Radiofrequency Renal Denervation Research Articles

F-5 | Long-term Outcomes Following Radiofrequency Renal Denervation: Meta-analysis of 18 Reports with Patient Level Data from the Global Symplicity Registry DEFINE

F-5 | Long-term Outcomes Following Radiofrequency Renal Denervation: Meta-analysis of 18 Reports with Patient Level Data from the Global Symplicity Registry DEFINE

Long-Term Safety and Efficacy of Transcatheter Microwave and Radiofrequency Denervation in a Chronic Ovine Model.

Transcatheter renal denervation (RDN) has had inconsistent efficacy and concerns for durability of denervation. We aimed to investigate long-term safety and efficacy of transcatheter microwave RDN invivo in normotensive sheep in comparison to conventional radiofrequency ablation. Sheep underwent bilateral RDN, receiving 1 to 2 microwave ablations (maximum power of 80-120 W for 240 s-480 s) and 12 to 16 radiofrequency ablations (180 s-240 s) in the main renal artery in a paired fashion, alternating the side of treatment, euthanized at 2 weeks (acute N=15) or 5.5 months (chronic N=15), and compared with undenervated controls (N=4). Microwave RDN produced substantial circumferential perivascular injury compared with radiofrequency at both 2 weeks [area 239.8 (interquartile range [IQR] 152.0-343.4) mm2 versus 50.1 (IQR, 32.0-74.6) mm2, P <0.001; depth 16.4 (IQR, 13.9-18.9) mm versus 7.5 (IQR, 6.0-8.9) mm P <0.001] and 5.5 months [area 20.0 (IQR, 3.4-31.8) mm2 versus 5.0 (IQR, 1.4-7.3) mm2, P=0.025; depth 5.9 (IQR, 1.9-8.8) mm versus 3.1 (IQR, 1.2-4.1) mm, P=0.005] using mixed models. Renal denervation resulted in significant long-term reductions in viability of renal sympathetic nerves [58.9% reduction with microwave (P=0.01) and 45% reduction with radiofrequency (P=0.017)] and median cortical norepinephrine levels [71% reduction with microwave (P <0.001) and 72.9% reduction with radiofrequency (P <0.001)] at 5.5 months compared with undenervated controls. Transcatheter microwave RDN produces deep circumferential perivascular ablations without significant arterial injury to provide effective and durable RDN at 5.5 months compared with radiofrequency RDN.

428 Three-year nighttime blood pressure after radiofrequency renal denervation in patients with uncontrolled hypertension and chronic kidney disease

428 Three-year nighttime blood pressure after radiofrequency renal denervation in patients with uncontrolled hypertension and chronic kidney disease

427 Meta-analysis of long-term outcomes following radiofrequency renal denervation

427 Meta-analysis of long-term outcomes following radiofrequency renal denervation

429 Reductions in Blood Pressure after Radiofrequency Renal Denervation Stratified by Patient Age: 12- Month Results from the Symplicity SPYRAL program

429 Reductions in Blood Pressure after Radiofrequency Renal Denervation Stratified by Patient Age: 12- Month Results from the Symplicity SPYRAL program

A novel, proof-of-concept radiofrequency renal denervation strategy to improve procedural efficiency: 12-month results from the SPYRAL DYSTAL pilot study

BackgroundCatheter-based renal sympathetic denervation (RDN) reduced blood pressure (BP) in multiple randomized sham-controlled trials of patients with uncontrolled hypertension (HTN). We tested proof-of-concept for a more selective treatment strategy, exclusively targeting these areas to improve the efficiency of the procedure. MethodsThe SPYRAL DYSTAL Pilot study was designed to mirror the SPYRAL HTN-OFF MED Pivotal study, enabling comparison with a propensity score adjusted active-control group. Patients were antihypertensive medication-free for one month before undergoing BP assessment. Those with office BP of 150–180/>90 mmHg and with an ambulatory systolic BP of 140–170 mmHg were selected to undergo open label treatment, delivering energy only to the distal main renal arteries and first order branches. Patients from DYSTAL were compared with patients who underwent maximized RF RDN treatment in the prior randomized OFF MED trial at 3 months. After 3 months, patients resumed antihypertensive medications as indicated. Safety and efficacy outcomes were assessed post hoc through 12 months. ResultsThe SPYRAL DYSTAL Pilot study treated 56 HTN patients. Baseline office systolic BP (OSBP) and 24-h ambulatory systolic BP (ASBP) were similar between DYSTAL and OFF MED patient groups. The number of ablations (32.3 ± 8.0 vs 46.6 ± 15.3, p < 0.001), procedure time (67 ± 21 min vs 99 ± 36 min; p < 0.001), and contrast volume (173 ± 77 cc vs 208 ± 96 cc; p = 0.014) were significantly lower with the simplified treatment strategy. OSBP and ASBP changes compared with baseline were −9.0 and −1.4 mmHg at 3 months, −20.3 and −13.9 mmHg at 6 months, and −20.3 and −16.6 mmHg at 12 months, respectively. During the medication up-titration phase, BP reductions among DYSTAL patients were similar to reductions observed in OFF MED through 12 months, with comparable number of drugs (1.4 and 1.5 medications, respectively (P=NS)). Two adverse events related to guidewire placement were reported. ConclusionIn this pilot study, focusing ablation treatment on the distal main and proximal branch renal arteries was performed, resulting in fewer RF lesions, and reduced contrast volume and procedure time. Whether BP reductions are similar between a selective vs. maximized RDN approach requires further prospective study.

Ultra-long-term efficacy and safety of catheter-based renal denervation in resistant hypertension: 10-year follow-up outcomes.

Randomized sham-controlled trials have confirmed the efficacy and safety of catheter-based renal denervation in hypertension. Data on the very long-term effects of renal denervation are scarce. This study evaluates the 10-year safety and efficacy of renal denervation in resistant hypertension. This prospective single-center study included patients with resistant hypertension undergoing radio-frequency renal denervation between 2010 and 2012. Office blood pressure, 24-h ambulatory blood pressure, antihypertensive medication, color duplex sonography, and renal function were assessed after 1-, 2- and 10-years. Thirty-nine patients completed the 10-year follow-up (mean follow-up duration 9.4 ± 0.7years). Baseline office and 24-h ambulatory systolic blood pressure were 164 ± 23mmHg and 153 ± 16mmHg, respectively. After 10years, 24-h ambulatory and office systolic blood pressure were reduced by 16 ± 17mmHg (P < 0.001) and 14 ± 23mmHg (P = 0.001), respectively. The number of antihypertensive drugs remained unchanged from 4.9 ± 1.4 to 4.5 ± 1.2 drugs (P = 0.087). The estimated glomerular filtration rate declined within the expected range from 69 (95% CI 63 to 74) to 60mL/min/1.73m2 (95% CI 53 to 68; P < 0.001) through 10-year follow-up. Three renal artery interventions were documented for progression of pre-existing renal artery stenosis in two patients and one patient with new-onset renal artery stenosis. No other adverse events were observed during the follow-up. Renal denervation was safe and sustainedly reduced ambulatory and office blood pressure out to 10years in patients with resistant hypertension.

Early Renal Denervation Attenuates Cardiac Dysfunction in Heart Failure With Preserved Ejection Fraction.

The renal sympathetic nervous system modulates systemic blood pressure, cardiac performance, and renal function. Pathological increases in renal sympathetic nerve activity contribute to the pathogenesis of heart failure with preserved ejection fraction (HFpEF). We investigated the effects of renal sympathetic denervation performed at early or late stages of HFpEF progression. Male ZSF1 obese rats were subjected to radiofrequency renal denervation (RF-RDN) or sham procedure at either 8 weeks or 20 weeks of age and assessed for cardiovascular function, exercise capacity, and cardiorenal fibrosis. Renal norepinephrine and renal nerve tyrosine hydroxylase staining were performed to quantify denervation following RF-RDN. In addition, renal injury, oxidative stress, inflammation, and profibrotic biomarkers were evaluated to determine pathways associated with RDN. RF-RDN significantly reduced renal norepinephrine and tyrosine hydroxylase content in both study cohorts. RF-RDN therapy performed at 8 weeks of age attenuated cardiac dysfunction, reduced cardiorenal fibrosis, and improved endothelial-dependent vascular reactivity. These improvements were associated with reductions in renal injury markers, expression of renal NLR family pyrin domain containing 3/interleukin 1β, and expression of profibrotic mediators. RF-RDN failed to exert beneficial effects when administered in the 20-week-old HFpEF cohort. Our data demonstrate that early RF-RDN therapy protects against HFpEF disease progression in part due to the attenuation of renal fibrosis and inflammation. In contrast, the renoprotective and left ventricular functional improvements were lost when RF-RDN was performed in later HFpEF progression. These results suggest that RDN may be a viable treatment option for HFpEF during the early stages of this systemic inflammatory disease.

Progression of obstructive sleep apnoea after renal denervation is not associated with hypertension exaggeration

PurposeIn a cohort, observational prospective trial, we assessed the long-term dynamics of sleep-disordered breathing in patients with resistant hypertension after renal denervation and their association with blood pressure change at remote follow-up.Materials and methodsTwenty-eight patients with stable hypertension who were recruited for endovascular radiofrequency renal denervation in 2012–2019 and had valid both baseline and follow-up sleep study, were included in the analysis. All patients underwent physical examination, anthropometry, office and ambulatory blood pressure measurements, blood and urine tests, kidney visualization, and full polysomnography before and within 12–36 months after renal denervation.ResultsThe average follow-up comprised 30.1 ± 8.4 months. At long-term follow-up, no significant changes in creatinine level, estimated glomerular filtration rate, body mass index were registered. There was a significant increase in sleep apnea severity indices: the mean change in apnea-hypopnea index comprised 9.0(-21.1;25.2) episodes/h, in oxygen desaturation index 6.5(-16.8;35.9) episodes/h, in the average SpO2 -1.7(-5.6;1.9)%. Over 12-month follow-up, there were no significant differences in blood pressure response in patients with and without sleep apnea. The baseline apnea-hypopnea and oxygen desaturation indices and the mean SpO2 were associated with the circadian blood pressure profile at follow-up, but did not correlate with the blood pressure response.ConclusionsAlthough the severity of sleep apnea worsens at > 12 months follow-up after renal denervation, this is not associated with hypertension exaggeration.

Improved health-related quality of life after renal denervation in patients with resistant hypertension: 3-year outcomes in the global symplicity registry

Abstract Background Hypertension is associated with increased mental anxiety and depression. Renal denervation (RDN) reduces blood pressure (BP) in patients with uncontrolled, resistant hypertension (rHTN). The Global SYMPLICITY Registry (GSR) DEFINE is a prospective, open-label, single-arm, all-comer worldwide study, enrolling patients to undergo RDN. Whether BP reductions after RDN improve patients’ self-reported health and quality of life through long-term follow-up remains elusive. Purpose To evaluate changes in self-reported health and quality of life of rHTN patients following radiofrequency RDN. Methods GSR DEFINE patients completed the EuroQoL five-dimensions three-level (EQ-5D) questionnaire to assess their own health state on a visual analog scale (VAS: 0 to 100, with 0 being ‘worst possible’ and 100 being ‘best possible'). Patients were also asked to assess five dimensions of quality of life including mobility, self-care, usual activities, pain/discomfort, anxiety/depression at 3 levels: no problems (score: 0), some problems (1), severe problems (2). Patients answered the questionnaire at 6, 12, 24, and 36-month follow-up after the RDN procedure. Categorical measures from the pooled results of the questionnaire between subgroups were compared using the Kruskal-Wallis test. Here we assess the self-reported health state and quality of life measures among patients with rHTN (office systolic BP ≥150 mmHg and on ≥3 antihypertensive drugs) at baseline through 36 months. Results At baseline, GSR patients with rHTN (n=2051) had an office systolic blood pressure (OSBP) of 175.2 ± 19.8 mmHg and a 24-h ambulatory systolic blood pressure (ASBP) of 157.4 ± 18.6 mmHg. At 36 months after RDN, rHTN patients had significant reductions in OSBP (-23.5 ± 27.0 mmHg; n=906; p&amp;lt;0.001) and ASBP (-10.3 ± 20.9 mmHg; n=329; p&amp;lt;0.001), respectively. Antihypertensive medication remained unchanged through 36 months. Correspondingly, patients with rHTN reported a significant improvement in the self-reported health state from baseline after RDN at each follow-up through 36 months (Figure). At baseline (n=1813), patients with rHTN reported a 0.86 ± 0.20 EQ-5D quality of life score. At 36 months (n=839), patients with rHTN reported an improved quality of life with a 0.85 ± 0.21 score which was a statistically significant change from baseline (p=0.0024). Conclusion Following RDN, self-reported health state and quality of life data from a large population of rHTN patients improved from baseline through 36-months. These results suggest that BP reductions following radiofrequency RDN may alleviate mental anxiety and depression associated with hypertension.

Comparative evaluation of renal denervation versus pharmacological treatment on diastolic function in patients with resistant hypertension: three years follow-up

Abstract Background Several recently published sham-controlled trials of high methodological quality confirm the safety and antihypertensive effectiveness of radiofrequency renal denervation. However, special clinical interest represents a suggestion that this type of treatment may improve hypertension-mediated organ damage. Purpose Comparative evaluation of renal denervation versus pharmacological treatment on diastolic function in patients with resistant hypertension. Methods The study enrolled 125 hypertensive patients who, following 4 weeks of standardized treatment with three antihypertensive remedies, one of which were a thiazide-like diuretic in maximum tolerated daily doses (Losartan, Amlodipine and Indapamid) and confirmation of their resistance, were randomly assigned into three groups depending on the treatment supplemented to the previously administered one: group I – Moxonidine, group II – Bisoprolol and group III – renal denervation (RDN). All patients were evaluated by transthoracic echocardiography at baseline, one, two and three years follow-up. A renal denervation was performed in the main renal arteries and their branches. Results At 1-year follow-up Bisoprolol and RDN treatment groups showed an authentic improvement in all diastolic function parameters, while Moxonidine group noted amelioration of only E/A ratio, LAVI and TR velocity. Two years of evaluation were marked by statistically significant changes of all diastolic parameters in all three observational groups. The improvement of diastolic function parameters continued until the end of the study, when the difference in dynamics between groups is evident thanks to the inferior effect of Moxonidine compared to Bisoprolol, RDN demonstrating superiority over both pharmacological treatment groups (Table 1). Conclusions Renal denervation demonstrated efficacy in improving of all parameters of diastolic function starting with 12 months of evaluation, the beneficial effect being maintained until the end of the surveillance period. At the same time, minimally invasive treatment has been shown to be superior to pharmacological treatment with SNS- blockers in improving diastolic function.

Abstract 13660: Endovascular Ultrasound Renal Denervation for Resistant Hypertension: A Systematic Review and Meta-Analysis of Randomized Sham-Controlled Trials

Background: Radiofrequency renal denervation (RDN) is used as a treatment for resistant hypertension, although its efficacy is still under evaluation. Similarly, ultrasound RDN, a less invasive technique, has yielded inconsistent results in this population. Hypothesis: Ultrasound RDN may lower blood pressure in patients with resistant hypertension. Aims: To compare the efficacy of ultrasound RDN versus a sham procedure in treating resistant hypertension. Methods: We systematically searched PubMed, Cochrane Library, and Embase in May 2023 to include randomized sham-controlled trials assessing the efficacy of ultrasound RDN. Statistical analyses were performed using Review Manager 5.4.1 using generic inverse variance weighting to pool mean ± standard deviation and least square mean ± standard error. Results: We included three studies comprising 323 patients with resistant hypertension on ≥ three antihypertensive medications, of whom 51.7% were randomized to RDN. Follow-up at analysis ranged from 8 to 24 weeks. There were no significant differences between groups in terms of change from baseline in 24-hour ambulatory systolic blood pressure (SBP; MD -2.15 mmHg; 95% -5.07, 0.76; p=0.15; Fig. 1A), 24-hour ambulatory diastolic blood pressure (DBP; MD -1.19 mmHg; 95% CI -2.91, 0.53; p=0.18; Fig. 1B) or office SBP (MD -1.71 mmHg; 95% CI -9.62, 6.20; p=0.67; Fig. 1C). Conclusion: In this meta-analysis, ultrasound RDN did not significantly reduce blood pressure in patients with resistant hypertension as compared with a sham procedure.

Abstract 13852: Sex Differences in Blood Pressure Reduction and Cardiovascular Outcomes in Patients With Resistant Hypertension Undergoing Radiofrequency Renal Denervation: Global SYMPLICITY Registry DEFINE

Introduction: Hypertension (HTN) prevalence and outcomes differ by sex. Radiofrequency renal denervation (RF RDN) safely reduces blood pressure (BP) in patients with resistant HTN. Hypothesis: After RF RDN, there are no sex-based differences in BP changes and cardiovascular (CV) outcomes. Methods: The Global SYMPLICITY Registry (GSR) DEFINE is an all-comer registry of patients with uncontrolled BP undergoing RF RDN. BP changes (analysis of covariance [ANCOVA] adjusted for baseline BP and age), CV death, stroke, myocardial infarction (MI) rates at 3yrs were compared between sexes with office systolic BP (OSBP) ≥140mmHg, prescribed ≥3 anti-HTN drugs. Results: Patients enrolled up to March 2023 were included (N=2502, female=1062). Females were older (62 vs 59 y; p&lt;0.0001), less likely to have a history of sleep apnea (12.5 vs 25.0% p&lt;0.0001), cardiac disease (45.2 vs 50.3%; p&lt;0.0012) and smoking (19.1 vs 41.3%; p&lt;0.0001). Body mass index, rates of diabetes and chronic kidney disease, number of anti-HTN drugs (5.1±1.5 in both sexes; p=0.88) and 24-hr SBP were similar by sex. Baseline OSBP was higher in females (174±23 vs 169±19mmHg; p&lt;0.0001). After 3yrs, OSBP significantly decreased in both sexes from baseline (female: -21.5mmHg vs male: -20.4mmHg; ANCOVA adjusted difference: 3.2mmHg [95% CI: 0.5 to 6.0; p=0.021]). There was no difference in 24-hr SBP change (Figure 1A) or number of anti-HTN drugs by sex. CV death rate was significantly higher in females (4.1% vs 2.1% vs p=0.024), but MI rate was significantly lower in females (1.3% vs 3.5%; p=0.007). Stroke rate was similar by sex (Figure 1). Conclusion: Females with resistant hypertension referred for RF RDN were older, had higher OSBP with fewer comorbidities compared to males. Despite similar BP reductions up to 3yrs after RF RDN, CV death rate in females was greater than males. These results suggest the need for sex specific analyses and control of HTN in females.

Long-term effectiveness of radiofrequency renal denervation in patients with resistant arterial hypertension (10-year follow-up results)

The aim – to determine the long-term efficacy and safety of renal denervation (RDN) at 10-year follow-up.Materials and methods. We selected 1146 patients with resistant arterial hypertension (RAH) who received 3 or more antihypertensive drugs. 16 patients were selected for renal artery denervation. RDN was performed in 8 patients (0.70 %). 8 patients refused the procedure. The age was 52.13 ± 3.88 years (40–66), the duration of hypertension was 16.75 ± 2.17 (12–25) years. The number of antihypertensive drugs was 5.5 ± 0.18. Office SBP/DBP on optimization of therapy in patients was 156.88/95.00 ± 2.98 mm Hg and heart rate – 68.88 ± 3.28 beats/min. 24SBP/DBP was 149.16 ± 5.40/86.98 ± 5.08 mm Hg. 24HR was 70.12 ± 2.94 beats/min. All patients tolerated the procedure well.Results and discussion. The decrease in office SBP/DBP was –12.59/–10.0 mm Hg; –11.17/–2.57 mm Hg; –20.31/–11.71 mm Hg, –27.71/–13.33 mm Hg and –30.21/–16.67 mm Hg, in the dynamics of 1 month, 12 months, 2 years, 5 years and 10 years, respectively, p &lt;0.05 for all values compared to the initial. The office heart rate at the stages of 1 month, 6, 12 months, 2 years, 5 and 10 years decreased, its dynamics were –3.74 bpm, –4.68 bpm, –1.45 bpm, –2.13 bpm, –4.21 bpm, –3.88 bpm, respectively. The decrease in 24SBP/DBP was –14.45/–6.95 mmHg, –8.70/–10.01 mm Hg, –19.45/–12.37 mm Hg, –19.91/–11.24 mm Hg, –29.93/–13.61 mm Hg. and –26.13/–23.35 mm Hg (p&lt;0.05 for all values). 24HR dynamics: –3.16 bpm, – 4.19 bpm, + 1.43 bpm, –1.51 bpm, –4.46 bpm, and –5.49 bpm, respectively. After 2, 5, and 10 years, all patients reached the target blood pressure level both in the office and with ABPM. Patients reduced the number of antihypertensive drugs from 5.50 ± 0.18 to 3.50 ± 0.30 – after 5 years and 3.67 ± 0.18 – after 10 years after RDN. GFR practically did not change over 10 years from 76.10 ± 5.62 to 64.60 ± 1.93 ml/min/1.73m2, p&gt;0.05. One patient died of thyroid cancer 2 years later. All other patients are alive and have not had any cardiovascular event or death during 10 years.Conclusion. Long-term results of renal artery denervation showed no cases of cardiovascular events, development of diabetes or cardiovascular death over 10 years. RDN contributed to a reduction in the number of antihypertensive drugs from 5.5 to 3.67 after 10 years of therapy against the background of 100 % achievement of the target BP level.

Abstract 056: Pooled, 6-month Renal Safety And Blood Pressure Reductions Using The Symplicity Spyral Radiofrequency Renal Denervation Catheter

Background: Renal denervation (RDN) targets the sympathetic nervous system to lower blood pressure (BP). Impact on long-term renal function after RDN is less well known. We report 6-month renal safety and BP reductions after RDN from the largest database, using the latest generation, multi-electrode, radiofrequency (RF) Symplicity Spyral™ catheter. Methods: A broad spectrum of patients with hypertension were enrolled in the SPYRAL HTN Global Clinical Program (4 major studies; SPYRAL First-In-Man, SPYRAL HTN-OFF MED, -ON MED and Global SYMPLICITY Registry [GSR]). GSR is an all-comer registry for patients with uncontrolled hypertension, including chronic kidney disease (CKD), whereas patients enrolled in the SPYRAL HTN-OFF and -ON MED trials required to have OSBP ≥150 and &lt;180 mmHg and ODBP ≥90 mmHg. OFF MED patients were required to have a drug washout period prior to treatment and did not take drugs for the first 3 months. ON MED patients were on a stable 1-3 antihypertensive drug regimen for 6 months. All were treated with RF RDN using the Spyral catheter. We pooled reductions in office and 24-h ambulatory BP, safety outcomes include changes in the estimated glomerular filtration rate (eGFR) and renal artery stenosis incidence (&gt;70%, confirmed by angiography). Results: As of December 2022, 1,284 patients have received RF RDN with the Spyral catheter. Patients at baseline were 58±12yrs old, 37.6% female, 29.1% had type 2 diabetes, eGFR was 77.7±23.9mL/min/1.73m2, 20.7% had CKD stage 3 or higher, OSBP was 166±21mmHg and ASBP was 153±16mmHg. 6 months after RDN, OSBP changed by -14.8±22.1 (n=940; p&lt;0.001) and ASBP changed by -8.9±16.0 (n=678; p&lt;0.001). Significant diastolic BP reductions were also observed. eGFR changed by -2.0mL/min/1.73m2. There was no incidence of renal artery stenosis (&gt;70%). Conclusion: In this large, pooled population of patients receiving RF RDN using the Spyral catheter, there were significant and consistent BP reductions through 6 months. There was no incidence of renal artery stenosis, and eGFR change was consistent with the natural progression of the aging hypertensive population. These data highlight the safety and efficacy of RF RDN as an adjunctive therapy to antihypertensive drugs to treat high BP.

Abstract P173: Impact Of Treatment Stage And Blood Pressure Severity On Preference For Drug And/or Device-based Treatments In Patients With Uncontrolled Hypertension

Background: Patient non-adherence to antihypertensive (AH) drugs impacts achieving treatment goals, highlighting the need for adjunctive therapies such as radiofrequency renal denervation (RDN). Patient preference for an intervention vs. drug therapy is poorly understood. We assessed patient treatment preferences at different stages of HTN management using a calculator derived from a discrete choice experiment (DCE) study. Methods: Preferences in 3 different clinical scenarios in the natural course of HTN management were evaluated: (1) initiating AH drugs vs. interventional treatment in untreated patients with mild-moderate HTN; (2) increasing drugs vs. interventional treatment with no drug change in patients with mild-moderate HTN; (3) increasing drugs vs. interventional treatment with no drug change in patients with severe resistant HTN. The predicted probability of choosing one treatment vs. the other was calculated based on preference-weighted treatment attributes (type of treatment, changes in AH drugs, BP reduction, effect duration, risk of drug side effects, intervention related adverse events). The values chosen for each scenario were derived from published RDN studies, the literature, and expert opinion. Results: Comparing scenario 1 to 2 to 3, the preference to select an intervention without drugs or change in drugs increased from 17% to 24% to 45%. Conversely, the preference to select either initiation or an increase in drugs decreased from 83% to 76% to 55%. The magnitude of BP reduction was the major driver of calculated patient preferences while drug and interventional treatment-related adverse events had a smaller impact on calculated patient preferences. Conclusions: Using preference-weights derived from a discrete choice experiment, a model predicting patient choice for drug vs. interventional treatment was applied to clinical scenarios derived from the natural course of management of patients with uncontrolled HTN. Preference for an interventional treatment increased from 17% in treatment naïve patients to 45% in patients with severe resistant HTN. Patient preference was driven predominantly by efficacy outcomes and minimally by safety concerns.

Cost-Effectiveness of Catheter-Based Radiofrequency Renal Denervation for the Treatment of Uncontrolled Hypertension: An Analysis for the UK Based on Recent Clinical Evidence

Cost-Effectiveness of Catheter-Based Radiofrequency Renal Denervation for the Treatment of Uncontrolled Hypertension: An Analysis for the UK Based on Recent Clinical Evidence

Outcomes Following Radiofrequency Renal Denervation According to Antihypertensive Medications: Subgroup Analysis of the Global SYMPLICITY Registry DEFINE.

The Global SYMPLICITY Registry DEFINE (Denervation Findings in Real World) investigates radiofrequency renal denervation (RDN) in a broad range of patients with hypertension. We evaluated whether the number or type of antihypertensive medications were associated with increased long-term blood pressure (BP) reductions and cardiovascular outcomes following radiofrequency RDN. Patients underwent radiofrequency RDN and were categorized by baseline number (0-3 and ≥4) and different combinations of medication classes. BP changes were compared between groups through 36 months. Individual and composite major adverse cardiovascular events were analyzed. Of 2746 evaluable patients, 18% were prescribed 0 to 3 and 82% prescribed ≥4 classes. At 36 months, office systolic BP significantly decreased (P<0.0001) by -19.0±28.3 and -16.2±28.6 mm Hg in the 0 to 3 and ≥4 class groups, respectively. Twenty-four-hour mean systolic BP significantly decreased (P<0.0001) by -10.7±19.7 and -8.9±20.5 mm Hg, respectively. BP reduction was similar between the medication subgroups. Antihypertensive medication classes decreased from 4.6±1.4 to 4.3±1.5 (P<0.0001). Most decreased (31%) or had no changes (47%) to the number of medications, while 22% increased. The number of baseline antihypertensive medication classes was inversely related to the change in prescribed classes at 36 months (P<0.001). Cardiovascular event rates were generally low. More patients in the ≥4 compared with 0 to 3 medication classes had myocardial infarction at 36 months (2.8% versus 0.3%; P=0.009). Radiofrequency RDN reduced BP safely through 36 months, independent of the number and type of baseline antihypertensive medication classes. More patients decreased than increased their number of medications. Radiofrequency RDN is a safe and effective adjunctive therapy regardless of antihypertensive medication regimen. URL: https://www. gov; Unique identifier: NCT01534299.

A PROSPECTIVE MULTICENTER RANDOMIZED SHAM-CONTROLLED CLINICAL TRIAL TO EVALUATE THE SAFETY AND EFFECTIVENESS OF NETRODTM RADIOFREQUENCY RENAL DENERVATION SYSTEM FOR HYPERTENSION

Objective: To evaluate the safety and effectiveness of a novel basket-like six-electrode radiofrequency renal denervation (RDN) system (NetrodTM RDN System) in treating patients with uncontrolled hypertension. Design and method: This is a prospective, multicenter, randomized sham-controlled trial. Patients with uncontrolled hypertension (office BP &gt; = 150/90 and &lt;180/110mmHg, and average SBP &gt; = 135mmHg by 24-hour ambulatory BP monitoring (ABPM), after taking &gt; = 2 antihypertensive drugs with stable dose for &gt; = 4 weeks) were screened after informed consent. All eligible patients first entered a lead-in period for &gt; = 4 weeks of standardized medication (Nifedipine + hydrochlorothiazide), and those continued to meet definition of uncontrolled hypertension were randomized 2:1 to RDN group (using NetrodTM RDN System) and sham control group (renal artery angiography only). All continued with the 2-drug regimen and were evaluated at 7 days or discharge (whichever comes first), 1, 2, 3 and 6 months post procedure. Both patients and site investigators who evaluate the patients were blinded to treatment assignment. The primary endpoint is office SBP change from baseline at 6 months post procedure. Secondary endpoints include changes from baseline of office DBP. 24-hour ABPM at 6 months post procedure and safety events. Results: A total of 205 patients from 25 centers were enrolled and 139 randomized to RDN group and 66 to sham control group, with no statistical difference of baseline clinical characteristics between the 2 groups including baseline BP. Compared to baseline, at 6 months post procedure RDN group has a significantly greater office SBP reduction than sham group (25.53 ± 12.62mmHg vs 8.39 ± 11.89mmHg, p &lt; 0.001). Office DBP change was -13.49 ± 8.09mmHg (RDN) vs -3.93 ± 9.04mmHg (sham), p &lt; 0.001. For 24-hour ABPM, the average SBP and DBP reduction were also significantly greater in the RDN vs sham group (11.91 ± 12.23 vs 3.87 ± 12.45mmHg, p &lt; 0.001; 6.03 ± 7.50 vs 1.68 ± 7.30mmHg, p &lt; 0.001, respectively). Device or procedure related serious adverse events were rare throughout the trial. Conclusions: The novel NetrodTM RDN System is safe and effective in treating uncontrolled hypertension with significant reduction in both office and 24-hour ambulatory BP.

PATIENT PREFERENCES IN PHARMACEUTICAL AND DEVICE-BASED TREATMENTS FOR UNCONTROLLED HYPERTENSION

Objective: Radiofrequency renal denervation (RDN) safely reduces high blood pressure (BP) in hypertensive (HTN) patients. Patient preference regarding such a treatment over antihypertensive (AH) drugs for uncontrolled HTN is poorly understood. Design and method: A recent discrete choice experiment (DCE) study in patients with uncontrolled HTN identified the reduction in systolic BP as the most important driver of patient preference between interventional treatments (e.g. RDN) or drugs. Using a predictive model consisting of the preference weights for safety and efficacy attributes from the DCE study, we calculated patients’ treatment preferences in 3 typical clinical scenarios in HTN management. Each scenario presented a choice to either initiate/increase AH drugs, or to have interventional treatment such as RDN: (1) AH drug naïve: initiate AH drugs vs. interventional treatment (2) mild-moderate HTN, 1-3 AH drugs: increasing AH drugs vs. intervention with no drug changes, (3) severe HTN (systolic BP &gt;150mmHg, &gt;3 AH drugs): increasing AH drugs vs. intervention with no drug changes. In each scenario, the average predicted probability of choosing one treatment over the other was calculated based on a benefit-risk profile from the sum of preference-weighted treatment attributes (type of treatment, changes in AH drugs, office systolic BP reducing efficacy, effect duration, risk of drug side effects, interventional treatment adverse events). Values of the treatment attributes were derived from the literature, expert opinion, and published RDN studies (SPYRAL HTN OFF-MED, ON-MED, Global SYMPLICITY Registry). Results: In (1), 17% preferred interventional treatment without drugs vs 83% preferred initiation of drugs. In (2), 24% preferred interventional treatment without increasing drugs vs 76% preferred increasing drugs. In (3), 45% preferred interventional treatment without increasing drugs vs 55% preferred increasing drugs. Preference differences were driven by the magnitude of office systolic BP reductions with each treatment. Risks of treatment-related adverse events were less important to treatment choices. Conclusions: Preference for RDN ranged from one-fifth to one-half of patients depending on clinical scenario. The increase mirrored the extent of prior treatment with AH drugs and HTN severity on drugs. Patient preference was driven predominantly by efficacy and minimally by safety of treatment.