Absence Of Antihypertensive Medications Research Articles

Efficacy and safety aspects of renal denervation in treatment of arterial hypertension: a systematic review and meta-analysis

Abstract Introduction Current guidelines for the management of arterial hypertension 2018 of European Society for Cardiology (ESC) do not recommend use of renal denervation (RDN) (as device-based therapy) for treatment of hypertension except as part of clinical studies. However, in the meantime several randomized sham-controlled clinical trials were designed using second generation radiofrequency (RF) (SPYRAL HTN-OFF MED, SPYRAL HTN-ON MED), ultrasound (RADIANCE-HTN SOLO, RADIANCE-HTN TRIO) or alcohol-mediated renal denervation (TARGET BP-OFF) devices. We aimed to perform a comprehensive meta-analysis from all published and unpublished randomized, sham-controlled clinical trials which explored the effects of renal denervation on blood pressure across different devices. Methods We searched MEDLINE and Embase via OVID@ for eligible trials. Of note, we also included unpublished data from the SPYRAL-ON Extension and TARGET BP OFF trials. Pooling the data from all studies, we explored the efficacy (ambulatory and office systolic and diastolic BP) and safety (all cause death, vascular complication, renal artery stenosis >70%, hypertensive crisis) of RDN. Results Analysis included 9 eligible trials (i.e. SYMPLICITY HTN-3, ReSET, SPYRAL HTN OFF MED, Desch et al., RADIANCE-HTN SOLO, RADIANCE-HTN TRIO, RADIANCE, TARGET BP OFF, SPYRAL HTN ON MED extension) comprising 2,091 patients (Table 1). RDN reduced ambulatory systolic (-3.10 mmHg, 95% CI -4.22, -1.97, p<0.00001) and office systolic (-5.15 mmHg, 95% CI -6.65, -3.66, p<0.00001) BP and ambulatory diastolic (-1.58 mmHg, 95% CI -2.54, -0.63, p=0.001) and office diastolic (-2.74 mmHg, 95% CI -3.65, -1.83, p<0.00001) BP compared with sham groups. There was no difference concerning ambulatory SBP reduction between trials with ON medication design (-2.94 mmHg, p<0.0001) and those with OFF medication design (-3.37 mmHg, p<0.0001) (p for interaction 0.69). Similarly, office SBP reduction was comparable between trials with (-4.38 mmHg, p<0.0001) and without concomitant antihypertensive drugs prescription (-6.27 mmHg, p<0.00001) (p for interaction 0.22). The rate of vascular complications (OR 1.21, 95% CI 0.28, 5.25, p=0.80), renal artery stenosis (OR 1.50, 95% CI 0.06, 36.97, p=0.80), hypertensive crisis (OR 1.39, 95% CI 0.50, 3.92, p=0.53) and all cause death (OR 0.52, 95% CI 0.10, 2.83, p=0.45) was not different between treatment and sham groups. Conclusions RDN is associated with clinically significant reductions in ambulatory and office SBP as compared with sham in the presence and absence of antihypertensive medication. The procedure use was not associated with an excess in safety events compared with sham group.

Safety and Efficacy of Renal Denervation in Patients Taking Antihypertensive Medications

BackgroundRenal denervation (RDN) reduces blood pressure (BP) in patients with uncontrolled hypertension in the absence of antihypertensive medications. ObjectivesThis trial assessed the safety and efficacy of RDN in the presence of antihypertensive medications. MethodsSPYRAL HTN-ON MED is a prospective, randomized, sham-controlled, patient- and assessor-blinded trial enrolling patients from 56 clinical centers worldwide. Patients were prescribed 1 to 3 antihypertensive medications. Patients were randomized to radiofrequency RDN or sham control procedure. The primary efficacy endpoint was the baseline-adjusted change in mean 24-hour ambulatory systolic BP at 6 months between groups using a Bayesian trial design and analysis. ResultsThe treatment difference in the mean 24-hour ambulatory systolic BP from baseline to 6 months between the RDN group (n = 206; −6.5 ± 10.7 mm Hg) and sham control group (n = 131; −4.5 ± 10.3 mm Hg) was −1.9 mm Hg (95% CI: −4.4 to 0.5 mm Hg; P = 0.12). There was no significant difference between groups in the primary efficacy analysis with a posterior probability of superiority of 0.51 (Bayesian treatment difference: −0.03 mm Hg [95% CI: −2.82 to 2.77 mm Hg]). However, there were changes and increases in medication intensity among sham control patients. RDN was associated with a reduction in office systolic BP compared with sham control at 6 months (adjusted treatment difference: −4.9 mm Hg; P = 0.0015). Night-time BP reductions and win ratio analysis also favored RDN. There was 1 adverse safety event among 253 assessed patients. ConclusionsThere was no significant difference between groups in the primary analysis. However, multiple secondary endpoint analyses favored RDN over sham control. (SPYRAL HTN-ON MED Study [Global Clinical Study of Renal Denervation With the Symplicity Spyral Multi-electrode Renal Denervation System in Patients With Uncontrolled Hypertension in the Absence of Antihypertensive Medications]; NCT02439775)

Safety and efficacy of renal sympathetic denervation: a 9-year long-term follow-up of 24-hour ambulatory blood pressure measurements.

Renal sympathetic denervation (RDN) has been shown to lower arterial blood pressure both in the presence and in the absence of antihypertensive medication in an observation period of up to 3 years. However, long-term results beyond 3 years are scarcely reported. We performed a long-term follow-up on patients who were previously enrolled in a local renal denervation registry and who underwent radiofrequency RDN with the Symplicity Flex® renal denervation system between 2011 and 2014. The patients were assessed to evaluate their renal function by performing 24-hour ambulatory blood pressure measurement (ABPM), recording their medical history, and conducting laboratory tests. Ambulatory blood pressure readings for 24 h were available for 72 patients at long-term follow-up (FU) [9.3 years (IQR: 8.5-10.1)]. We found a significant reduction of ABP from 150.1/86.1 ± 16.9/12.0 mmHg at baseline to 138.3/77.1 ± 16.5/11.1 mmHg at long-term FU (P < 0.001 for both systolic and diastolic ABP). The number of antihypertensive medications used by the patients significantly decreased from 5.4 ± 1.5 at baseline to 4.8 ± 1.6 at long-term FU (P < 0.01). Renal function showed a significant but expected age-associated decrease in the eGFR from 87.8 (IQR: 81.0-100.0) to 72.5 (IQR: 55.8-86.8) ml/min/1.73 m2 (P < 0.01) in patients with an initial eGFR > 60 ml/min/1.73 m2, while a non-significant decrease was observed in patients with an initial eGFR < 60 ml/min/1.73 m2 at long-term FU [56.0 (IQR: 40.9-58.4) vs. 39.0 (IQR: 13.5-56.3) ml/min/1.73 m2]. RDN was accompanied by a long-lasting reduction in blood pressure with a concomitant reduction in antihypertensive medication. No negative effects could be detected, especially with regard to renal function.

Endovascular Ultrasound Renal Denervation to Treat Hypertension

Two initial sham-controlled trials demonstrated that ultrasound renal denervation decreases blood pressure (BP) in patients with mild to moderate hypertension and hypertension that is resistant to treatment. To study the efficacy and safety of ultrasound renal denervation without the confounding influence of antihypertensive medications in patients with hypertension. Sham-controlled, randomized clinical trial with patients and outcome assessors blinded to treatment assignment that was conducted between January 14, 2019, and March 25, 2022, at 37 centers in the US and 24 centers in Europe, with randomization stratified by center. Patients aged 18 years to 75 years with hypertension (seated office systolic BP [SBP] ≥140 mm Hg and diastolic BP [DBP] ≥90 mm Hg despite taking up to 2 antihypertensive medications) were eligible if they had an ambulatory SBP/DBP of 135/85 mm Hg or greater and an SBP/DBP less than 170/105 mm Hg after a 4-week washout of their medications. Patients with an estimated glomerular filtration rate of 40 mL/min/1.73 m2 or greater and with suitable renal artery anatomy were randomized 2:1 to undergo ultrasound renal denervation or a sham procedure. Patients were to abstain from antihypertensive medications until the 2-month follow-up unless prespecified BP criteria were exceeded and were associated with clinical symptoms. Ultrasound renal denervation vs a sham procedure. The primary efficacy outcome was the mean change in daytime ambulatory SBP at 2 months. The primary safety composite outcome of major adverse events included death, kidney failure, and major embolic, vascular, cardiovascular, cerebrovascular, and hypertensive events at 30 days and renal artery stenosis greater than 70% detected at 6 months. The secondary outcomes included mean change in 24-hour ambulatory SBP, home SBP, office SBP, and all DBP parameters at 2 months. Among 1038 eligible patients, 150 were randomized to ultrasound renal denervation and 74 to a sham procedure (mean age, 55 years [SD, 9.3 years]; 28.6% female; and 16.1% self-identified as Black or African American). The reduction in daytime ambulatory SBP was greater with ultrasound renal denervation (mean, -7.9 mm Hg [SD, 11.6 mm Hg]) vs the sham procedure (mean, -1.8 mm Hg [SD, 9.5 mm Hg]) (baseline-adjusted between-group difference, -6.3 mm Hg [95% CI, -9.3 to -3.2 mm Hg], P < .001), with a consistent effect of ultrasound renal denervation throughout the 24-hour circadian cycle. Among 7 secondary BP outcomes, 6 were significantly improved with ultrasound renal denervation vs the sham procedure. No major adverse events were reported in either group. In patients with hypertension, ultrasound renal denervation reduced daytime ambulatory SBP at 2 months in the absence of antihypertensive medications vs a sham procedure without postprocedural major adverse events. ClinicalTrials.gov Identifier: NCT03614260.

JS-HR-10: ADVANCES IN RENAL DENERVATION FOR TREATING HYPERTENSION

Excessive activation of sympathetic nervous system is closely related to the onset and progression of hypertension. Renal nerves are composed of sympathetic efferent and sensory afferent nerves. Activation of the efferent renal sympathetic nerves induces renin secretion, sodium absorption, and increased renal vascular resistance, which lead to increased blood pressure (BP) and fluid retention. Afferent renal sensory nerves, which are densely innervated in the renal pelvic wall, project to the cardiovascular center in the brain to modulate sympathetic outflow to the periphery, including the heart, kidneys, and arterioles. Renal denervation (RDN) is a neuromodulation therapy that partially interrupts both the efferent outputs from the brain to the kidney and the afferent inputs from the kidney to the brain and has attracted attention as a novel device therapy for hypertension. In clinical practice, denervation is performed through the lumen of the renal artery using a catheter. Radiofrequency, ultrasound, and alcohol-based RDN devices are being developed as new second-generation devices. A randomized sham-controlled trials using 24-hour ambulatory BP measurement is required for approval of clinical use of RDN. The SPYRAL HTN OFF-MED pivotal trial showed the superiority of RDN using radiofrequency-based catheter compared with a sham procedure to safely lower 24-hour systolic BP in the absence of antihypertensive medications. The RADIANCE-HTN TRIO trials showed the superiority of RDN using ultrasound-based catheter compared with a sham procedure to safely lower daytime BP in patients with resistant hypertension. The REQUIRE trial is the first trial of ultrasound RDN in Asian patients from Japan and South Korea with resistant hypertension. The study findings were neutral for the primary endpoint, with similar reductions in 24-hour systolic BP in the RDN and sham control groups. Although BP reduction after RDN was similar to other sham-controlled studies, the sham group in this study showed much greater reduction. Japanese Society of Hypertension performed the meta-analysis of nine randomized sham-controlled trials of RDN including these three trials mentioned above. The results showed that RDN significantly reduced a range of office, home and 24-hour BP parameters in patients with resistant, uncontrolled, and drug-naïve hypertension. There were no significant differences in magnitude of BP reduction between radiofrequency-based and ultrasound-based devices. Recently, the efficacy and safety of RDN in the SPYRAL HTN OFF-MED pivotal trial up to 36 months have been reported. In this session, the latest basic and clinical evidence/aspects of RDN will be summarized and discussed, which is about to be introduced into the clinical practice.

Hypertension urgencies in the SPYRAL HTN-OFF MED Pivotal trial

The SPYRAL HTN-OFF MED Pivotal trial (https://clinicaltrials.gov/ct2/show/NCT02439749) demonstrated significant reductions in blood pressure (BP) after renal denervation (RDN) compared to sham control in the absence of anti-hypertensive medications. Prior to the 3-month primary endpoint, medications were immediately reinstated for patients who met escape criteria defined as office systolic BP (SBP) ≥ 180 mmHg or other safety concerns. Our objective was to compare the rate of hypertensive urgencies in RDN vs. sham control patients. Patients were enrolled with office SBP ≥ 150 and < 180 mmHg, office diastolic BP (DBP) ≥ 90 mmHg and mean 24 h SBP ≥ 140 and < 170 mmHg. Patients had been required to discontinue any anti-hypertensive medications and were randomized 1:1 to RDN or sham control. In this post-hoc analysis, cumulative incidence curves with Kaplan–Meier estimates of rate of patients meeting escape criteria were generated for RDN and sham control patients. There were 16 RDN (9.6%) and 28 sham control patients (17.0%) who met escape criteria between baseline and 3 months. There was a significantly higher rate of sham control patients meeting escape criteria compared to RDN for all escape patients (p = 0.032), as well as for patients with a hypertensive urgency with office SBP ≥ 180 mmHg (p = 0.046). Rate of escape was similar between RDN and sham control for patients without a measured BP exceeding 180 mmHg (p = 0.32). In the SPYRAL HTN-OFF MED Pivotal trial, RDN patients were less likely to experience hypertensive urgencies that required immediate use of anti-hypertensive medications compared to sham control.Graphical abstract

Abordagem Fisioterapêutica Na Hipertensão Arterial Sistêmica

Hypertension (AH) is a chronic non-communicable disease (NCD) defined by blood pressure levels, in which the benefits of treatment (non-medication and/or medication) outweigh the risks. It is a multifactorial condition, which depends on genetic/epigenetic, environmental and social factors, characterized by persistent elevation of blood pressure (BP), that is, systolic BP (SBP) greater than or equal to 140 mmHg and/or diastolic BP (DBP) greater than or equal to 90 mmHg, measured with the correct technique, on at least two different occasions, in the absence of antihypertensive medication. In 2021, a systematic search of the scientific literature of the main biomedical databases was carried out: Scielo, BVS, MEDLINE and Brazilian Guidelines on Hypertension between the years 2007 to 2021, aiming at the importance of physical therapy as a therapeutic in the control and treatment of SAH. It is evident that even today many difficulties are encountered to establish a 100% effective project for the prevention of SAH, but the role of physical activity in prevention and treatment, light and moderate intensity exercises, from two to three times, is notorious. in the week they were more effective, providing an improvement in the quality of life of these patients. &nbsp;

Effect of Heart Rate on the Outcome of Renal Denervation in Patients With Uncontrolled Hypertension

BackgroundSham-controlled trials demonstrated safety and efficacy of renal denervation (RDN) to lower blood pressure (BP). Association of baseline heart rate with BP reduction after RDN is incompletely understood. ObjectivesThe purpose of this analysis was to evaluate the impact of baseline heart rate on BP reduction without antihypertensive medications in the SPYRAL HTN-OFF MED (Global Clinical Study of Renal Denervation With the Symplicity Spyral Multi-electrode Renal Denervation System in Patients With Uncontrolled Hypertension in the Absence of Antihypertensive Medications) Pivotal trial. MethodsPatients removed from any antihypertensive medications were enrolled with office systolic blood pressure (SBP) ≥150 and <180 mm Hg and randomized 1:1 to RDN or sham control. Patients were separated according to baseline office heart rate <70 or ≥70 beats/min. BP changes from baseline to 3 months between treatment arms were adjusted for baseline SBP using analysis of covariance. ResultsScatter plots of 3-month changes in 24-hour and office SBP illustrate a wide range of changes in SBP for different baseline heart rates. Treatment difference at 3 months between RDN and sham control with baseline office heart rate ≥70 beats/min for 24-hour SBP was −6.2 mm Hg (95% CI: −9.0 to −3.5 mm Hg) (P < 0.001) and for baseline office heart rate <70 beats/min it was −0.1 mm Hg (−3.8 to 3.6 mm Hg) (P = 0.97) with an interaction P value of 0.008. Results were similar for changes in office, daytime, and nighttime SBP at 3 months, with a greater reduction in SBP with baseline office heart rate ≥70 beats/min. ConclusionsReduction in mean office, 24-hour, daytime, and nighttime SBP for RDN at 3 months was greater with baseline office heart rate ≥70 than <70 beats/min, suggesting an association between baseline heart rate and BP reduction after RDN. (SPYRAL PIVOTAL—SPYRAL HTN-OFF MED Study; NCT02439749)

Efficacy of a digital therapeutics system in the management of essential hypertension: the HERB-DH1 pivotal trial.

AimsDigital therapeutics is a new approach to facilitate the non-pharmacological treatment of hypertension using software programmes such as smartphone applications and/or device algorithms. Based on promising findings from a small pilot trial, the HERB Digital Hypertension 1 (HERB-DH1) pivotal trial investigated the efficacy of digital therapeutics in patients with hypertension not receiving antihypertensive medication.Methods and resultsThis prospective, open-label, randomized controlled study was performed at 12 sites in Japan. Patients with hypertension [office systolic blood pressure (SBP) 140 to <180 mmHg and 24 h SBP ≥130 mmHg] were randomly assigned 1:1 to the digital therapeutics group (HERB system + standard lifestyle modification) or control group (standard lifestyle modification alone). The primary efficacy endpoint was the mean change in 24 h ambulatory SBP from baseline to 12 weeks; key secondary efficacy endpoints were mean changes in office and home blood pressure (BP) from baseline to 12 weeks. All analyses were conducted in the full analysis set population. Between December 2019 and June 2020, 390 patients were randomly assigned to the digital therapeutics group (n = 199) or control (n = 191) group. Between-group differences in 24-h ambulatory, home, and office SBPs at 12 weeks were −2.4 (95% confidence interval −4.5 to −0.3), −4.3 (−6.7 to −1.9), and −3.6 (−6.2 to −1.0) mmHg, respectively. No major programme-related safety events occurred up to 24 weeks.ConclusionThe HERB-DH1 pivotal study showed the superiority of digital therapeutics compared with standard lifestyle modification alone to reduce 24-h ambulatory, home, and office BPs in the absence of antihypertensive medications.

Catheter-based alcohol-mediated renal denervation for the treatment of uncontrolled hypertension: design of two sham-controlled, randomized, blinded trials in the absence (TARGET BP OFF-MED) and presence (TARGET BP I) of antihypertensive medications

Arterial hypertension is a common and life-threatening condition and poses a large global health burden. Device-based treatments have been developed as adjunctive or alternative therapy, to be used with or without antihypertensive medication for treating uncontrolled hypertension. The safety and feasibility of chemical renal denervation (RDN) using the Peregrine Catheter and alcohol were demonstrated in a first-in-man and open-label clinical trials, prompting the initiation of the ongoing TARGET BP OFF-MED and TARGET BP I trials. The TARGET BP trials are randomized, blinded, sham-controlled trials designed to assess the safety and efficacy of alcohol-mediated RDN for the treatment of uncontrolled hypertension in the absence of antihypertensive medications (TARGET BP OFF-MED) or in addition to prescribed antihypertensive medications (TARGET BP I). Subjects with confirmed uncontrolled hypertension and suitable renal artery anatomy are randomized (1:1) to receive either RDN using the Peregrine Kit with alcohol (0.6mL per renal artery) infused through the Peregrine Catheter or diagnostic renal angiography only (sham procedure). TARGET BP OFF-MED completed enrollment and randomized 96 subjects. TARGET BP I will randomize approximately 300 subjects and will transition to an open-label safety cohort of approximately 300 subjects receiving RDN once the primary efficacy endpoint of the Randomized Controlled Trial (RCT) cohort has been met. Primary endpoints are change in mean 24-hour ambulatory systolic blood pressure from baseline to 8 weeks (TARGET BP OFF-MED) and 3months (TARGET BP I) post-procedure. The TARGET BP trials are the first large-scale, international, randomized trials aimed to investigate the safety and BP lowering efficacy of a novel RDN method, with perivascular alcohol delivery using the Peregrine Kit.

Blood pressure and renal denervation with ultrasound: another step forward

Among cardiovascular risk factors, arterial hypertension has the highest prevalence and is poorly controlled. 1 Stanaway JD Afshin A Gakidou E et al. Global, regional, and national comparative risk assessment of 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks for 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet. 2018; 392: 1923-1994 Summary Full Text Full Text PDF PubMed Scopus (1438) Google Scholar The sympathetic nervous system targeting the kidney via efferent and afferent nerves, thereby contributing to hypertension and potentially other cardiovascular conditions, 2 Böhm M Linz D Ukena C Esler M Mahfoud F Renal denervation for the treatment of cardiovascular high risk-hypertension or beyond?. Circ Res. 2014; 115: 400-409 Crossref PubMed Scopus (62) Google Scholar can be modulated with different denervation technologies. 3 Lauder L Azizi M Kirtane AJ Böhm M Mahfoud F Device-based therapies for arterial hypertension. Nat Rev Cardiol. 2020; 17: 614-628 Crossref PubMed Scopus (17) Google Scholar Rigorously controlled clinical trials without 4 Böhm M Townsend RR Kario K et al. Rationale and design of two randomized sham-controlled trials of catheter-based renal denervation in subjects with uncontrolled hypertension in the absence (SPYRAL HTN-OFF MED Pivotal) and presence (SPYRAL HTN-ON MED Expansion) of antihypertensive medications: a novel approach using Bayesian design. Clin Res Cardiol. 2020; 109: 289-302 PubMed Google Scholar , 5 Böhm M Kario K Kandzari DE et al. Efficacy of catheter-based renal denervation in the absence of antihypertensive medications (SPYRAL HTN-OFF MED Pivotal): a multicentre, randomised, sham-controlled trial. Lancet. 2020; 395: 1444-1451 Summary Full Text Full Text PDF PubMed Scopus (102) Google Scholar , 6 Townsend RR Mahfoud F Kandzari DE et al. Catheter-based renal denervation in patients with uncontrolled hypertension in the absence of antihypertensive medications (SPYRAL HTN-OFF MED): a randomised, sham-controlled, proof-of-concept trial. Lancet. 2017; 390: 2160-2170 Summary Full Text Full Text PDF PubMed Scopus (374) Google Scholar and with 7 Kandzari DE Böhm M Mahfoud F et al. Effect of renal denervation on blood pressure in the presence of antihypertensive drugs: 6-month efficacy and safety results from the SPYRAL HTN-ON MED proof-of-concept randomised trial. Lancet. 2018; 391: 2346-2355 Summary Full Text Full Text PDF PubMed Scopus (302) Google Scholar antihypertensive medications have shown a significant reduction in blood pressure with high-frequency energy. Ultrasound renal denervation for hypertension resistant to a triple medication pill (RADIANCE-HTN TRIO): a randomised, multicentre, single-blind, sham-controlled trialCompared with a sham procedure, ultrasound renal denervation reduced blood pressure at 2 months in patients with hypertension resistant to a standardised triple combination pill. If the blood pressure lowering effect and safety of renal denervation are maintained in the long term, renal denervation might be an alternative to the addition of further antihypertensive medications in patients with resistant hypertension. Full-Text PDF

Device-based therapies for arterial hypertension.

Arterial hypertension is the most prevalent modifiable risk factor associated with cardiovascular morbidity and mortality. Although antihypertensive drugs are widely available, in many patients blood pressure control to guideline-recommended target values is not achieved. Several device-based approaches have been introduced to lower blood pressure; most of these strategies aim to modulate autonomic nervous system activity. Clinical trials have moved from including patients with resistant hypertension receiving intensive pharmacological treatment to including patients with mild-to-moderate hypertension in the presence or absence of antihypertensive medications. Renal sympathetic denervation is the most extensively investigated device-based therapy for hypertension, and randomized, sham-controlled trials have provided proof-of-principle data for its blood pressure-lowering efficacy. Unilateral electrical baroreflex activation, endovascular baroreflex amplification and pacemaker-mediated cardiac neuromodulation therapy have yielded promising results in observational trials, which need to be confirmed in larger, adequately powered, sham-controlled trials. Until further evidence becomes available, device-based therapy for hypertension should not be considered for routine treatment. However, when considering a device-based treatment for hypertension, the underlying pathophysiology in each patient has to be taken into consideration, and the procedural risks weighed against the cardiovascular risk attributable to the elevated blood pressure. This Review summarizes the pathophysiological rationale and the latest clinical evidence for device-based therapies for hypertension.

Efficacy of catheter-based renal denervation in the absence of antihypertensive medications (SPYRAL HTN-OFF MED Pivotal): a multicentre, randomised, sham-controlled trial

Catheter-based renal denervation has significantly reduced blood pressure in previous studies. Following a positive pilot trial, the SPYRAL HTN-OFF MED (SPYRAL Pivotal) trial was designed to assess the efficacy of renal denervation in the absence of antihypertensive medications. In this international, prospective, single-blinded, sham-controlled trial, done at 44 study sites in Australia, Austria, Canada, Germany, Greece, Ireland, Japan, the UK, and the USA, hypertensive patients with office systolic blood pressure of 150 mm Hg to less than 180 mm Hg were randomly assigned 1:1 to either a renal denervation or sham procedure. The primary efficacy endpoint was baseline-adjusted change in 24-h systolic blood pressure and the secondary efficacy endpoint was baseline-adjusted change in office systolic blood pressure from baseline to 3 months after the procedure. We used a Bayesian design with an informative prior, so the primary analysis combines evidence from the pilot and Pivotal trials. The primary efficacy and safety analyses were done in the intention-to-treat population. This trial is registered at ClinicalTrials.gov, NCT02439749. From June 25, 2015, to Oct 15, 2019, 331 patients were randomly assigned to either renal denervation (n=166) or a sham procedure (n=165). The primary and secondary efficacy endpoints were met, with posterior probability of superiority more than 0·999 for both. The treatment difference between the two groups for 24-h systolic blood pressure was -3·9 mm Hg (Bayesian 95% credible interval -6·2 to -1·6) and for office systolic blood pressure the difference was -6·5 mm Hg (-9·6 to -3·5). No major device-related or procedural-related safety events occurred up to 3 months. SPYRAL Pivotal showed the superiority of catheter-based renal denervation compared with a sham procedure to safely lower blood pressure in the absence of antihypertensive medications. Medtronic.

Abstract 109: Changes in Plasma Renin Activity After Renal Denervation in the Spyral Htn-Off Med Trial

Results from recent sham-controlled clinical trials demonstrate the efficacy of renal denervation (RDN) in blood pressure reduction, however the effects of RDN on the renin-angiotensin system are not clear. We sought to evaluate changes in plasma renin activity (PRA) and serum sodium levels after RDN in the absence of anti-hypertensive medications in the SPYRAL HTN-OFF MED trial. SPYRAL HTN-OFF MED is a randomized, sham-controlled trial to evaluate the impact of RDN in the absence of anti-hypertensive medications. Patients were enrolled with an office systolic BP (SBP) ≥150 and &lt;180 mmHg, office diastolic BP ≥90 mmHg, and a mean 24-hour SBP ≥140 and &lt;170 mmHg. Patients were randomized 1:1 to RDN with the SYMPLICITY Spyral™ catheter (N=38) or sham procedure (N=42). PRA and serum sodium levels were measured at baseline and 3 months post-procedure. Changes were expressed using medians and interquartile ranges and compared between groups using the Mann-Whitney U-test. Change in PRA from baseline to 3 months was significantly greater for the RDN group (n=23) -0.15 ng/mL/h [-0.76, -0.02] compared to the sham control group (n=33) 0.02 ng/mL/h [-0.16, 0.16]; p=0.018 ( Figure ). Comparison of 3-month changes in PRA using a Wilcoxon test stratified by 3 equal groups of baseline PRA also found a significant difference between groups (p=0.033). Changes in sodium levels were similar between groups: 0 mmol/L [-2, 2] (RDN, N=37) vs. 0 mmol/L [-1, 1] (control, N=41), p=0.920). In this sham-controlled feasibility trial, renal denervation was associated with a reduction in PRA but no difference in serum sodium levels was observed. The impact on sodium excretion will need to be assessed in future studies.

Safety and Efficacy of a New Renal Denervation Catheter in Hypertensive Patients in the Absent of Antihypertensive Medications: A Pilot Study.

Aim The aim of present study was to determine the safety and efficacy of a new renal artery denervation system for treatment of hypertensive patients. Methods Hypertensive patients with mean office systolic blood pressure ≥150mmHg and ≤180mmHg or an average of 24-hour ambulatory systolic blood pressure ≥145mmHg and ≤170mmHg after stopping hypertensive medications for 2 weeks or more were enrolled to undergo renal denervation (RDN) using a new RDN system. Changes in office blood pressure and mean 24-hour ambulatory blood pressure and safety were assessed after 6 months. Results Fifteen patients underwent RDN and followed up for 6 months. At the 6-month follow-up, office systolic blood pressure decreased 11.5±9.9mmHg (P<0.01) and office diastolic blood pressure decreased 6.9±4.8mmHg (P<0.01); mean 24-hour ambulatory systolic blood pressure decreased 7.5±7.7mmHg (P<0.05) and mean 24-hour diastolic blood pressure decreased 3.3±4.7mmHg (P>0.05) compared to baseline values. There were no serious RDN-related adverse events during follow-up. Conclusion Our results demonstrate that the new RDN system is safe and could significantly reduce blood pressure in hypertensive patients in the absence of antihypertensive medications. This trial is registered with ChiCTR1800017815.

Will SPYRAL HTN-OFF MED change my practice? SPYRAL HTN-OFF MED: a prospective, randomised, sham-controlled trial on renal denervation in the absence of antihypertensive medications.

Will SPYRAL HTN-OFF MED change my practice? SPYRAL HTN-OFF MED: a prospective, randomised, sham-controlled trial on renal denervation in the absence of antihypertensive medications.

Endovascular ultrasound renal denervation to treat hypertension (RADIANCE-HTN SOLO): a multicentre, international, single-blind, randomised, sham-controlled trial

Early studies suggest that radiofrequency-based renal denervation reduces blood pressure in patients with moderate hypertension. We investigated whether an alternative technology using endovascular ultrasound renal denervation reduces ambulatory blood pressure in patients with hypertension in the absence of antihypertensive medications. RADIANCE-HTN SOLO was a multicentre, international, single-blind, randomised, sham-controlled trial done at 21 centres in the USA and 18 in Europe. Patients with combined systolic-diastolic hypertension aged 18-75 years were eligible if they had ambulatory blood pressure greater than or equal to 135/85 mm Hg and less than 170/105 mm Hg after a 4-week discontinuation of up to two antihypertensive medications and had suitable renal artery anatomy. Patients were randomised (1:1) to undergo renal denervation with the Paradise system (ReCor Medical, Palo Alto, CA, USA) or a sham procedure consisting of renal angiography only. The randomisation sequence was computer generated and stratified by centres with randomised blocks of four or six and permutation of treatments within each block. Patients and outcome assessors were blinded to randomisation. The primary effectiveness endpoint was the change in daytime ambulatory systolic blood pressure at 2 months in the intention-to-treat population. Patients were to remain off antihypertensive medications throughout the 2 months of follow-up unless specified blood pressure criteria were exceeded. Major adverse events included all-cause mortality, renal failure, an embolic event with end-organ damage, renal artery or other major vascular complications requiring intervention, or admission to hospital for hypertensive crisis within 30 days and new renal artery stenosis within 6 months. This study is registered with ClinicalTrials.gov, number NCT02649426. Between March 28, 2016, and Dec 28, 2017, 803 patients were screened for eligibility and 146 were randomised to undergo renal denervation (n=74) or a sham procedure (n=72). The reduction in daytime ambulatory systolic blood pressure was greater with renal denervation (-8·5 mm Hg, SD 9·3) than with the sham procedure (-2·2 mm Hg, SD 10·0; baseline-adjusted difference between groups: -6·3 mm Hg, 95% CI -9·4 to -3·1, p=0·0001). No major adverse events were reported in either group. Compared with a sham procedure, endovascular ultrasound renal denervation reduced ambulatory blood pressure at 2 months in patients with combined systolic-diastolic hypertension in the absence of medications. ReCor Medical.

Renal Denervation: Paradise Lost? Paradise Regained?

Renal denervation is a relatively recent concept whose initial promising results suffered a setback following the SYMPLICITY 3 trial, which did not show a significant blood pressure-lowering effect in comparison to sham. In this review article, we begin with the history including the physiological basis behind the concept of renal denervation. Furthermore, we review the literature in support of renal denervation, including the recently published SPYRAL HTN-OFF MED, which demonstrated significant blood pressure reduction in the absence of antihypertensive medication. We further touch upon the potential pitfalls and possible future directions of renal denervation.

Catheter-based renal denervation in patients with uncontrolled hypertension in the absence of antihypertensive medications (SPYRAL HTN-OFF MED): a randomised, sham-controlled, proof-of-concept trial

Previous randomised renal denervation studies did not show consistent efficacy in reducing blood pressure. The objective of our study was to evaluate the effect of renal denervation on blood pressure in the absence of antihypertensive medications. SPYRAL HTN-OFF MED was a multicentre, international, single-blind, randomised, sham-controlled, proof-of-concept trial. Patients were enrolled at 21 centres in the USA, Europe, Japan, and Australia. Eligible patients were drug-naive or discontinued their antihypertensive medications. Patients with an office systolic blood pressure (SBP) of 150 mm Hg or greater and less than 180 mm Hg, office diastolic blood pressure (DBP) of 90 mm Hg or greater, and a mean 24-h ambulatory SBP of 140 mm Hg or greater and less than 170 mm Hg at second screening underwent renal angiography and were randomly assigned to renal denervation or sham control. Patients, caregivers, and those assessing blood pressure were blinded to randomisation assignments. The primary endpoint, change in 24-h blood pressure at 3 months, was compared between groups. Drug surveillance was done to ensure patient compliance with absence of antihypertensive medication. The primary analysis was done in the intention-to-treat population. Safety events were assessed at 3 months. This study is registered with ClinicalTrials.gov, number NCT02439749. Between June 25, 2015, and Jan 30, 2017, 353 patients were screened. 80 patients were randomly assigned to renal denervation (n=38) or sham control (n=42) and followed up for 3 months. Office and 24-h ambulatory blood pressure decreased significantly from baseline to 3 months in the renal denervation group: 24-h SBP -5·5 mm Hg (95% CI -9·1 to -2·0; p=0·0031), 24-h DBP -4·8 mm Hg (-7·0 to -2·6; p<0·0001), office SBP -10·0 mm Hg (-15·1 to -4·9; p=0·0004), and office DBP -5·3 mm Hg (-7·8 to -2·7; p=0·0002). No significant changes were seen in the sham-control group: 24-h SBP -0·5 mm Hg (95% CI -3·9 to 2·9; p=0·7644), 24-h DBP -0·4 mm Hg (-2·2 to 1·4; p=0·6448), office SBP -2·3 mm Hg (-6·1 to 1·6; p=0·2381), and office DBP -0·3 mm Hg (-2·9 to 2·2; p=0·8052). The mean difference between the groups favoured renal denervation for 3-month change in both office and 24-h blood pressure from baseline: 24-h SBP -5·0 mm Hg (95% CI -9·9 to -0·2; p=0·0414), 24-h DBP -4·4 mm Hg (-7·2 to -1·6; p=0·0024), office SBP -7·7 mm Hg (-14·0 to -1·5; p=0·0155), and office DBP -4·9 mm Hg (-8·5 to -1·4; p=0·0077). Baseline-adjusted analyses showed similar findings. There were no major adverse events in either group. Results from SPYRAL HTN-OFF MED provide biological proof of principle for the blood-pressure-lowering efficacy of renal denervation. Medtronic.

Masked Hypertension and Morning Blood Pressure Surge in Patients with Obstructive Sleep Apnea Syndrome

Objective: Frequent hypoxic episodes and arousal during sleep in obstructive sleep apnea syndrome (OSAS) result in increased nocturnal blood pressure, which in turn may lead to sustained hypertension. Patients with severe OSAS exhibit attenuated nocturnal blood pressure (BP) dipping, as well as marked and rapid BP elevation in the morning shortly after waking. We examined the prevalence of masked hypertension and morning BP surge in patients with OSAS, and the relationship between the severity of OSAS and abnormal circadian BP patterns. Methods: We performed 24-hour ambulatory BP monitoring in the absence of antihypertensive medication on 26 patients with OSAS (49.3 ± 8.4 yrs) to investigate masked hypertension and morning BP surge. Results: Results of the 26 patients, three (11.7%) were normotensive, six (23.0%) exhibited masked hypertension, and 17 (65.3%) were hypertensive. The apnea/hypopnea index was significantly correlated with 24-hour mean, daytime, and night time systolic and diastolic BP. 24-hour mean, daytime, and night time BPs in the severe OSAS group were significantly higher than in the mild to moderate OSAS group. We observed morning BP surge in 16 patients (61.5%). There were no significant differences in the prevalence of morning BP surge and masked hypertension between the mild to moderate and the severe OSAS groups. Conclusion: Mild to moderate OSAS may play an important role in masked hypertension and morning BP surge.