Safety and efficacy of a multi-electrode renal sympathetic denervation system in resistant hypertension: the EnligHTN I trial

Abstract

AimsCatheter-based renal artery sympathetic denervation has emerged as a novel therapy for treatment of patients with drug-resistant hypertension. Initial studies were performed using a single electrode radiofrequency catheter, but recent advances in catheter design have allowed the development of multi-electrode systems that can deliver lesions with a pre-determined pattern. This study was designed to evaluate the safety and efficacy of the EnligHTN™ multi-electrode system.Methods and resultsWe conducted the first-in-human, prospective, multi-centre, non-randomized study in 46 patients (67% male, mean age 60 years, and mean baseline office blood pressure 176/96 mmHg) with drug-resistant hypertension. The primary efficacy objective was change in office blood pressure from baseline to 6 months. Safety measures included all adverse events with a focus on the renal artery and other vascular complications and changes in renal function. Renal artery denervation, using the EnligHTN™ system significantly reduced the office blood pressure from baseline to 1, 3, and 6 months by −28/10, −27/10 and −26/10 mmHg, respectively (P < 0.0001). No acute renal artery injury or other serious vascular complications occurred. Small, non-clinically relevant, changes in average estimated glomerular filtration rate were reported from baseline (87 ± 19 mL/min/1.73 m2) to 6 months post-procedure (82 ± 20 mL/min/1.73 m2).ConclusionRenal sympathetic denervation, using the EnligHTN™ multi-electrode catheter results in a rapid and significant office blood pressure reduction that was sustained through 6 months. The EnligHTN™ system delivers a promising therapy for the treatment of drug-resistant hypertension.

Renal Denervation: Unde Venis et Quo Vadis?

“…However, only a lower blood pressure reduction of 11/ 7 mmHg compared to the control group was seen in the 20 patients of the HTN-2 study in whom an ambulatory blood pressure measurement was performed. 46 patients with treatment-resistant hypertension were treated in the prospective uncontrolled EnligHTN I study [40]. After 6 months a reduction of the systolic blood pressure of more than 10 mmHg (average 26 mmHg) and of the diastolic blood pressure of an average of 10 mmHg was seen in 76 % of the patients.…”

“…After 6 months a reduction of the systolic blood pressure of more than 10 mmHg (average 26 mmHg) and of the diastolic blood pressure of an average of 10 mmHg was seen in 76 % of the patients. 33 % of the patients reached the target blood pressure range of < 140 mmHg [40]. After renal denervation with the Paradise system (ReCor Medical) in which denervation is performed via ultrasound ablation instead of radiofrequency ablation, lowering of the office blood pressure by 36/17 mmHg or 22/12 mmHg in the ambulatory blood pressure measurement was observed after 3 months [41].…”

“…There are multiple possible explanations for the discrepancy in the blood pressure reduction between the HTN-3 study and the register data on the one hand and earlier studies that used the Symplicity catheter system on the other hand: 1. Lack of a control group: In the earlier, nonrandomized studies [40,51], the treatment results were compared to the initial, baseline blood pressure values of the same patient and not to a control group resulting in a false evaluation of the effectiveness of the treatment. 2.…”

“…In the three largest studies published before the HTN-3 study, a total of 305 patients were treated and followed-up [33,40,55]. New or progressive renal artery stenosis occurred in 6/305 (2.0 %) patients, renal artery dissection occurred in 1/305 (0.3 %) patients, complications in the region of the access path such as hematomas or aneurysms occurred in 12/305 (3.9 %) patients, and intraprocedural bradycardia occurred in 17/305 (5.6 %) patients [30,33,56].…”

“…Although the principle treatment approach of renal denervation is plausible on the basis of historic data, results from animal experiments [17,26] and human studies [15,19], the HTN-3 study as the first controlled, randomized, and blinded study after the initial positive study results [33,40,51] provided sobering information with respect to blood pressure reduction by renal denervation being superior to optimal treatment with medication [47]. If this is the end of renal denervation for treatment-resistant hypertension currently cannot be predicted.…”