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

Background: Renal denervation (RDN) has been shown to lower blood pressure (BP), but its effects on cardiovascular events have only been preliminarily evaluated. Time in therapeutic range (TTR) of BP is associated with cardiovascular events. Objectives: This study sought to assess the impact of catheter-based RDN on TTR and its association with cardiovascular outcomes in the GSR (Global SYMPLICITY Registry). Methods: Patients with uncontrolled hypertension were enrolled and treated with radiofrequency RDN. Office and ambulatory systolic blood pressure (OSBP and ASBP) were measured at 3, 6, 12, 24, and 36 months postprocedure and used to derive TTR. TTR through 6 months was assessed as a predictor of cardiovascular events from 6 to 36 months using a Cox proportional hazard regression model. Results: As of March 1, 2022, 3,077 patients were enrolled: 42.2% were female; mean age was 60.5 ± 12.2 years; baseline OSBP was 165.6 ± 24.8 mm Hg; and baseline ASBP was 154.3 ± 18.7 mm Hg. Patients were prescribed 4.9 ± 1.7 antihypertensive medications at baseline and 4.8 ± 1.9 at 36 months. At 36 months, mean changes were −16.7 ± 28.4 and −9.0 ± 20.2 mm Hg for OSBP and ASBP, respectively. TTR through 6 months was 30.6%. A 10% increase in TTR after RDN through 6 months was associated with significant risk reductions from 6 to 36 months of 15% for major adverse cardiovascular events (P < 0.001), 11% cardiovascular death (P = 0.010), 15% myocardial infarction (P = 0.023), and 23% stroke (P < 0.001). Conclusions: There were sustained BP reductions and higher TTR through 36 months after RDN. A 10% increase in TTR through 6 months was associated with significant risk reductions in major cardiovascular events from 6 to 36 months. (Global SYMPLICITY Registry [GSR] DEFINE; NCT01534299)

Background: Activity of the sympathetic nervous system is increased in patients with hypertension and chronic kidney disease (CKD). Here we compare short-and long-term blood pressure (BP)-lowering effects of renal denervation (RDN) between hypertensive patients with or without CKD in the Global SYMPLICITY Registry. Methods: Office and 24-h ambulatory BP (ABP) were assessed at prespecified time points after RDN. The presence of CKD was defined according to the estimated glomerular filtration rate (eGFR) and enrolled patients were stratified based on the presence (n = 475, eGFR <60 mL/min/1.73 m2) or absence (n = 1505, eGFR ≥60mL/min/1.73 m2) of CKD. Results: Patients with CKD were older (P < 0.001) and were prescribed more antihypertensive medications (P < 0.001). eGFR decline per year was not significantly different between groups after the first year. Office and 24-h ABP were significantly reduced from baseline at all time points after RDN in both groups (all P < 0.001). After adjusting for baseline data, patients without CKD had a greater reduction in office systolic BP (-17.3 ± 28.3 versus-11.7 ± 29.9 mmHg; P = 0.009) but not diastolic BP at 36 months compared with those with CKD. Similar BP and eGFR results were found when the analysis was limited to patients with both baseline and 36-month BP data available. There was no difference in the safety profile of the RDN procedure between groups. Conclusions: After adjusting for baseline data, 24-h systolic and diastolic ABP reduction were similar in patients with and without CKD after RDN, whereas office systolic but not diastolic BP was reduced less in patients with CKD. We conclude that RDN is an effective antihypertensive treatment option in CKD patients.

Background:Diabetes and hypertension are risk factors for renal and cardiovascular outcomes. Data on the association of achieved blood pressure (BP) with renal outcomes in patients with and without diabetes are sparse. We investigated the association of achieved SBP, DBP with renal outcomes and urinary albumin excretion (UAE) in people with vascular disease.Methods:In this pooled analysis, we assessed renal outcome data from high-risk patients aged 55 years or older with a history of cardiovascular disease, 70% of whom had hypertension, randomized to The Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial and to Telmisartan Randomized Assessment Study in ACE Intolerant Subjects with Cardiovascular Disease trials investigating telmisartan, ramipril and their combination with a median follow-up of 56 months. Standardized office BP was measured every 6 months, estimated glomerular filtration rate (eGFR) and UAE at baseline, 2 years and study end. Associations of mean achieved BP on treatment were investigated on major renal outcomes including end-stage renal disease (ESRD), decline of eGFR by at least 40%, doubling of creatinine and the composites thereof and on UAE. Analyses were by Cox regression analysis, analysis of variance and Chi2-Test. Of 30 937 patients with complete data, 19 450 patients without and 11 487 with diabetes were enrolled between 1 December 2001 and 31 July 2003 and followed until 31 July 2008. Data were pooled as the outcomes for telmisartan 80 mg/day (n = 2903) or placebo (n = 2907) for Telmisartan Randomized Assessment Study in ACE Intolerant Subjects with Cardiovascular Disease and ramipril 10 mg/day (n = 8407), telmisartan 80 mg/day (n = 8386) or the combination of both (n = 8334) were similar.Results:For both those with and without diabetes, the hazard ratios for the composites ESRD or doubling of serum creatinine (707 events overall) and ESRD or 40% eGFR loss (2371 events overall) reached a nadir at achieved SBP

Background:Guidelines recommend to start blood pressure (BP)-lowering drugs also according to cardiovascular risk including history of cardiovascular events. We hypothesized that in patients with a history of myocardial infarction (MI), stroke, both or none of those, the index events predict the next event and have different SBP risk associations to different cardiovascular outcomes.Design and measurements:In this pooled posthoc, nonprespecified analysis, we assessed outcome data from high-risk patients aged 55 years or older with a history of cardiovascular events or proven cardiovascular disease, randomized to the Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial and to Telmisartan Randomized Assessment Study in ACE Intolerant Subjects with Cardiovascular Disease Trial investigating telmisartan, ramipril and their combination with a median follow-up of 56 months. Standardized office BP was measured every 6 months. Associations of mean achieved BP on treatment were investigated on MI, stroke and cardiovascular death. We identified patients with previous MI (N = 13 487), stroke (N = 4985), both (N = 1509) or none (N = 10 956) of these index events. Analyses were done by Cox regression, analysis of variance and Chi2-test. 30 937 patients with complete data were enrolled between 1 December 2001 and 31 July 2003, and followed until 31 July 2008. Data of both trials were pooled as the outcomes were similar.Results:Patients with MI as index event had a higher risk to experience a second MI [hazard ratio 1.42 (confidence interval (CI) 1.20-1.69), P < 0.0001] compared with patients with no events but no increased risk for a stroke as a next event [hazard ratio 0.95 (CI 0.73-1.23), n.s.]. The risk was roughly doubled when they had both, MI and stroke before [hazard ratio 2.07 (CI 1.58-2.71), P < 0.0001]. Patients with a stroke history had a roughly three-fold higher likelihood to experience a second stroke [hazard ratio 2.89 (CI 2.37-3.5

This ESH Position Paper 2021 with updated proposed recommendations was deemed necessary after the publication of a set of new pivotal sham-controlled randomized clinical trials (RCTs), which provided important information about the efficacy and safety of endovascular device-based renal denervation (RDN) for hypertension treatment. RDN is effective in reducing or interrupting the sympathetic signals to the kidneys and decreasing whole body sympathetic activity. Five independent, fully completed, sham-controlled RCTs provide conclusive evidence that RDN lowers ambulatory and office blood pressure (BP) to a significantly greater extent than sham treatment. BP-lowering efficacy is evident both in patients with and without concomitant antihypertensive medication. The average decrease of 10 mmHg in office BP is estimated to lower the incidence of cardiovascular events by 25-30%, based on meta-analyses of RCTs using pharmacological treatment. Neither peri-procedural, nor short-term or long-term adverse events or safety signals (available up to 3 years) have been observed. Implementing RDN as an innovative third option in the armamentarium of antihypertensive treatment requires a structured process that ensures the appropriate performance of the endovascular RDN procedure and adequate selection of hypertensive patients. The latter should also incorporate patients' perspective and preference that needs to be respected in a shared decision-making process.

Aims Resting heart rate (RHR) has been shown to be associated with cardiovascular outcomes in various conditions. It is unknown whether different levels of RHR and different associations with cardiovascular outcomes occur in patients with or without diabetes, because the impact of autonomic neuropathy on vascular vulnerability might be stronger in diabetes. Methods We examined 30 937 patients aged 55 years or older with a history of or at high risk for cardiovascular disease and and results after myocardial infarction, stroke, or with proven peripheral vascular disease from the ONTARGET and TRANSCEND trials investigating ramipril, telmisartan, and their combination followed for a median of 56 months. We analysed the association of mean achieved RHR on-treatment with the primary composite outcome of cardiovascular death, myocardial infarction, stroke, hospitalization for heart failure, the components of the composite primary outcome, and all-cause death as continuous and categorical variables. Data were analysed by Cox regression analysis, ANOVA, and v2 test. These trials were registered with ClinicalTrials.gov.number NCT00153101. Patients were recruited from 733 centres in 40 countries between 1 December 2001 and 31 July 2008 (ONTARGET) and 1 November 2001 until 30 May 2004 (TRANSCEND). In total, 19 450 patients without diabetes and 11 487 patients with diabetes were stratified by mean RHR. Patients with diabetes compared to no diabetes had higher RHRs (71.8 ± 9.0 vs. 67.9 ± 8.8, P < 0.0001). In the categories of <60 bpm, 60 <_ 65 bpm, 65 <_ 70 bpm, 70 <_ 75 bpm, 75 <_ 80 bpm and >_80 bpm, non-diabetic patients had an increased hazard of the primary outcome with mean RHR of 75 <_ 80 bpm (adjusted hazard ratio [HR] 1.17 (1.01–1.36)) compared to RHR 60 <_ 65 bpm. For patients with in-trial RHR >_80 bpm the hazard ratios were highest (diabetes: 1.96 (1.64–2.34), no diabetes: 1.73 (1.49–2.00), For cardiovascular death hazards were also clea

Three recent renal denervation studies in both drug-naïve and drug-treated hypertensive patients demonstrated a significant reduction of ambulatory blood pressure compared with respective sham control groups. Improved trial design, selection of relevant patient cohorts, and optimized interventional procedures have likely contributed to these positive findings. However, substantial variability in the blood pressure response to renal denervation can still be observed and remains a challenging and important problem. The International Sympathetic Nervous System Summit was convened to bring together experts in both experimental and clinical medicine to discuss the current evidence base, novel developments in our understanding of neural interplay, procedural aspects, monitoring of technical success, and others. Identification of relevant trends in the field and initiation of tailored and combined experimental and clinical research efforts will help to address remaining questions and provide much-needed evidence to guide clinical use of renal denervation for hypertension treatment and other potential indications.

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 56months 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 10mg daily, telmisartan 80mg daily, or the combination of both. Patients in TRANSCEND were ACE intolerant and randomized to telmisartan 80mg 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 ≥160mmHg 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 <140mmHg], with similar findings for all other endpoints in patients with diabetes, and for MI and stroke in patients without diabetes. In-trial SBP <120mmHg was associated with increased risk for the combined outcome in patients with dia