Is Renal Denervation Effective in Treating Resistant Hypertension?

A New Era of Renal Denervation Trials for Patients With Hypertension?

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

Long-term outcomes after catheter-based renal artery denervation for resistant hypertension: final follow-up of the randomised SYMPLICITY HTN-3 Trial

Data at 36 months for the Symplicity SPYRAL HTN-ON MED pilot – Authors' reply

SYMPLICITY HTN-3: failure at 6 months, success at 3 years?

Catheter-Based Renal Denervation in ADPKD: Just for Pain Control?

Background Recent studies have shown proven efficacy of renal denervation in arterial hypertension, but there is a continuing need to assess the duration of antihypertensive effect. Purpose Evaluation of the long-term antihypertensive effect of renal denervation in patients with resistant hypertension. Methods 125 apparently resistant patients without comorbidities after a 3-week standardized treatment with Losartan 100 mg, Amlodipin 10 mg and Indapamid 1.5 mg and confirmation of their resistance were randomly assigned into three groups depending on treatment supplemented to previously administered: group I - selective I1-imidazoline agonist Moxonidine, group II - cardioselective beta-blocker Bisoprolol and group III – renal artery denervation. The compliance to treatment was confirmed using 8-item Morisky Medication Adherence Scale. Renal denervation was performed in the main renal arteries and their branches. Patients were assessed by ambulatory blood pressure monitoring at baseline, 3, 12, 24 and 36 months follow-up. Results The mean 24 hour systolic blood pressure (SBP) at baseline were 179.0±2.02 mmHg in group I versus 177.96±2.44 mmHg in group II and 176.92±1.97 mmHg in group III, p>0.05. A statistically significant reduction in SBP m/24 h was noted in all three groups starting at 3 months, the group of patients undergoing renal denervation showing superiority over both groups of pharmacological treatment: −6.48±0.81 mmHg in group I versus −6.2±0.88 mmHg in group II and −23.28±1.9 mmHg in group III, p<0.001. The progressive improvement continued until the end of the study, so at 3 years of evaluation in observational group supplemented with Moxonidine SBP m/24 h were 146.36±1.36 mmHg with a total reduction of −32.64±1.56 mmHg from baseline, in Bisoprolol group −152.88±1.56 mmHg with a reduction of −25.08±1.65 mmHg and 133.16±0.73 mmHg in renal denervation group with a total reduction of −282±1.30 mmHg in group III, p<0.001. The mean 24 hour diastolic blood pressure (DBP) increased at baseline in all three observational groups (105.52±1.28 mmHg in group I versus 108.6±1.6 mmHg in group II and 107.24±0.92 mmHg in group III, p>0.05) similar with SBP m/24 h noted an authentic reduction at 3 months follow-up. The maximum reduction in DBP m/24 h were registered at 3 years of evaluation, a comparative analyses of dynamics between groups showing a presence of statistical difference due to superiority of renal denervation in amelioration of this parameter: −18.36±1.88 mmHg in group I versus −16.84±1.76 mmHg in group II and −28.2±1.30 mmHg in group III, p<0.001. Conclusions All three regimens have been shown to be effective in reducing SBP and DBP m/24 h in patients with resistant hypertension, with a superior but comparable effect of Moxonidine to Bisoprolol and the absolute superiority of renal denervation treatment, the beneficial effect being maintained for a period of 3 years. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): National Agency for Research and Development

The link between renal denervation and reduction of cardiovascular risks: Simplicity or not?

Trial: Symplicity HTN-2 Investigators, Esler MD, Krum H, et al.: Renal sympathetic denervation in patients with treatment-resistant hypertension (The Symplicity HTN-2 Trial): a randomized controlled trial. Lancet 2010, 376:1903–1909. Rating: ••Of major importance. Introduction: Sympathetic overactivity is thought to be a major contributor to the pathogenesis and progression of human hypertension [1, 2]. In particular, renal sympathetic activation results in renal vasoconstriction, increased renin secretion, and enhanced sodium and water reabsorption, all of which contribute to the development of hypertension [3]. Despite this mechanistic understanding, attempts at modulating sympathetic tone with antiadrenergic drug therapy have been limited by their poor clinical performance and undesirable side-effect profile [1, 4]. Additionally, historic surgical approaches for the treatment of hypertension with renal sympathectomy have long been abandoned due to a high perioperative morbidity and mortality [5, 6]. In recent years, the advent of a catheter-based technique using radiofrequency to destroy the renal nerves has revitalized these long abandoned thoughts of treating hypertension with renal denervation. Following encouraging results of an uncontrolled feasibility trial and a case report [7, 8], a recent randomized controlled trial (Symplicity HTN-2 [Renal Denervation in Patients With Uncontrolled Hypertension]) has further demonstrated the potential for catheter-based renal denervation in the treatment of drug-resistant hypertension. Aims: The Symplicity HTN-2 trial was designed to determine the safety and effectiveness of catheter-based renal artery denervation with the Symplicity Catheter System (Ardian, Palo Alto, CA) in reducing blood pressure in patients with drug-resistant hypertension. Methods: In this multicenter trial (involving 24 centers in Europe, Australia, and New Zealand), 106 patients ages 18 to 85 years with a systolic blood pressure of 160 mm Hg or more (≥150 mm Hg in patients with type 2 diabetes), despite treatment with three or more antihypertensive medications were randomized to undergo renal denervation while continuing prior drug therapy or to continue prior drug therapy alone. Patients who met initial screening criteria were subsequently excluded from the trial if their blood pressure fell below eligibility criteria at a second clinic visit after a 2-week screening phase. During this phase, patients were required to document medication compliance and twice-daily home blood pressure monitoring. Patients were also excluded if they were found to have unfavorable renal artery anatomy on imaging; other exclusion criteria included an estimated glomerular filtration rate of less than 45 mL/min/1.73 m2 and type 1 diabetes. The trial’s primary end point was the change from baseline in seated office-based measurement of systolic blood pressure at 6 months. During the intervention, the catheter was advanced into the renal arteries and four to six discrete low-power radiofrequency treatments were applied along the length of both renal arteries. Background use of antihypertensive drugs was held constant for the duration of the trial in both groups. Results: At baseline, the groups were well matched on most characteristics: office blood pressure was 178/96 mm Hg in the intervention group (n = 52) and 178/97 mm Hg in the control group (n = 54). Office-based blood pressure fell by 32/12 mm Hg (SD 23/11; P < 0.001) in the patients who underwent renal denervation versus no change in the control group (1/0 mm Hg, SD 21/10; P = NS). Home blood pressure fell by 20/12 mm Hg (SD 17/11) in the renal denervation group (n = 32) versus no change in the control group (n = 40). Twenty-four-hour ambulatory blood pressure fell by 11/7 mm Hg (SD 15/11; P < 0.006) in the renal denervation group (n = 20) versus no change in the control group (n = 25). There were no serious procedural complications in the denervation group and no between-group differences in renal function or in the incidence of adverse events. Discussion: The authors concluded that renal artery denervation is safe and effective in reducing office blood pressure, home blood pressure, and 24-h blood pressure at 6 months in patients with drug-resistant hypertension.

Renal denervation in hypertension patients: Proceedings from an expert consensus roundtable cosponsored by SCAI and NKF.

Background/Introduction Renal denervation (RDN) is an innovative procedure designed to regulate the renal sympathetic nervous system for the control of arterial hypertension (HTN). RDN emerges as an alternative for patients with resistant arterial hypertension. Despite this, the clinical efficacy of RDN is still not fully understood. Purpose Therefore, we aimed to compare the use of renal denervation versus sham procedure or pharmacological treatment in patients with resistant HTN. Methods We performed a systematic search of PubMed, Embase, Cochrane databases for randomized controlled trials (RCTs) comparing the use of renal denervation procedures and sham procedure or pharmacological treatment in patients with resistant HTN. Statistical analyses were performed using R Studio 4.3.2. Heterogeneity was examined with the Cochran Q test I² statistics. Mean difference (MD) with 95% CI were pooled across trials. P values of &amp;lt; 0.05 were considered statistically significant. The primary continuous outcomes of interest were change from baseline in systolic blood pressure (SBP), diastolic blood pressure (DBP) and serum creatinine. Results Twenty-one RCTs reporting data on 3345 patients were included in this meta-analysis. Among them, 2004 (59,91%) received renal denervation and 1341 (40,09%) received pharmacological treament or sham procedure. Follow-up ranged from 2 to 48 months. The mean age of patients between studies ranged from 50.7 to 65 years. Compared to control group, RDN significantly reduced Systolic Blood Pressure (SBP) (MD -3.53 mmHg; 95% CI -5.94 to -1.12; I2 = 74%) and Diastolic Blood Pressure (DBP) (MD -1.48 mmHg; 95% CI -2.56 to -0.40; I2 = 51%). Regarding serum creatinine (MD -2.51; 95% CI -7.90 to 2.87; I2 = 40%) there was no significant difference between RDN and control groups. Conclusion In this meta-analysis of RCTs of patients with resistant HTN, RDN was associated with a reduction in SBP and DBP compared to sham procedure or pharmacological treatment.

It has been postulated that catheter-based renal denervation (RDN) may lower blood pressure (BP) and improve severity of obstructive sleep apnea (OSA) in resistant hypertensive patients. The aim of our study (NCT01366625) was to investigate in a prospective randomized trial the effect of RDN on BP and clinical course of OSA. Sixty patients with true resistant hypertension coexisting with moderate-to-severe OSA (apnea/hypopnea index, ≥15) were randomly allocated to RDN group (30 patients) and to control group (30 patients). The primary end point was reduction in office systolic BP at 3 months. Secondary end points included reduction in diastolic office and ambulatory BP, change in apnea/hypopnea index and biochemical measurements at 3 months, and change in echocardiographic measurements at 6 months. There were no differences in clinical characteristics between the groups. At 3 months in the RDN group, both office and ambulatory BP were significantly reduced, and a significant decrease in OSA severity (apnea/hypopnea index, 39.4 versus 31.2 events per hour; P =0.015) was observed. Between-group difference in apnea/hypopnea index change was significant at 0.05. At 6 months in the RDN group, reductions in office and ambulatory BP were sustained and were accompanied by significant improvement in echocardiographic measures of global longitudinal strain. There were no differences in metabolic variables in follow-up in both groups. In a randomized controlled trial, RDN lowered both office and ambulatory BP in patients with resistant hypertension and OSA. This was accompanied by improvement of the clinical severity of OSA. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT01366625.

<i>Hypertension</i> Editors’ Picks

Blood pressure target goals from guidelines of 2002-2014.

Background. Diabetic patients with resistant hypertension (RHT) are characterized by a high rate of annual decline in estimated glomerular filtration rate (eGFR) (up to 14 mL/min/1.73 m 2 ). The distal approach to sympathetic renal denervation (RD) reduces blood pressure (BP) to a greater extent compared with standard RD. However, the long-term effect of distal RD on the renal function remains unknown. Aim . The purpose of this study was to evaluate the long-term safety and nephroprotective efficacy profile of distal RD compared to conventional intervention in RHT patients with type 2 diabetes mellitus (T2DM) during a three-year follow-up. Material and Methods. Twenty seven patients (eight men) with true RHT and T2DM were included in a single-arm prospective interventional study (number NCT01499810 at ClinicalTrials.gov) (mean age of 61.6 ± 7.3 years; mean office (systolic/diastolic) BP of 171.8 ± 21.9/87.7 ± 17.7 mmHg; mean eGFR of 72.1 ± 19.9 mL/min/1.73 m²; and glycosylated hemoglobin level (HbA1c) of 6.3 ± 1.1%). Patients were randomized into two comparable groups of distant ( n = 13) and standard RD ( n = 14). Office BP, ABPM, renal Doppler ultrasound, renal function (eGFR (CKD-EPI) and 24-hour urinary albumin excretion (UAE)), and kidney MRI were assessed at baseline and annually during a three-year follow-up. Nineteen patients completed a 36-month follow-up (8 patients were treated by distal RD and 11 patients received the conventional procedure). Results. The change in eGFR during three-year follow-up was insignificant in group of distal RD (-5.3 ± 0.4 mL/min/1.73 m 2 , p = 0.63) and was comparable with the corresponding value in conventional RD group (–6.7 ± 4.2 mL/min/1.73 m 2 , p = 0.3), ( p = 0.7 for intergroup comparison) despite a more powerful decrease in 24-h systolic BP in the distal RD group relative to that in conventional RD group (–25.3 ± 15.3 vs. 4.4 ± 22 mmHg, p = 0.04). The degrees of annual decline in GFR did not differ between the distal RD group and conventional RD group ( p = 0.9) and were –2.7 ± 2.4 mL/min/1.73 m 2 /year and –2.7 ± 4.0 mL/min/1.73 m 2 /year, respectively. No significant changes in renal blood flow, albuminuria, MRI-based kidney size, and the number of patients with albuminuria and renal dysfunction were found during the study. Conclusions. Distal RDN in diabetic patients with RHT had a three-year safety profile and nephroprotective efficacy similar to those when the standard method was used despite a more significant reduction of blood pressure. Both modes of RD are likely to slow the progression of renal dysfunction in these patients.