Showing papers by "Roland E. Schmieder published in 2019"

Effects of renal denervation on kidney function and long-term outcomes: 3-year follow-up from the Global SYMPLICITY Registry.

Abstract: AIMS Several studies and registries have demonstrated sustained reductions in blood pressure (BP) after renal denervation (RDN). The long-term safety and efficacy after RDN in real-world patients with uncontrolled hypertension, however, remains unknown. The objective of this study was to assess the long-term safety and efficacy of RDN, including its effects on renal function. METHODS AND RESULTS The Global SYMPLICITY Registry is a prospective, open-label registry conducted at 196 active sites worldwide in hypertensive patients receiving RDN treatment. Among 2237 patients enrolled and treated with the SYMPLICITY Flex catheter, 1742 were eligible for follow-up at 3 years. Baseline office and 24-h ambulatory systolic BP (SBP) were 166 ± 25 and 154 ± 18 mmHg, respectively. SBP reduction after RDN was sustained over 3 years, including decreases in both office (-16.5 ± 28.6 mmHg, P < 0.001) and 24-h ambulatory SBP (-8.0 ± 20.0 mmHg; P < 0.001). Twenty-one percent of patients had a baseline estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2. Between baseline and 3 years, renal function declined by 7.1 mL/min/1.73 m2 in patients without chronic kidney disease (CKD; eGFR ≥60 mL/min/1.73 m2; baseline eGFR 87 ± 17 mL/min/1.73 m2) and by 3.7 mL/min/1.73 m2 in patients with CKD (eGFR <60 mL/min/1.73 m2; baseline eGFR 47 ± 11 mL/min/1.73 m2). No long-term safety concerns were observed following the RDN procedure. CONCLUSION Long-term data from the Global SYMPLICITY Registry representing the largest available cohort of hypertensive patients receiving RDN in a real-world clinical setting demonstrate both the safety and efficacy of the procedure with significant and sustained office and ambulatory BP reductions out to 3 years.

Six-Month Results of Treatment-Blinded Medication Titration for Hypertension Control After Randomization to Endovascular Ultrasound Renal Denervation or a Sham Procedure in the RADIANCE-HTN SOLO Trial

Abstract: Background: The multicenter, international, randomized, blinded, sham-controlled RADIANCE-HTN SOLO trial (A Study of the ReCor Medical Paradise System in Clinical Hypertension) demonstrated a 6.3 m...

How does empagliflozin improve arterial stiffness in patients with type 2 diabetes mellitus? Sub analysis of a clinical trial

Abstract: Empagliflozin has been shown to reduce cardiovascular mortality, but the underlying pathogenetic mechanisms are poorly understood. It was previously demonstrated that empagliflozin improved arterial stiffness. Our analysis comprising 58 patients with type 2 diabetes mellitus identifies factors triggering the improvement of arterial stiffness. All patients participated in an investigator-initiated, prospective, double-blind, randomized, placebo-controlled, interventional clinical trial ( http://www.ClinicalTrials.gov : NCT02471963, registered 15th June 2015, retrospectively registered) and received either 6-weeks treatment with 25 mg empagliflozin orally once daily or placebo (crossover). Central systolic pressure and central pulse pressure were recorded by the SphygmoCor System (AtCor Medical). Now, we investigated the impact of parameters of glucose metabolism, volume status, sympathetic activation, lipids, uric acid, blood pressure and inflammation on vascular parameters of arterial stiffness using multivariate regression analysis. As previously reported, therapy with empagliflozin improved arterial stiffness as indicated by reduced central systolic blood pressure (113.6 ± 12.1 vs 118.6 ± 12.9 mmHg, p < 0.001), central pulse pressure (39.1 ± 10.2 vs 41.9 ± 10.7 mmHg, p = 0.027) forward (27.1 ± 5.69 vs 28.7 ± 6.23 mmHg, p = 0.031) as well as reflected wave amplitude (18.9 ± 5.98 vs 20.3 ± 5.97 mmHg, p = 0.045) compared to placebo. The multivariate regression analysis included age, sex and change between empagliflozin and placebo therapy of the following parameters: HbA1c, copeptin, hematocrit, heart rate, LDL-cholesterol, uric acid, systolic 24-h ambulatory blood pressure and high sensitive CRP (hsCRP). Besides the influence of age (beta = − 0.259, p = 0.054), sex (beta = 0.292, p = 0.040) and change in systolic 24-h ambulatory blood pressure (beta = 0.364, p = 0.019), the change of hsCRP (beta = 0.305, p = 0.033) emerged as a significant determinant of the empagliflozin induced reduction in arterial stiffness (placebo corrected). When replacing HbA1c with fasting plasma glucose in the multivariate regression analysis, a similar effect of the change in hsCRP (beta = 0.347, p = 0.017) on arterial stiffness parameters was found. Besides age and sex, change in systolic 24-h ambulatory blood pressure and change in hsCRP were determinants of the empagliflozin induced improvement of vascular parameters of arterial stiffness, whereas parameters of change in glucose metabolism and volume status had no significant influence. Our analysis suggests that empagliflozin exerts, at least to some extent, its beneficial vascular effects via anti-inflammatory mechanisms. Trial registration http://www.ClinicalTrials.gov : NCT02471963, registered 15th June 2015, retrospectively registered

Renal Denervation for Treating Hypertension: Current Scientific and Clinical Evidence

Abstract: Initial studies of catheter-based renal denervation (RDN) for uncontrolled HTN using radiofrequency ablation in the main renal arteries showed that RDN was effective in lowering office blood pressure (BP). However, the first randomized sham-controlled trial, SYMPLICITY-HTN-3, did not show significantly lower office or 24-h ambulatory systolic BP compared with sham treatment. Subsequent studies in both animals and humans demonstrated the potential importance of more distal and branch renal artery radiofrequency ablation, and a second-generation multielectrode system became available. Two recent randomized sham-controlled trials in patients not taking antihypertensive drugs (SPYRAL HTN-OFF MED) or continuing to take drugs (SPYRAL HTN-ON MED) performed RDN with the second-generation radiofrequency ablation system using an ablation protocol that included treatment of the distal renal artery as well as the branch renal arteries. These studies showed that RDN significantly reduced office and 24-h ambulatory BP compared with sham treatment. Another recent randomized sham-controlled trial in patients not receiving medications showed that RDN with catheter-based ultrasound (RADIANCE-HTN SOLO) applied in just the main renal arteries significantly lowered daytime ambulatory and office BP compared with sham treatment. These trials have renewed clinical and scientific interest in defining the appropriate role of RDN in hypertension treatment. In addition, other important issues will need to be addressed in the future such as the development of tests to determine the extent of RDN at the time of the procedure and the potential of renal nerve fibers to regain their patency at some later stage following the ablation procedure.

Cardiovascular outcomes and achieved blood pressure in patients with and without diabetes at high cardiovascular risk

Abstract: AIMS Studies have shown a non-linear relationship between systolic blood pressure (SBP) and diastolic blood pressure (DBP) and outcomes, with increased risk observed at both low and high blood pressure (BP) levels. We hypothesized that the BP-risk association is different in individuals with and without diabetes at high cardiovascular risk. METHODS AND RESULTS We identified patients with (N = 11 487) or without diabetes (N = 19 450), from 30 937 patients, from 133 centres in 44 countries with a median follow-up of 56 months in the ONTARGET/TRANSCEND studies. Patients had a prior history of stroke, myocardial infarction (MI), peripheral artery disease, or were high-risk diabetics. Patients in ONTARGET had been randomized to ramipril 10 mg daily, telmisartan 80 mg daily, or the combination of both. Patients in TRANSCEND were ACE intolerant and randomized to telmisartan 80 mg daily or matching placebo. We analysed the association of mean achieved in-trial SBP and DBP with the composite outcome of cardiovascular death, MI, stroke and hospitalization for congestive heart failure (CHF), the components of the composite, and all-cause death. Data were analysed by Cox regression and restricted cubic splines, adjusting for risk markers including treatment allocation and accompanying cardiovascular treatments. In patients with diabetes, event rates were higher across the whole spectrum of SBP and DBP compared with those without diabetes (P < 0.0001 for the primary composite outcome, P < 0.01 for all other endpoints). Mean achieved in-trial SBP ≥160 mmHg was associated with increased risk for the primary outcome [diabetes/no diabetes: adjusted hazard ratio (HR) 2.31 (1.93-2.76)/1.66 (1.36-2.02) compared with non-diabetics with SBP 120 to <140 mmHg], with similar findings for all other endpoints in patients with diabetes, and for MI and stroke in patients without diabetes. In-trial SBP <120 mmHg was associated with increased risk for the combined outcome in patients with diabetes [HR 1.53 (1.27-1.85)], and for cardiovascular death and all-cause death in all patients. In-trial DBP ≥90 mmHg was associated with increased risk for the primary outcome [diabetes/no diabetes: HR 2.32 (1.91-2.82)/1.61 (1.35-1.93) compared with non-diabetics with DBP 70 to <80 mmHg], with similar findings for all other endpoints, but not for CHF hospitalizations in patients without diabetes. In-trial DBP <70 mmHg was associated with increased risk for the combined outcome in all patients [diabetes/no diabetes: HR 1.77 (1.51-2.06)/1.30 (1.16-1.46)], and also for all other endpoints except stroke. CONCLUSION High on treatment BP levels (≥160 or ≥90 mmHg) are associated with increased risk of cardiovascular outcomes and death. Also low levels (<120 or <70 mmHg) are associated with increased cardiovascular outcomes (except stroke) and death. Patients with diabetes have consistently higher risks over the whole BP range, indicating that achieving optimal BP goals is most impactful in this group. These data favour guidelines taking lower BP boundaries into consideration, in particular in diabetes. CLINICAL TRIAL REGISTRATION http://clinicaltrials.gov.Unique identifier: NCT00153101.

Guía ESC/ESH 2018 sobre el diagnóstico y tratamiento de la hipertensión arterial

Abstract: Autores/Miembros del Grupo de Trabajo: Bryan Williams* (coordinador de la ESC) (Reino Unido), Giuseppe Mancia* (coordinador de la ESH) (Italia), Wilko Spiering (Países Bajos), Enrico Agabiti Rosei (Italia), Michel Azizi (Francia), Michel Burnier (Suiza), Denis L. Clement (Bélgica), Antonio Coca (España), Giovanni de Simone (Italia), Anna Dominiczak (Reino Unido), Thomas Kahan (Suecia), Felix Mahfoud (Alemania), Josep Redon (España), Luis Ruilope (España), Alberto Zanchetti† (Italia), Mary Kerins (Irlanda), Sverre E. Kjeldsen (Noruega), Reinhold Kreutz (Alemania), Stephane Laurent (Francia), Gregory Y.H. Lip (Reino Unido), Richard McManus (Reino Unido), Krzysztof Narkiewicz (Polonia), Frank Ruschitzka (Suiza), Roland E. Schmieder (Alemania), Evgeny Shlyakhto (Rusia), Costas Tsioufis (Grecia), Victor Aboyans (Francia) e Ileana Desormais (Francia)

Patient preference for therapies in hypertension: a cross-sectional survey of German patients

Abstract: Hypertension is poorly controlled in numerous patients despite effective medication being available. Catheter-based renal denervation (RDN) has emerged as an alternative treatment option. We aimed to assess how likely patients with elevated blood pressure (BP) are to accept RDN as treatment option. A questionnaire-based cross-sectional survey was performed in patients with elevated BP in Germany. Data on patient demographics, clinical characteristics and treatment preferences were collected, anonymized and analyzed. One thousand and eleven patients completed the survey. Mean age was 66 years (55% male). If not already on medication (n = 172), 38.2% of patients would prefer RDN. Of those already on drug therapy (n = 839), 28.2% would opt for RDN. Patients who were pro-RDN were younger (p < 0.0001) and more often male (p < 0.0001). Nineteen percent would choose RDN if it lowered systolic BP by at least 20 mmHg, more than 40% if they did not have to take any more pills thereafter, and 30% if it would lower BP by at least 10 mmHg. Experiences of side effects and drug adherence were identified as determinants of patient preference. Physicians were the main source of information regarding medical problems (95.5%) and influence patients’ decision regarding therapies (98%). This survey found that a significant proportion of patients would choose catheter-based RDN over lifelong pharmacotherapy. These patients were younger and more likely to be male but their expectation of the extent of BP decrease with RDN was high. Physicians are key mediators for treatment selection. They need to incorporate patient preferences into shared decision making.

Tissue sodium content in patients with type 2 diabetes mellitus

Abstract: Background Tissue sodium content by 23Na magnetic resonance imaging (MRI) has been found to be increased in arterial hypertension. We analyzed whether tissue sodium content is increased in patients with type-2 diabetes (T2DM). Methods Patients with T2DM were compared to those with primary hypertension. Patients with T2DM were off any antidiabetic and hypertensive patients off any antihypertensive therapy for at least 4 weeks. Skin and muscle sodium content was assessed non-invasively with a 3.0 T clinical MRI system (Magnetom Verio, Siemens Health Care, Erlangen, Germany) in each patient. Results In patients with T2DM (N = 59) we observed significantly greater muscle sodium content (diabetes: 20.6 ± 3.5 vs hypertension: 16.3 ± 2.5 mmol/l, p Conclusion Patients with T2DM have greater skin and muscle sodium content. These are the first known data to demonstrate increased tissue sodium content in patients with T2DM, measured by 23Na magnetic resonance imaging. Since tissue sodium content is related to organ damage, therapeutic intervention should aim at reducing tissue sodium content.

Changes in 24-Hour Patterns of Blood Pressure in Hypertension Following Renal Denervation Therapy.

Abstract: The hypertension paradox was described over 10 years ago to stress the growing incidence of hypertension despite the availability of safe, effective, and inexpensive drug therapies. Multiple factors contribute to the hypertension paradox, including lack of patient awareness and education, failure to adhere to prescribed lifestyle changes and prescribed drug regimens, aging societal demographics, and recent recommendations for lowered blood pressure goals. Hence, a rationale exists for procedural-based therapy options that could augment drug therapy regimens and help more patients achieve and sustain blood pressure goals. Percutaneous renal denervation has gained continued scientific and clinical interest due to its proven impact on autonomic function, likely because of both efferent and afferent mechanisms affecting the renal nerves. Clinical evidence suggests a strong association between renal denervation and reduced indices of sympathetic tone including muscle sympathetic nerve activity and renal norepinephrine spillover. Historically, surgical sympathetic denervation was shown to improve mortality, independent of its effect on blood pressure. In 2014, the randomized sham-controlled SYMPLICTY HTN-3 trial reported blood pressure drops in the renal denervation-treated group which were nearly matched by those in the sham control group. More recently however, 3 new multicenter, international, prospective, randomized, shamcontrolled clinical trials have demonstrated lower blood pressure after catheter-based renal denervation in uncontrolled hypertensive patients in both the presence and absence of concomitant drug therapy, confirming the biological proof of principle. These trials have rekindled scientific and clinical interest in the procedure and have also revealed interesting new insights into the 24-hour profile of blood pressure reduction associated with the therapy. This review highlights the 24-hour circadian pattern of blood pressure lowering after renal denervation and hypothesize how these effects might complement drug therapy. 24-Hour Blood Pressure Monitoring: Toward Perfect Control The advent of 24-hour ambulatory monitoring has allowed consideration of blood pressure as a continuous and dynamic circadian physiological signal, especially highlighting the unique blood pressure characteristics of the nighttime and early morning period. Thus, blood pressure control has been more meaningfully redefined relative to specific times of day (Figure 1). Circadian blood pressure variability is a direct reflection of the relative integrity of the autonomic nervous system which modulates its behavior. Multiple clinical trials have demonstrated that elevated nighttime blood pressure is more strongly associated with cardiovascular risk than daytime or office blood pressure. Furthermore, 24-hour blood pressure patterns distinguish between different hypertension phenotypes including white coat, masked and sustained hypertension as well as identifying abnormal nighttime dipping patterns. Recently, an analysis of the Spanish Ambulatory Blood Pressure registry with >60 000 patients enrolled, indicated that white-coat hypertension, defined by an out of office 24-hour ambulatory blood pressure lower than goal blood pressure and in-office blood pressure that was above goal in unmedicated patients, was associated with increased mortality, and that masked hypertension was associated with a greater risk of death than sustained hypertension. Indeed, out of office ambulatory (ABPM) or home blood pressure measurement is now recommended to confirm the diagnosis of hypertension and, in the case of home blood pressure measurement, to monitor therapy efficacy in both the United States and European Hypertension Guidelines. Despite these recommendations, ABPM monitoring is used relatively rarely in clinic to confirm the diagnosis of hypertension, even among patients treated by hypertension specialists. Likewise, only recently has ambulatory blood pressure become the focus end point for clinical trials. Ideal blood pressure control includes 24-hour control, adequate circadian rhythm, and appropriate

Effects of renal denervation on blood pressure in hypertensive patients with end-stage renal disease: a single centre experience.

Abstract: Sympathetic nerve activity is a hallmark of hypertension in end-stage renal disease (ESRD). An initial proof-of-concept study implies that renal denervation (RDN) is feasible and safe in RDN, but overall data are limited. In this single-centre prospective pilot study six patients with ESRD and treatment resistant hypertension were consecutively included. Ambulatory blood pressure (ABP) was measured before and 6 months after RDN (Symplictiy Flex™, Medtronic Inc., Santa Rosa, CA). Moreover, haemodialysis parameters which may affect BP reduction were monitored closely. In all patients bilateral RDN was successful done, without documentation of peri- or postprocedural complications. There was a significant reduction in 24-h ABP by 20 ± 17/15 ± 12 mmHg 6 months after RDN (systolic: 163 ± 16 versus 143 ± 9 mmHg, p = 0.043; diastolic: 96 ± 9 versus 81 ± 15 mmHg, p = 0.043), with similar results for day-, and nighttime values, respectively. Antihypertensive medication was kept stable as well as there was no change in haemodialysis parameters during follow-up. In addition, ultrafiltration/week (1.4 ± 1.4 versus 2.2 ± 1.4 l, p = 0.08) as well as hematocrit (measured at baseline and 6 months after RDN) (33.7 ± 4.3 versus 33.1 ± 3.9%, p = 0.715) revealed no change in volume status. Our single-centre pilot study not only supports current data on renal safety of RDN even in small arteries of patients with ESRD, but also enhances the knowledge towards an effective ABP reduction in this type of hypertensive patients.

Effects of the nitric oxide synthase inhibitor ronopterin (VAS203) on renal function in healthy volunteers.

Abstract: Aims Reduced nitric oxide (NO) availability may adversely affect renal perfusion and glomerular filtration. The aim of the present study was to characterize in detail the pharmacological effects of VAS203, an inhibitor of NO synthase, on renal haemodynamics in humans. Methods This double-blind, randomized, placebo-controlled, cross-over phase-I-study comprised 18 healthy men. Renal haemodynamics were assessed with constant-infusion input-clearance technique with p-aminohippurate and inulin for renal plasma flow (RPF) and glomerular filtration rate (GFR), respectively. After baseline measurement, a constant infusion of the tetrahydrobiopterin analogue ronopterin (VAS203, total 10 mg/kg body weight) or placebo was administered at random order for 6 hours additionally. After a wash-out phase of 28 days, the second course was applied. In parallel, markers of early kidney injury and renal function were assessed repeatedly up to 48 hours after starting VAS203/placebo-infusion. Results VAS203-infusion resulted in a significant decrease of RPF (P .20) have been observed. Conclusions Our phase-I-study in healthy humans indicates that VAS203 (10 mg/kg body weight) reduces renal perfusion and glomerular function within the physiological range mainly due to vasoconstriction at the preglomerular site.

Comments on the guidelines (2018) of the European Society of Cardiology (ESC) and the European Society of Hypertension (ESH) on the management of arterial hypertension

Abstract: Die arterielle Hypertonie ist die haufigste chronische Erkrankung, die zu Komplikationen wie Schlaganfall, Demenz, Herzinfarkt und Herzinsuffizienz sowie Niereninsuffizienz fuhren kann. Die Zahl der hypertensiven Patienten wird bis 2025 weltweit auf bis zu 1,6 Mrd. Menschen ansteigen. Die neuen Leitlinien der Europaischen Gesellschaft fur Kardiologie (ESC) und der Europaischen Gesellschaft fur Hypertonie (ESH) zum Management der arteriellen Hypertonie ersetzen die Leitlinien der ESC/ESH aus dem Jahr 2013. Die 2018 Leitlinien der ESC/ESH werden von der Deutschen Gesellschaft fur Kardiologie und der Deutschen Hochdruckliga ubernommen. Im vorliegenden Kommentar werden nationale Besonderheiten herausgearbeitet und die wesentlichen neuen Aspekte der Leitlinie kritisch diskutiert. Hierzu gehoren unter anderem die Definition der arteriellen Hypertonie, die Wichtigkeit von praxisunabhangigen („out-of-office“) Blutdruckmessungen, neue Blutdruckziele, der geanderte Algorithmus zur medikamentosen Therapie sowie die Bedeutung Device-basierter Hochdrucktherapien. Auch werden wichtige Aspekte zur Behandlung von hypertensiven Notfallen vorgestellt.

Evidence of neurodegeneration in individuals with only mildly elevated blood pressure.

Abstract: OBJECTIVE Initiation of antihypertensive drug treatment in low-risk individuals with grade 1 hypertension is under debate. The aim of this study was to examine the impact of mildly elevated blood pressure (BP) on early neurodegenerative processes independent of ageing. METHODS Sixty-two individuals were included in this study: 25 young (aged <40 years) and 37 older (aged ≥40 years) individuals at low cardiovascular risk and grade 1 hypertension at most. Macular retinal layer volumes of both eyes were determined by SD-OCT. Total retinal volume but also each inner retinal layer volume separately including retinal nerve fiber layer (RNFL), ganglion cell layer (GCL), inner plexiform layer (IPL), and GCL-IPL were measured in each individual. RESULTS Retinal layer volumes were lower among older individuals compared with young individuals (RNFL right eye: P = 0.037/left eye: P = 0.021; GCL and GCL-IPL: both eyes P < 0.001; IPL right eye: P = 0.005/left eye: P = 0.002; total retinal volume: both eyes P = 0.002) and there was an inverse correlation between retinal layer volumes and age. Partial correlation analysis, excluding age as a cofactor, revealed an inverse association between retinal layer volumes and DBP. In multiple regression analysis, DBP was identified as a determinant of retinal neurodegenerative processes. CONCLUSION In the current study, we observed an inverse association between retinal neurodegenerative processes and DBP, suggesting that BP-lowering therapy by early antihypertensive drug-treatment might be beneficial to avoid early neurodegeneration.

Kommentar zu den Leitlinien (2018) der Europäischen Gesellschaft für Kardiologie (ESC) und der Europäischen Gesellschaft für Hypertonie (ESH) für das Management der arteriellen Hypertonie

Abstract: Die arterielle Hypertonie ist die haufigste chronische Erkrankung, die zu Komplikationen wie Schlaganfall, Demenz, Herzinfarkt und Herzinsuffizienz sowie Niereninsuffizienz fuhren kann. Die Zahl der hypertensiven Patienten wird bis 2025 weltweit auf bis zu 1,6 Mrd. Menschen ansteigen. Die neuen Leitlinien der Europaischen Gesellschaft fur Kardiologie (ESC) und der Europaischen Gesellschaft fur Hypertonie (ESH) zum Management der arteriellen Hypertonie ersetzen die Leitlinien der ESC/ESH aus dem Jahr 2013. Die 2018 Leitlinien der ESC/ESH werden von der Deutschen Gesellschaft fur Kardiologie und der Deutschen Hochdruckliga ubernommen. Im vorliegenden Kommentar werden nationale Besonderheiten herausgearbeitet und die wesentlichen neuen Aspekte der Leitlinie kritisch diskutiert. Hierzu gehoren unter anderem die Definition der arteriellen Hypertonie, die Wichtigkeit von praxisunabhangigen („out-of-office“) Blutdruckmessungen, neue Blutdruckziele, der geanderte Algorithmus zur medikamentosen Therapie sowie die Bedeutung Device-basierter Hochdrucktherapien. Auch werden wichtige Aspekte zur Behandlung von hypertensiven Notfallen vorgestellt.

New data, new studies, new hopes for renal denervation in patients with uncontrolled hypertension.

Abstract: Background following the publication of SYMPLICITY HTN-3 the field of renal of denervation was put on hold. Although SYMPLICITY HTN-3 was well-designed and sham-controlled trial it failed to show any meaningful reduction in office or 24 h ambulatory blood pressure. The procedure was however safe and allowed research to continue. Although several pitfalls of the study have been pointed out, incomplete renal denervation was also implicated. Since then, a great deal of basic and clinical research took place and will be briefly commented on in this article. Methods and results Before and after SYMPLICITY-HTN-3, numerous uncontrolled, single or unblinded studies have shown substantial office BP reduction ranging from −7.7 to −32 mmHg and ambulatory BP ranging from −2.2 to 10.2 mmHg. Average weighted office systolic BP reduction was −20.8 mmHg and weighted average 24 h ambulatory BPM reduction was −7.8 mmHg. National and international registries have shown similar BP reductions, but results remained unconvincing due to lack of reliable sham controls. In recent years, 5 well-designed sham – controlled studies (beyond, SYMPLICITY-HTN-3) have been published. Of those studies two were single center and three were multicenter international studies. Four studies used single tip or multi-electrode, radiofrequency catheters and one used focused ultrasound. The three multicenter studies reported positive-placebo subtracted results and established BP reductions measured both in the office and by ambulatory monitoring. No serious adverse events were reported. Conclusions It can therefore be concluded that the latest sham controlled studies established efficacy and safety of renal denervation.