Search

Background: The randomized, sham-controlled RADIANCE-HTN (A Study of the Recor Medical Paradise System in Clinical Hypertension) SOLO, RADIANCE-HTN TRIO, and RADIANCE II (A Study of the Recor Medical Paradise System in Stage II Hypertension) trials independently met their primary end point of a greater reduction in daytime ambulatory systolic blood pressure (SBP) 2 months after ultrasound renal denervation (uRDN) in patients with hypertension. To characterize the longer-term effectiveness and safety of uRDN versus sham at 6 months, after the blinded addition of antihypertensive treatments (AHTs), we pooled individual patient data across these 3 similarly designed trials., Methods: Patients with mild to moderate hypertension who were not on AHT or with hypertension resistant to a standardized combination triple AHT were randomized to uRDN (n=293) versus sham (n=213); they were to remain off of added AHT throughout 2 months of follow-up unless specified blood pressure (BP) criteria were exceeded. In each trial, if monthly home BP was ≥135/85 mm Hg from 2 to 5 months, standardized AHT was sequentially added to target home BP <135/85 mm Hg under blinding to initial treatment assignment. Six-month outcomes included baseline- and AHT-adjusted change in daytime ambulatory, home, and office SBP; change in AHT; and safety. Linear mixed regression models using all BP measurements and change in AHT from baseline through 6 months were used., Results: Patients (70% men) were 54.1±9.3 years of age with a baseline daytime ambulatory/home/office SBP of 150.5±9.8/151.0±12.4/155.5±14.4 mm Hg, respectively. From 2 to 6 months, BP decreased in both groups with AHT titration, but fewer uRDN patients were prescribed AHT ( P =0.004), and fewer additional AHT were prescribed to uRDN patients versus sham patients ( P =0.001). Whereas the unadjusted between-group difference in daytime ambulatory SBP was similar at 6 months, the baseline and medication-adjusted between-group difference at 6 months was -3.0 mm Hg (95% CI, -5.7, -0.2; P =0.033), in favor of uRDN+AHT. For home and office SBP, the adjusted between-group differences in favor of uRDN+AHT over 6 months were -5.4 mm Hg (-6.8, -4.0; P <0.001) and -5.2 mm Hg (-7.1, -3.3; P <0.001), respectively. There was no heterogeneity between trials. Safety outcomes were few and did not differ between groups., Conclusions: This individual patient-data analysis of 506 patients included in the RADIANCE trials demonstrates the maintenance of BP-lowering efficacy of uRDN versus sham at 6 months, with fewer added AHTs., Registration: URL: https://www.clinicaltrials.gov; Unique identifiers: NCT02649426 and NCT03614260., Competing Interests: Disclosures Dr Azizi reports receiving grants from the European Horizon 2020 program; grants and nonfinancial support from Recor Medical, Idorsia, and Novartis; and personal fees from Alnylam Pharmaceuticals, Cincor, Medtronic, AstraZeneca, and Novartis. Dr Sharp has received personal fees from Recor Medical, Medtronic, Boston Scientific, Penumbra, and Philips. Dr Fisher has received grant support and personal fees from Recor Medical and personal fees from Medtronic. Dr Lobo has received personal fees from Recor Medical, Medtronic, Ablative Solutions, and Vascular Dynamics; and has received grants from Medtronic. Dr Daemen received institutional grant or research support from Abbott Vascular, Boston Scientific, ACIST Medical, Medtronic, Microport, Pie Medical, and Recor Medical, and consultancy or speaker fees from Abbott Vascular, Abiomed, ACIST Medical, Boston Scientific, Cardialysis BV, CardiacBooster, Kaminari Medical, Recor Medical, PulseCath, Pie Medical, Sanofi, Siemens Health Care, and Medtronic. Dr Lurz has received institutional grant support from Recor Medical, Edwards Lifesciences, and Abbott. Dr Mahfoud is supported by Deutsche Gesellschaft für Kardiologie (DGK), Deutsche Forschungsgemeinschaft (SFB TRR219, project ID 322900939), and Deutsche Herzstiftung; and has received scientific support from Ablative Solutions, Medtronic, and Recor Medical, and speaker honoraria or consulting fees from Ablative Solutions, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Inari, Medtronic, Merck, Recor Medical, Servier, and Terumo. Dr Schmieder has received grant support and personal fees from Recor Medical, Medtronic, and Ablative Solutions. Dr Basile has received grant support from Recor Medical and Ablative Solutions. Dr Bloch has received personal fees from Recor Medical and Medtronic. Dr Weber has received personal fees from Recor Medical, Medtronic, and Ablative Solutions. Dr Saxena has received grant support from Recor Medical, Ablative Solutions, Applied Therapeutics, Vascular Dynamics, and MSD; and has received consulting fees from Recor Medical, Esperion Inc., Daiichi Sankyo Inc., Novartis, and Vifor Pharma. Dr Wang reports no relationships relevant to the contents of this article to disclose. Dr Sanghvi has received grant support and personal fees from Recor Medical and Medtronic and has received grant support from CSI. Dr Jenkins reports institutional funding to Ochsner Medical Center from Medtronic, Abbott, Abiomed, and Recor Medical; and in addition to research grants, he has received honoraria for speaking engagements or proctoring consulting from Abbott, Recor Medical, and Medtronic. Dr Devireddy has received personal fees from Recor Medical, Medtronic, Edwards Lifesciences, and Shockwave Medical. Dr Rader has received personal fees from Recor Medical, Medtronic, and Bristol Myers Squibb. Dr Gosse has received research grant support from Recor Medical. L. Claude and Dr Dimitri Augustin are employees of Recor Medical. Dr McClure is an employee of NAMSA, a contractor for Recor Medical. Dr Kirtane reports institutional funding to Columbia University or Cardiovascular Research Foundation from Medtronic, Boston Scientific, Abbott Vascular, Abiomed, CSI, CathWorks, Siemens, Philips, and Recor Medical; in addition to research grants, institutional funding includes fees paid to Columbia University or Cardiovascular Research Foundation for speaking engagements or consulting; personal fees for consulting from Neurotronic; and travel expenses or meals from Medtronic, Boston Scientific, Abbott Vascular, Abiomed, CSI, CathWorks, Siemens, Philips, Recor Medical, Chiesi, OpSens, Zoll, and Regeneron.

Endovascular ultrasound renal denervation (uRDN) reduced blood pressure (BP) compared to sham at 2 months in patients with resistant hypertension in the multicenter, blinded, randomized, sham-controlled RADIANCE-HTN TRIO trial. This analysis evaluates longer-term outcomes of patients randomized to uRDN. Patients with resistant hypertension to a 3-drug combination pill were randomized to uRDN (n = 69) or sham (n = 67). From 2-5 months, patients followed a standardized anti-hypertensive medication (AHM) titration protocol. At 6 months, patients were unblinded and received AHM per standard of care. In the uRDN group, 71% (49/69) completed 36-month follow-up. Screening office BP was 159/103 on 3.9 AHM. Baseline office BP on the single-pill combination was 153/99 mmHg. At 36 months, office BP changed by -14.5 ± 26.1/-9.0 ± 14.8 mmHg from screening (p < 0.001 for both) and -8.0 ± 24.5/-5.0 ± 14.6 mmHg from baseline (p = 0.007; p = 0.022) on 3.7 AHM. The efficacy of uRDN was durable to 36 months in patients with resistant hypertension with no safety concerns., Competing Interests: Compliance with ethical standards. Conflict of interest: MJB has received personal fees from Recor Medical and Medtronic. AJK reports institutional funding to Columbia University and/or Cardiovascular Research Foundation from Medtronic, Boston Scientific, Abbott Vascular, Amgen, CSI, Philips, Recor Medical, Neurotronic, Biotronik, Chiesi, Bolt Medical, Magenta Medical, Canon, SoniVie, and Merck. In addition to research grants, institutional funding includes fees paid to Columbia University and/or Cardiovascular Research Foundation for consulting and/or speaking engagements in which AJK controlled the content. Personal: Consulting from IMDS; Travel Expenses/Meals from Medtronic, Boston Scientific, Abbott Vascular, CSI, Siemens, Philips, Recor Medical, Chiesi, OpSens, Zoll, and Regeneron. MA has received research grants from the European Horizon 2020 programme; has received grant support and non-financial support from Recor Medical, Novartis, and Idorsia; and has received personal fees from Alnylam Pharmaceutical, Novartis, Medtronic, Astra Zeneca. FM is supported by Deutsche Gesellschaft für Kardiologie (DGK), Deutsche Forschungsgemeinschaft (SFB TRR219, Project-ID 322900939), and Deutsche Herzstiftung. He has received scientific support from Ablative Solutions, Medtronic and Recor Medical and speaker honoraria/consulting fees from Ablative Solutions, Amgen, Astra Zeneca, Bayer, Boehringer Ingelheim, Inari, Medtronic, Merck, Recor Medical, Servier, and Terumo. JB has reported receiving grants from Recor Medical and Ablative Solutions. JD has received institutional grant/research support from Abbott Vascular, Boston Scientific, ACIST Medical, Medtronic, Microport, Pie Medical, and Recor Medical, and consultancy and speaker fees from Abbott Vascular, Abiomed, ACIST medical, Boston Scientific, Cardialysis BV, CardiacBooster, Kaminari Medical, Recor Medical, PulseCath, Pie Medical, Sanofi, Siemens Health Care and Medtronic. MS has received grant support from Recor Medical, Ablative Solutions, Applied Therapeutics, Vascular Dynamics, and MSD; and has received consulting fees from Recor Medical, Esperion Inc., Daiichi Sankyo Inc., Novartis, and Vifor Pharma. LT is an employee of NAMSA, a contractor for Recor Medical. MM and LC are employees of Recor Medical. RES has received research grants and personal fees from Recor Medical, Medtronic, and Ablative Solutions., (© 2024. The Author(s).)

Importance: 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., Objective: To study the efficacy and safety of ultrasound renal denervation without the confounding influence of antihypertensive medications in patients with hypertension., Design, Setting, and Participants: 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., Interventions: Ultrasound renal denervation vs a sham procedure., Main Outcomes and Measures: 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., Results: 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., Conclusions and Relevance: 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., Trial Registration: ClinicalTrials.gov Identifier: NCT03614260.

Background: Resistant hypertension is associated with increased cardiovascular risk. The endothelin pathway has been implicated in the pathogenesis of hypertension, but it is currently not targeted therapeutically, thereby leaving this relevant pathophysiological pathway unopposed with currently available drugs. The aim of the study was to assess the blood pressure lowering efficacy of the dual endothelin antagonist aprocitentan in patients with resistant hypertension., Methods: PRECISION was a multicentre, blinded, randomised, parallel-group, phase 3 study, which was done in hospitals or research centres in Europe, North America, Asia, and Australia. Patients were eligible for randomisation if their sitting systolic blood pressure was 140 mm Hg or higher despite taking standardised background therapy consisting of three antihypertensive drugs, including a diuretic. The study consisted of three sequential parts: part 1 was the 4-week double-blind, randomised, and placebo-controlled part, in which patients received aprocitentan 12·5 mg, aprocitentan 25 mg, or placebo in a 1:1:1 ratio; part 2 was a 32-week single (patient)-blind part, in which all patients received aprocitentan 25 mg; and part 3 was a 12-week double-blind, randomised, and placebo-controlled withdrawal part, in which patients were re-randomised to aprocitentan 25 mg or placebo in a 1:1 ratio. The primary and key secondary endpoints were changes in unattended office systolic blood pressure from baseline to week 4 and from withdrawal baseline to week 40, respectively. Secondary endpoints included 24-h ambulatory blood pressure changes. The study is registered on ClinicalTrials.gov, NCT03541174., Findings: The PRECISION study was done from June 18, 2018, to April 25, 2022. 1965 individuals were screened and 730 were randomly assigned. Of these 730 patients, 704 (96%) completed part 1 of the study; of these, 613 (87%) completed part 2 and, of these, 577 (94%) completed part 3 of the study. The least square mean (SE) change in office systolic blood pressure at 4 weeks was -15·3 (SE 0·9) mm Hg for aprocitentan 12·5 mg, -15·2 (0·9) mm Hg for aprocitentan 25 mg, and -11·5 (0·9) mm Hg for placebo, for a difference versus placebo of -3·8 (1·3) mm Hg (97·5% CI -6·8 to -0·8, p=0·0042) and -3·7 (1·3) mm Hg (-6·7 to -0·8; p=0·0046), respectively. The respective difference for 24 h ambulatory systolic blood pressure was -4·2 mm Hg (95% CI -6·2 to -2·1) and -5·9 mm Hg (-7·9 to -3·8). After 4 weeks of withdrawal, office systolic blood pressure significantly increased with placebo versus aprocitentan (5·8 mm Hg, 95% CI 3·7 to 7·9, p<0·0001). The most frequent adverse event was mild-to-moderate oedema or fluid retention, occurring in 9%, 18%, and 2% for patients receiving aprocitentan 12·5 mg, 25 mg, and placebo, during the 4-week double-blind part, respectively. This event led to discontinuation in seven patients treated with aprocitentan. During the trial, a total of 11 treatment-emergent deaths occurred, none of which were regarded by the investigators to be related to study treatment., Interpretation: In patients with resistant hypertension, aprocitentan was well tolerated and superior to placebo in lowering blood pressure at week 4 with a sustained effect at week 40., Funding: Idorsia Pharmaceuticals and Janssen Biotech., Competing Interests: Declaration of interests MPS has received institutional grants or contracts and personal consulting fees from Medtronic, Abbott Laboratories, and ReCor Medical; personal payment or honoraria from Medtronic, Abbott Laboratories, Merck, and Servier Laboratories; personal support for attending meetings, travel, or both from Medtronic and Abbott Laboratories; serves as the President of the High Blood Pressure Research Council of Australia; and is on the International Society of Hypertension scientific committee. MB is an employee of Idorsia Pharmaceuticals. MAW is has received consulting fees or performed research services for Janssen, Bristol Myers Squibb, CinCor, Medtronic, ReCor, and Ablative Solutions. PD and RFD are employees of Idorsia Pharmaceuticals and hold stock or stock options in Idorsia Pharmaceuticals. GLB has received consulting fees from Bayer, KBP BioSciences, Ionis Pharmaceuticals, Alnylam Pharmaceuticals, AstraZeneca, Quantum Genomics, Novo Nordisk, Janssen, Dia Medica Therapeutics, and InREGEN. JMF has received consulting fees from Ardelyx, Janssen, Amgen, FibroGen, Teva Pharmaceuticals, and ReCor Medical; and payment for a lecture at a continuing medical education event from Janssen. MS-S is an employee of Idorsia Pharmaceuticals. LPH is an employee of Janssen and holds stock in Janssen. KN has received personal honoraria from Bausch Health, Berlin-Chemie (Menarini Group), Egis, Gedeon Richter, Krka, Medtronic, Merck, Novo Nordisk, Polpharma, Recordati, and Servier Laboratories; and has participated in an advisory board for Idorsia Pharmaceuticals. J-GW declares no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Endovascular renal denervation reduces blood pressure in patients with mild-to-moderate hypertension, but its efficacy in patients with true resistant hypertension has not been shown. We aimed to assess the efficacy and safety of endovascular ultrasound renal denervation in patients with hypertension resistant to three or more antihypertensive medications., Methods: In a randomised, international, multicentre, single-blind, sham-controlled trial done at 28 tertiary centres in the USA and 25 in Europe, we included patients aged 18-75 years with office blood pressure of at least 140/90 mm Hg despite three or more antihypertensive medications including a diuretic. Eligible patients were switched to a once daily, fixed-dose, single-pill combination of a calcium channel blocker, an angiotensin receptor blocker, and a thiazide diuretic. After 4 weeks of standardised therapy, patients with daytime ambulatory blood pressure of at least 135/85 mm Hg were randomly assigned (1:1) by computer (stratified by centres) to ultrasound renal denervation or a sham procedure. Patients and outcome assessors were masked to randomisation. Addition of antihypertensive medications was allowed if specified blood pressure thresholds were exceeded. The primary endpoint was the change in daytime ambulatory systolic blood pressure at 2 months in the intention-to-treat population. Safety was also assessed in the intention-to-treat population. This study is registered with ClinicalTrials.gov, NCT02649426., Findings: Between March 11, 2016, and March 13, 2020, 989 participants were enrolled and 136 were randomly assigned to renal denervation (n=69) or a sham procedure (n=67). Full adherence to the combination medications at 2 months among patients with urine samples was similar in both groups (42 [82%] of 51 in the renal denervation group vs 47 [82%] of 57 in the sham procedure group; p=0·99). Renal denervation reduced daytime ambulatory systolic blood pressure more than the sham procedure (-8·0 mm Hg [IQR -16·4 to 0·0] vs -3·0 mm Hg [-10·3 to 1·8]; median between-group difference -4·5 mm Hg [95% CI -8·5 to -0·3]; adjusted p=0·022); the median between-group difference was -5·8 mm Hg (95% CI -9·7 to -1·6; adjusted p=0·0051) among patients with complete ambulatory blood pressure data. There were no differences in safety outcomes between the two groups., Interpretation: Compared 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., Funding: ReCor Medical., Competing Interests: Declaration of interests MA has received research grants from the French Ministry of Health, Quantum Genomics, and the European Horizon 2020 programme; has received grant support and non-financial support from ReCor Medical and Idorsia; and has received personal fees from CVRx, AstraZeneca, Alnylam Pharmaceutical, and Poxel Pharma. KS has received grant support and personal fees from ReCor Medical and Medtronic, and has received grant support from Cardiovascular Systems. MSax has received grant support and personal fees from ReCor Medical. PG has received grant support from the University Hospital of Bordeaux. LCR has received personal fees from ReCor Medical. APe has received personal fees from Quantum Genomics and grant support from Ablative Solutions, Quantum Genomics, and ReCor Medical. JB has received grant support from ReCor Medical and Ablative Solutions. MJB has received personal fees from ReCor Medical and Medtronic. JD has received grant support from ReCor Medical, Medtronic, Boston Scientific, Abbott Vascular, Acist Medical, AstraZeneca, Pie Medical, and Pulse Cath, and personal fees from ReCor Medical, Medtronic, Acist Medical, Boston Scientific, Pie Medical, and Pulse Cath. MDL has received personal fees from ReCor Medical, Medtronic, CVRx, Ablative Solutions, Vascular Dynamics, ROX Medical, and Tarilan Laser Technologies, and grants from Medtronic. FM is supported by Deutsche Gesellschaft für Kardiologie and Deutsche Forschungsgemeinschaft (SFB TRR 219); and has received grant support and personal fees from ReCor Medical, Medtronic, Berlin Chemie, Bayer, and Boehringer Ingelheim. RES has received grant support and personal fees from ReCor Medical, Medtronic, and Ablative Solutions. ASPS has received personal fees from ReCor Medical, Medtronic, Boston Scientific, and Philips. MAW has received personal fees from ReCor Medical, Medtronic, Boston Scientific, and Ablative Solutions. APa has received grant support and personal fees from ReCor Medical, Medtronic, and Ablative Solutions. DH reports institutional funding to Stamford Hospital from ReCor Medical. SB has received grant support from Abbott Vascular, the National Heart, Lung, and Blood Institute, and REATA; and personal fees from Abbott Vascular, Biotronik, REATA, Amgen, Pfizer, Boehringer Ingelheim, and Meril. JW has received personal fees from ReCor Medical and Medtronic. NCB is an employee of ReCor Medical and is the author on multiple patents in the field of renal denervation. HR-S is an employee of ReCor Medical. LC is an employee of ReCor Medical. CKM is an employee of North American Science Associates and a contractor for ReCor Medical. AJK reports institutional funding (in addition to research grants, institutional funding includes fees paid for speaking engagements or consulting) to Columbia University or the Cardiovascular Research Foundation (New York, NY, USA) from Medtronic, Boston Scientific, Abbott Vascular, Abiomed, Cardiovascular Systems, CathWorks, Siemens, Philips, and ReCor Medical. AJK also reports travel expenses or meals from Medtronic, Boston Scientific, Abbott Vascular, Abiomed, Cardiovascular Systems, CathWorks, Siemens, Philips, Chiesi, OpSens, Zoll, Regeneron, and ReCor Medical. All other authors declare no competing interests., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objectives: Plasma N-terminal pro brain natriuretic peptide (NT-proBNP) and R wave in aVL lead (RaVL) have been associated with mortality in hypertension. The aim of the current study was to compare the prognostic value of their combination to that of the left ventricular mass index (LVMI) assessed by echocardiography., Methods: A total of 1104 hypertensive patients who had at baseline an assessment of plasma NT-proBNP, a 12-lead ECG, and echocardiography were included. LVMI was assessable in 921 patients. After a median (interquartile range) follow-up of 8.5 (5.4-13.3) years, 110 deaths occurred, 62 of which were from a cardiovascular cause., Results: Optimal thresholds of RaVL and plasma NT-proBNP to predict mortality were 0.7 mV and 150 pg/ml, respectively. A three-modality variable based on RaVL and NT-proBNP was built: 0 when none were above the threshold, 1 or 2 when only one or both were above the threshold. After adjustment for all confounders including LVMI indexed to height raised to the allometric power of 2.7 in Cox regression analysis, we observed a significant increased risk for patients having one marker above the threshold for all-cause and cardiovascular mortality [hazard ratio: 1.76; 95% confidence interval (1.08-2.86); 2.18 (1.06-4.46)] and for those having two markers above the threshold [2.76 (1.51-5.03); 3.90 (1.69-9.00)]. The prognostic value of the combination had the highest C-index (0.772 and 0.839, respectively) in comparison with LVMI (0.746 and 0.806, respectively)., Conclusion: Risk stratification in hypertension using the combination of NT-proBNP and RaVL is a simple method that may be considered in first line screening.

Background: 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., Methods: 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., Findings: 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., Interpretation: 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., Funding: ReCor Medical., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: The DENERHTN (Renal Denervation for Hypertension) trial confirmed the efficacy of renal denervation (RDN) in lowering daytime ambulatory systolic blood pressure when added to standardized stepped-care antihypertensive treatment (SSAHT) for resistant hypertension at 6 months., Methods and Results: This post hoc exploratory analysis assessed the impact of abdominal aortic calcifications (AAC) on the hemodynamic and renal response to RDN at 6 months. In total, 106 patients with resistant hypertension were randomly assigned to RDN plus SSAHT or to the same SSAHT alone (control group). Total AAC volume was measured, with semiautomatic software and blind to randomization, from the aortic hiatus to the iliac bifurcation using the prerandomization noncontrast abdominal computed tomography scans of 90 patients. Measurements were expressed as tertiles. The baseline-adjusted difference in the change in daytime ambulatory systolic blood pressure from baseline to 6 months between the RDN and control groups was -10.1 mm Hg ( P =0.0462) in the lowest tertile and -2.5 mm Hg ( P =0.4987) in the 2 highest tertiles of AAC volume. Estimated glomerular filtration rate remained stable at 6 months for the patients in the lowest tertile of AAC volume who underwent RDN (+2.5 mL/min per 1.73 m 2 ) but decreased in the control group (-8.0 mL/min per 1.73 m 2 , P =0.0148). In the 2 highest tertiles of AAC volume, estimated glomerular filtration rate decreased similarly in the RDN and control groups ( P =0.2640)., Conclusions: RDN plus SSAHT resulted in a larger decrease in daytime ambulatory systolic blood pressure than SSAHT alone in patients with a lower AAC burden than in those with a higher AAC burden. This larger decrease in daytime ambulatory systolic blood pressure was not associated with a decrease in estimated glomerular filtration rate., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01570777., (© 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

Introduction: Combination therapy is needed to control blood pressure (BP) in a large number of hypertensive patients with diabetes mellitus. Adherence to treatment is a major clinical problem; therefore, the time duration of the antihypertensive action of a drug determines BP control when a dose is skipped., Objectives: The aim was to determine whether the fixed-dose combination of olmesartan/amlodipine provides equal efficacy and safety as the perindopril/amlodipine combination when a drug dose is missed., Methods: In this noninferiority trial with a randomized, double-blind, double-dummy parallel group, controlled design, 260 patients received either olmesartan 20-40 mg/amlodipine 5-10 mg or perindopril 4-8 mg/amlodipine 5-10 mg for 24 weeks. The main outcome was the sitting office DBP after 24 weeks of treatment at 48 h from last administration., Results: The olmesartan/amlodipine combination reached noninferiority criteria in reduction of office DBP after 24 weeks of treatment and after the missed dose, compared with the perindopril/amlodipine combination (-11.7 and -10.5 mmHg, respectively). Office SBP and pulse pressure were significantly lower in both groups after 24 weeks of treatment and 48 h after the missed dose, observing a trend to greater SBP reduction in the olmesartan/amlodipine group., Conclusions: The combination olmesartan/amlodipine is safe, well tolerated, and as effective as the combination of perindopril/amlodipine in the control of essential hypertension in patients with diabetes mellitus. A missed dose does not leave the patients unprotected in both treatments; however, a faster control with less dose increment is observed with olmesartan/amlodipine.

Background: Conflicting blood pressure-lowering effects of catheter-based renal artery denervation have been reported in patients with resistant hypertension. We compared the ambulatory blood pressure-lowering efficacy and safety of radiofrequency-based renal denervation added to a standardised stepped-care antihypertensive treatment (SSAHT) with the same SSAHT alone in patients with resistant hypertension., Methods: The Renal Denervation for Hypertension (DENERHTN) trial was a prospective, open-label randomised controlled trial with blinded endpoint evaluation in patients with resistant hypertension, done in 15 French tertiary care centres specialised in hypertension management. Eligible patients aged 18-75 years received indapamide 1·5 mg, ramipril 10 mg (or irbesartan 300 mg), and amlodipine 10 mg daily for 4 weeks to confirm treatment resistance by ambulatory blood pressure monitoring before randomisation. Patients were then randomly assigned (1:1) to receive either renal denervation plus an SSAHT regimen (renal denervation group) or the same SSAHT alone (control group). The randomisation sequence was generated by computer, and stratified by centres. For SSAHT, after randomisation, spironolactone 25 mg per day, bisoprolol 10 mg per day, prazosin 5 mg per day, and rilmenidine 1 mg per day were sequentially added from months two to five in both groups if home blood pressure was more than or equal to 135/85 mm Hg. The primary endpoint was the mean change in daytime systolic blood pressure from baseline to 6 months as assessed by ambulatory blood pressure monitoring. The primary endpoint was analysed blindly. The safety outcomes were the incidence of acute adverse events of the renal denervation procedure and the change in estimated glomerular filtration rate from baseline to 6 months. This trial is registered with ClinicalTrials.gov, number NCT01570777., Findings: Between May 22, 2012, and Oct 14, 2013, 1416 patients were screened for eligibility, 106 of those were randomly assigned to treatment (53 patients in each group, intention-to-treat population) and 101 analysed because of patients with missing endpoints (48 in the renal denervation group, 53 in the control group, modified intention-to-treat population). The mean change in daytime ambulatory systolic blood pressure at 6 months was -15·8 mm Hg (95% CI -19·7 to -11·9) in the renal denervation group and -9·9 mm Hg (-13·6 to -6·2) in the group receiving SSAHT alone, a baseline-adjusted difference of -5·9 mm Hg (-11·3 to -0·5; p=0·0329). The number of antihypertensive drugs and drug-adherence at 6 months were similar between the two groups. Three minor renal denervation-related adverse events were noted (lumbar pain in two patients and mild groin haematoma in one patient). A mild and similar decrease in estimated glomerular filtration rate from baseline to 6 months was observed in both groups., Interpretation: In patients with well defined resistant hypertension, renal denervation plus an SSAHT decreases ambulatory blood pressure more than the same SSAHT alone at 6 months. This additional blood pressure lowering effect may contribute to a reduction in cardiovascular morbidity if maintained in the long term after renal denervation., Funding: French Ministry of Health., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Objective: We investigated data in 373 patients from the EXPLOR trial to determine the influence of heart rate (HR) and blood pressure (BP) on aortic stiffness in response to beta-blockade or angiotensin 2 type 1 receptor antagonism, administered during 24 weeks., Methods: Carotid-femoral pulse wave velocity (PWV) was measured with aplanation tonometry (Sphygmocor ) after 8 (W8) and 24 weeks (W24) of treatment by the single-pill combination valsartan-amlodipine (80/5  mg, then 160/10  mg) or an atenolol-amlodipine combination (50/5  mg, then 100/10  mg) in a prospective, randomized, parallel-groups multicenter trial with PROBE design. Drugs were up-titrated at W8. We analyzed the changes in PWV in relation with the changes in BP and HR, and major covariates, using mixed models in each treatment arm., Results: The unadjusted reductions in mean BP and PWV were not significantly different between groups. HR was significantly reduced in the atenolol group, but not in the valsartan group. After adjustment on BP and HR, PWV significantly decreased with valsartan [-0.37  m/s (-0.70 to -0.08) at W8 and -0.43 (-0.76 to -0.10) m/s at W24], whereas no significant change was observed after atenolol [-0.16  m/s (-0.49 to 0.17) at W8 and -0.05 (-0.35 to 0.44) m/s at W24]., Conclusion: These findings suggest that the reduction in PWV observed after atenolol could be explained by changes in BP and HR, whereas in patients treated by valsartan, about half of the decrease in aortic stiffness was BP-independent.

The beta-blocker atenolol is less effective than angiotensin-receptor blockers and calcium-channel blockers for reducing central blood pressure (BP). The trial was designed to determine whether the advantages of angiotensin-receptor blockers over atenolol remained significant when both were combined with the calcium-channel blocker amlodipine. A prospective, randomized, blinded endpoint (PROBE design) parallel group, multicenter trial including 393 patients with essential hypertension resistant to 4 weeks of 5 mg of amlodipine was set out. Central systolic BP, augmentation index (AIx; either rough or adjusted on heart rate), and carotid-to-femoral pulse wave velocity were measured with applanation tonometry (SphygmoCor) at inclusion and after 8 and 24 weeks of active treatment with an amlodipine-valsartan combination (5/80 mg and then 10/160 mg) or an amlodipine-atenolol combination (5/50 mg and then 10/100 mg). From baseline to week 24, central systolic BP decreased significantly more in the amlodipine-valsartan group (-13.70+/-1.15 mm Hg; P<0.0001) than in the amlodipine-atenolol group (-9.70+/-1.10 mm Hg; P<0.0001; difference: -4.00 mm Hg [95% CI: -7.10 to -0.90]; P=0.013), despite similar changes in brachial systolic BP. The difference in rough AIx reduction was -6.5% (95% CI: -8.3 to -4.7; P<0.0001) in favor of amlodipine-valsartan. AIx adjusted on heart rate was significantly reduced in favor of amlodipine-valsartan (-2.8% [95% CI: -4.92 to -0.68]; P<0.01). Heart rate decreased significantly more with amlodipine-atenolol (difference: -11 bpm [95% CI: -14 to -8 bpm]; P<0.001). Pulse wave velocity decreased by 0.95 m/s in both groups with no significant difference. Differences in central systolic BP and rough AIx remained significant after adjustment to the changes in heart rate. The amlodipine-valsartan combination decreased central (systolic and pulse) pressure and AIx more than the amlodipine-atenolol combination.