group) or the same SSAHT alone (control group). The randomisation sequence was generated by computer, and stratified by centres. For SSAHT, after randomisation, spironolactone 25 mg per day, bisoprolol 10 mg per day, prazosin 5 mg per day, and rilmenidine 1 mg per day were sequentially added from months two to five in both groups if home blood pressure was more than or equal to 135/85 mm Hg. The primary endpoint was the mean change in daytime systolic blood pressure from baseline to 6 months as assessed by ambulatory blood pressure monitoring. The primary endpoint was analysed blindly. The safety outcomes were the incidence of acute adverse events of the renal denervation procedure and the change in estimated glomerular filtration rate from baseline to 6 months. This trial is registered with ClinicalTrials.gov, number NCT01570777.

Findings

Between May 22, 2012, and Oct 14, 2013, 1416 patients were screened for eligibility, 106 of those were randomly assigned to treatment (53 patients in each group, intention-to-treat population) and 101 analysed because of patients with missing endpoints (48 in the renal denervation group, 53 in the control group, modified intention-to-treat population). The mean change in daytime ambulatory systolic blood pressure at 6 months was −15·8 mm Hg (95% CI −19·7 to −11·9) in the renal denervation group and −9·9 mm Hg (−13·6 to −6·2) in the group receiving SSAHT alone, a baseline-adjusted difference of −5·9 mm Hg (−11·3 to −0·5; p=0·0329). The number of antihypertensive drugs and drug-adherence at 6 months were similar between the two groups. Three minor renal denervation-related adverse events were noted (lumbar pain in two patients and mild groin haematoma in one patient). A mild and similar decrease in estimated glomerular filtration rate from baseline to 6 months was observed in both groups.

Interpretation

In patients with well defined resistant hypertension, renal denervation plus an SSAHT decreases ambulatory blood pressure more than the same SSAHT alone at 6 months. This additional blood pressure lowering effect may contribute to a reduction in cardiovascular morbidity if maintained in the long term after renal denervation.

Funding

French Ministry of Health.

Introduction

Endovascular renal denervation with radiofrequency ablation has emerged as a new invasive treatment for patients with resistant hypertension to a multiple antihypertensive drug regimen.1 The first two studies of renal denervation reported 25–30 mm Hg decreases in office systolic blood pressure at 6 months in patients with resistant hypertension, with less than 5% of patients having procedural adverse events.2, 3 Subsequently, the procedure was made available in Europe4, 5, 6 despite uncertainty about both safety and efficacy related to the limitations of most previous studies (no standardisation of blood pressure measurements and antihypertensive treatment, and their single-arm observational study design).7, 8 The indications, risk-benefit ratio, and cost-effectiveness of renal denervation compared with an optimum medical strategy, therefore, still need to be assessed in a setting with a more precise identification of the target population with resistant hypertension.7, 8 We designed this Renal Denervation for Hypertension (DENERHTN) trial to assess the ambulatory blood pressure-lowering efficacy, safety, and cost-effectiveness of renal denervation added to a standardised stepped-care antihypertensive treatment (SSAHT) recommended by UK guidelines9 compared with the same SSAHT alone in patients with confirmed resistant hypertension. We report here the 6-month blood pressure-lowering efficacy and safety results.

Section snippets

Study design and patients

The DENERHTN study is a multicentre, open-label, randomised, controlled trial with blinded endpoint assessment. Between May 22, 2012, and Oct 14, 2013, we recruited participants from 15 French tertiary care centres specialised for hypertension management, which were qualified to do renal denervation. Approval needed both previous expertise of the onsite interventionalist in renal angiography or stenting and training and supervision by the lead interventionalist (appendix). 14 of these

Results

1416 patients with resistant hypertension to three or more antihypertensive drugs on the basis of their office blood pressure were assessed for eligibility. 121 patients (8·5%) with supine office blood pressure of 163·4 mm Hg (SD 23·0)/95·0 mm Hg (12·7) despite being treated with four (IQR 3–5) different antihypertensive drugs (diuretic, 94·2%; renin angiotensin system blockers, 95·9%; calcium channel blockers, 97·5%; β blockers, 35·5%; aldosterone antagonists, 23·1%; centrally acting

Discussion

In patients with confirmed resistant hypertension, renal denervation combined with SSAHT reduced 6-month daytime (primary endpoint), night-time, and 24-h ambulatory systolic blood pressure significantly more (by about 6 mm Hg) than the same SSAHT alone (panel). Subsequently, the 6-month ambulatory blood pressure control rate was higher in the renal denervation group than in the control group. Even though the study was not double-blinded (there was no sham procedure), the need to add-on new

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