Effect of Alcohol-Mediated Renal Denervation on Blood Pressure in the Presence of Antihypertensive Medications: Primary Results from the TARGET BP I Randomized Clinical Trial.

BACKGROUND: Renal denervation (RDN) has demonstrated clinically relevant reductions in blood pressure among individuals with uncontrolled hypertension despite lifestyle intervention and medications. The safety and effectiveness of alcohol-mediated RDN has not been formally studied in this indication. METHODS: TARGET BP I is a prospective, international, sham-controlled, randomized, patient- and assessor-blinded trial investigating the safety and efficacy of alcohol-mediated RDN. Patients with office systolic blood pressure (SBP) ≥150 and ≤180 mmHg, office diastolic BP ≥90 mmHg and mean 24-hour ambulatory SBP ≥135 and ≤170 mmHg, despite prescription of 2-5 antihypertensive medications were enrolled. The primary endpoint was the baseline-adjusted change in mean 24-hour ambulatory systolic BP at 3 months post procedure. Secondary endpoints include mean between-group differences in office and ambulatory BP at additional time points. RESULTS: Among 301 patients randomized 1:1 to RDN or sham control, RDN was associated with a significant reduction in 24-hour ambulatory SBP at 3 months (mean ± standard deviation -10.0 ± 14.2 mmHg versus -6.8 ± 12.1 mmHg, treatment difference -3.2 mmHg, 95% confidence interval [CI] -6.3, 0.0 mmHg; P=0.0487). Subgroup analysis of the primary endpoint revealed no significant interaction across predefined subgroups. At 3 months, the mean change in office SBP was -12.7 ± 18.3 mmHg and -9.7 ± 17.3 mmHg (difference, -3.0, 95% CI -7.0, 1.0; P=0.173), for RDN and sham, respectively. No significant differences in ambulatory or office diastolic BP were observed. Adverse safety events through 6 months were uncommon with 1 instance of accessory renal artery dissection in the RDN group (0.7%). No significant between-group differences in medication changes or patient adherence were identified. CONCLUSIONS: Alcohol-mediated RDN was associated with a modest but statistically significant reduction in 24-hour ambulatory systolic BP compared with sham control. No significant differences between groups in office BP or 6-month major adverse events were observed.

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

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

Overview of the Evolution of Hypertension: From Ancient Chinese Emperors to Today.

Hypertension is one of the most commonly treated conditions in modern medical practice, but despite its long history, it was largely ignored until the midpoint of the 20th century. This article will review the origins of elevated blood pressure from when it was first appreciated in 2600 BC to its most recent emerging treatments. Awareness of sustained elevations in blood pressure goes back to the Chinese Yellow Emperor's Classic of Internal Medicine (2600 BC); even then, salt was appreciated as a contributor to elevated pressure. Early treatments included acupuncture, venesection, and bleeding by leeches. About 1000 years later, the association between the palpated pulse and the development of heart and brain diseases was described by Ebers Papyrus (1550 BC). But really, it has only been since well after World War II that hypertension has finally been appreciated as the cause of so much heart, stroke, and kidney disease. We review the development of effective treatments for hypertension while acknowledging that so many people with hypertension in need of treatment have unacceptably poor blood pressure control. We explore why, despite our considerable and growing knowledge of hypertension, it remains a significant public health problem globally.

Impact of Antihypertensive Medication Changes After Renal Denervation Among Different Patient Groups: SPYRAL HTN-ON MED.

BACKGROUND: The SPYRAL HTN-ON 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)trial showed significant office and nighttime systolic blood pressure (BP) reductions in patients with hypertension following renal denervation (RDN) compared with sham-control patients, despite similar 24-hour BP reductions. We compared antihypertensive medication and BP changes among prespecified subpopulations. METHODS: The multicenter, randomized, sham-controlled, blinded SPYRAL HTN-ON MED trial (n=337) evaluated BP changes after RDN compared with a sham procedure in patients with hypertension prescribed 1 to 3 antihypertensive drugs. Most patients (n=187; 54%) were enrolled outside the United States, while 156 (46%) US patients were enrolled, including 60 (18%) Black Americans. RESULTS: Changes in detected antihypertensive drugs were similar between RDN and sham group patients in the outside US cohort, while drug increases were significantly more common in the US sham group compared with the RDN group. Patients from outside the United States showed significant reductions in office and 24-hour mean systolic BP at 6 months compared with the sham group, whereas BP changes were similar between RDN and sham in the US cohort. Within the US patient cohort, Black Americans in the sham control group had significant increases in medication burden from baseline through 6 months (P=0.003) but not in the RDN group (P=0.44). CONCLUSIONS: Patients enrolled outside the United States had minimal antihypertensive medication changes between treatment groups and had significant office and 24-hour BP reductions compared with the sham group. Increased antihypertensive drug burden in the US sham cohort, especially among Black Americans, may have diluted the treatment effect in the combined trial population. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02439775.

Patient-Level Pooled Analysis of Endovascular Ultrasound Renal Denervation or a Sham Procedure 6 Months After Medication Escalation: The RADIANCE Clinical Trial Program.

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.

Safety and Efficacy of Renal Denervation in Patients Taking Antihypertensive Medications.

BACKGROUND: Renal denervation (RDN) reduces blood pressure (BP) in patients with uncontrolled hypertension in the absence of antihypertensive medications. OBJECTIVES: This trial assessed the safety and efficacy of RDN in the presence of antihypertensive medications. METHODS: SPYRAL 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. RESULTS: The 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. CONCLUSIONS: There 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).

A Plain Language Summary on the Effect of the Medication Vibegron on Blood Pressure and Heart Rate in People With Overactive Bladder.

WHAT IS THIS SUMMARY ABOUT?: This is a plain language summary of an article originally published in the journal Blood Pressure Monitoring. Vibegron is a medicine that was approved by the US Food and Drug Administration (also called FDA) in 2020 for treatment of overactive bladder, a condition that causes a frequent and urgent need to urinate. This study took place before the medicine was approved to look at whether vibegron affects blood pressure or heart rate. WHAT WERE THE RESULTS?: A total of 214 patients with overactive bladder took part in the study. 108 patients took vibegron for 28 days, and 106 took placebo for 28 days. A placebo is a pill with no medicine in it. Their blood pressure was measured on the first day and the last day. A meaningful increase in blood pressure is when a patient's average blood pressure measurements changed by 3.5 mmHg or more. Patients with overactive bladder who took a 75 mg dose of vibegron once daily had no meaningful increase in blood pressure or heart rate. This included people who were already taking medication for their high blood pressure. WHAT DO THE RESULTS MEAN?: This study suggests that patients can use vibegron without concern that it may meaningfully raise blood pressure or heart rate.

OECD indicator 'AMI 30-day mortality' is neither comparable between countries nor suitable as indicator for quality of acute care.

BACKGROUND: Hospital mortality after acute myocardial infarction (AMI, ICD-10: I21-I22) is used as OECD indicator of the quality of acute care. The reported AMI hospital mortality in Germany is more than twice as high as in the Netherlands or Scandinavia. Yet, in Europe, Germany ranks high in health spending and availability of cardiac procedures. We provide insights into this contradictory situation. METHODS: Information was collected on possible factors causing the reported differences in AMI mortality such as prevalence of risk factors or comorbidities, guideline conform treatment, patient registration, and health system structures of European countries. International experts were interviewed. Data on OECD indicators 'AMI 30-day mortality using unlinked data' and 'average length of stay after AMI' were used to describe the association between these variables graphically and by linear regression. RESULTS: Differences in prevalence of risk factors or comorbidities or in guideline conform acute care account only to a smaller extent for the reported differences in AMI hospital mortality. It is influenced mainly by patient registration rules and organization of health care. Non-reporting of day cases as patients and centralization of AMI care-with more frequent inter-hospital patient transfers-artificially lead to lower calculated hospital mortality. Frequency of patient transfers and national reimbursement policies affect the average length of stay in hospital which is strongly associated with AMI hospital mortality (adj R2 = 0.56). AMI mortality reported from registries is distorted by different underlying populations. CONCLUSION: Most of the variation in AMI hospital mortality is explained by differences in patient registration and organization of care instead of differences in quality of care, which hinders cross-country comparisons of AMI mortality. Europe-wide sentinel regions with comparable registries are necessary to compare (acute) care after myocardial infarction.

Durability of the Blood Pressure Effects of Renal Pelvis Denervation in Patients with Hypertension During a 12-Month Observation.

INTRODUCTION: We previously completed a trial of renal pelvic denervation for treating hypertension that reduced blood pressure by the 2-month primary endpoint. However, information on the durability of effectiveness is a critical requirement for device therapy and we now report data up to 12 months. METHODS: This was an open label single-arm feasibility study in patients with increased blood pressure despite taking an average of 2.7 medications. The key endpoint reported here was ambulatory blood pressure at 12 months following renal pelvic denervation. RESULTS: In the 17 patients (mean age 56) studied, there was a reduction from the baseline of 148 + 8.7 mmHg in the primary endpoint of mean daytime systolic blood pressure at 12 months of 19.1 (26.7, 11.6) mmHg, P<0.001, as compared with the 2-month result of 19.4 (24.9, 14.0) mmHg. The 24-hour systolic blood pressure fell by 19.3 (26.7, 11.9), P<0.001, and nighttime systolic fell by 18.7 (27.5, 9.8), P<0.001, mmHg at 12 months. Diastolic pressures also fell significantly from baseline at 12 months. As well, automated office systolic blood pressure was reduced from the baseline of 156.5 + 12.3 by 24.8 (33.2. 16.8) mmHg, P<0.001, at 12 months as compared with 22.4 (31.5, 13.3) at 2-months. . All blood pressure changes at 12 months were not different from those at 2 months, thus confirming the durability of the procedure. There were no serious procedural, clinical or laboratory adverse events related to the intervention. Serum creatinine fell from 1.03 + 0.22 to 0.82 + 0.16 mg/dl and estimated glomerular filtration rate rose from 79.6 + 17.8 to 96.3 + 16.4 ml/min/1.73m2 by 12 months, again sustaining effects seen at 2 months. DISCUSSION/CONCLUSION: These findings provide evidence that the significant blood pressure-lowering effects of renal pelvis denervation are durable and safe for at least one year and provide the basis for a pivotal randomized blinded trial to further define the safety and effectiveness of this procedure.

Alcohol-mediated renal denervation in patients with hypertension in the absence of antihypertensive medications.

BACKGROUND: Ultrasound and radiofrequency renal denervation (RDN) have been shown to safely lower blood pressure (BP) in hypertension. AIMS: The TARGET BP OFF-MED trial investigated the efficacy and safety of alcohol-mediated renal denervation (RDN) in the absence of antihypertensive medications. METHODS: This randomised, blinded, sham-controlled trial was conducted in 25 centres in Europe and the USA. Patients with a 24-hour systolic BP of 135-170 mmHg, an office systolic BP 140-180 mmHg and diastolic BP ≥90 mmHg on 0-2 antihypertensive medications were enrolled. The primary efficacy endpoint was the change in mean 24-hour systolic BP at 8 weeks. Safety endpoints included major adverse events up to 30 days. RESULTS: A total of 106 patients were randomised; the baseline mean office BP following medication washout was 159.4/100.4±10.9/7.0 mmHg (RDN) and 160.1/98.3±11.0/6.1 mmHg (sham), respectively. At 8 weeks post-procedure, the mean (±standard deviation) 24-hour systolic BP change was â2.9±7.4 mmHg (p=0.009) versus â1.4±8.6 mmHg (p=0.25) in the RDN and sham groups, respectively (mean between-group difference: 1.5 mmHg; p=0.27). There were no differences in safety events between groups. After 12 months of blinded follow-up, with medication escalation, patients achieved similar office systolic BP (RDN: 147.9±18.5 mmHg; sham: 147.8±15.1 mmHg; p=0.68) with a significantly lower medication burden in the RDN group (mean daily defined dose: 1.5±1.5 vs 2.3±1.7; p=0.017). CONCLUSIONS: In this trial, alcohol-mediated RDN was delivered safely but was not associated with significant BP differences between groups. Medication burden was lower in the RDN group up to 12 months.

Middle-Aged and Older Patients With Left Ventricular Hypertrophy: Higher Mortality With Drug Treated Systolic Blood Pressure Below 130 mm Hg.

BACKGROUND: Approximately 40% of people with hypertension have left ventricular hypertrophy (LVH) detected by ECG or echocardiography. Because patients with LVH have poor myocardial microcirculation, they may be too sensitive to lowering systolic blood pressure (SBP) too much due to a lack of myocardial perfusion pressure. We aimed to investigate whether the average achieved SBP <130 mm Hg may cause harm in patients with LVH in the Valsartan Antihypertensive Long-Term Use Evaluation trial (VALUE). METHODS: Of the 15 245 VALUE participants, we identified 13 803 patients without cardiovascular events during the first 6 months after randomization. Of these, 2458 patients had electrocardiographic LVH (ECG-LVH). Cox analyses adjusted for age, gender, and baseline variables compared cardiac and all-cause mortality and other prespecified end points for patients who achieved average SBP 130 to 139 mm Hg (No-LVH group n=4863; ECG-LVH group n=929) and <130 mm Hg (No-LVH group n=2107; ECG-LVH group n=305). Reference groups were patients who achieved average SBP ≥140 mm Hg following the first excluded 6 months (No-LVH group n=4375; ECG-LVH group n=1224). RESULTS: The No-LVH group achieving average SBP <130 mm Hg had a significantly lower incidence of several cardiovascular end points. The ECG-LVH group achieving average SBP <130 mm Hg had higher cardiac mortality (hazard ratio, 1.98 [95% CIs, 1.06-3.70]; P=0.032) and all-cause mortality (hazard ratio, 1.74 [95% CIs, 1.17-2.60]; P=0.007), and SBP <130 mm Hg was not associated with a reduction in any end point. CONCLUSIONS: Our findings may be seen as a signal that caution is warranted when treating middle-aged and older patients with electrocardiographic or echocardiographic LVH to SBP <130 mm Hg.

Endovascular Ultrasound Renal Denervation to Treat Hypertension: The RADIANCE II Randomized Clinical Trial.

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.

Patient-Level Pooled Analysis of Ultrasound Renal Denervation in the Sham-Controlled RADIANCE II, RADIANCE-HTN SOLO, and RADIANCE-HTN TRIO Trials.

Importance: Ultrasound renal denervation (uRDN) was shown to lower blood pressure (BP) in patients with uncontrolled hypertension (HTN). Establishing the magnitude and consistency of the uRDN effect across the HTN spectrum is clinically important. Objective: To characterize the effectiveness and safety of uRDN vs a sham procedure from individual patient-level pooled data across uRDN trials including either patients with mild to moderate HTN on a background of no medications or with HTN resistant to standardized triple-combination therapy. Data Sources: A Study of the ReCor Medical Paradise System in Clinical Hypertension (RADIANCE-HTN SOLO and TRIO) and A Study of the ReCor Medical Paradise System in Stage II Hypertension (RADIANCE II) trials. Study Selection: Trials with similar designs, standardized operational implementation (medication standardization and blinding of both patients and physicians to treatment assignment), and follow-up. Data Extraction and Synthesis: Pooled analysis using individual patient-level data using linear regression models to compare uRDN with sham across the trials. Main Outcomes and Measures: The primary outcome was baseline-adjusted change in 2-month daytime ambulatory systolic BP (dASBP) between groups. Results: A total of 506 patients were randomized in the 3 studies (uRDN, 293; sham, 213; mean [SD] age, 54.1 [9.3]; 354 male [70.0%]). After a 1-month medication stabilization period, dASBP was similar between the groups (mean [SD], uRDN, 150.3 [9.2] mm Hg; sham, 150.8 [10.5] mm Hg). At 2 months, dASBP decreased by 8.5 mm Hg to mean (SD) 141.8 (13.8) mm Hg among patients treated with uRDN and by 2.9 mm Hg to 147.9 (14.6) mm Hg among patients treated with a sham procedure (mean difference, -5.9; 95% CI, -8.1 to -3.8 mm Hg; P < .001 in favor of uRDN). BP decreases from baseline with uRDN vs sham were consistent across trials and across BP parameters (office SBP: -10.4 mm Hg vs -3.4 mm Hg; mean difference, -6.4 mm Hg; 95% CI, -9.1 to -3.6 mm Hg; home SBP: -8.4 mm Hg vs -1.4 mm Hg; mean difference, -6.8 mm Hg; 95% CI, -8.7 to -4.9 mm Hg, respectively). The BP reductions with uRDN vs sham were consistent across prespecified subgroups. Independent predictors of a larger BP response to uRDN were higher baseline BP and heart rate and the presence of orthostatic hypertension. No differences in early safety end points were observed between groups. Conclusions and Relevance: Results of this patient-level pooled analysis suggest that BP reductions with uRDN were consistent across HTN severity in sham-controlled trials designed with a 2-month primary end point to standardize medications across randomized groups. Trial Registration: ClinicalTrials.gov Identifier: NCT02649426 and NCT03614260.

Long-term reduction in morning and nighttime blood pressure after renal denervation: 36-month results from SPYRAL HTN-ON MED trial.

Elevated morning and nighttime blood pressures (BP) are associated with increased risk of cardiovascular events such as stroke and myocardial infarction. We compared the long-term changes in morning and nighttime BP in patients with uncontrolled hypertension (office systolic BP between 150 and <180 mmHg/diastolic BP ≥ 90 mmHg; mean ambulatory systolic BP (SBP) between 140 and <170 mmHg; 1-3 prescribed antihypertensive medications). Eighty patients were randomized to RDN or sham control. In patients taking at least 3 antihypertensive medications at 36 months (N = 23 RDN group; N = 23 sham group), the 24 h ambulatory SBP as well as morning (7:00-9:00AM) and nighttime (1:00-6:00AM) ambulatory SBP were significantly lower for the RDN group compared to sham control (24 h SBP: -20.2 vs. -10.2, p = 0.0087; morning SBP: -23.9 vs. -8.0 mmHg, p = 0.029; nighttime SBP: -20.8 vs. -7.2 mmHg, p = 0.0011). At 36 months, 24 h SBP was controlled to <130 mmHg in 40% of RDN patients in the morning compared to 6% for the sham group; P = 0.021 and in 80% of the RDN patients at night compared to 39% in the sham group; P = 0.019. Major adverse events through 36 months were rare in both groups, and there were no renal artery re-interventions or vascular complications. Morning and nighttime SBP were significantly lower in patients prescribed at least 3 antihypertensive medications at 36 months in the SPYRAL HTN-ON MED trial for RDN compared with sham control. The results suggest RDN has significant benefit when the risk of cardiovascular events is highest.

Patient Preferences for Pharmaceutical and Device-Based Treatments for Uncontrolled Hypertension: Discrete Choice Experiment.

BACKGROUND: Discrete choice experiment is a survey method used to understand how individuals make decisions and to quantify the relative importance of features. Using discrete choice experiment methods, we quantified patient benefit-risk preferences for hypertension treatments, including pharmaceutical and interventional treatments, like renal denervation. METHODS: Respondents from the United States with physician-confirmed uncontrolled hypertension selected between treatments involving a procedure or pills, using a structured survey. Treatment features included interventional, noninterventional, or no hypertension treatment; number of daily blood pressure (BP) pills; expected reduction in office systolic BP; duration of effect; and risks of drug side effects, access site pain, or vascular injury. The results of a random-parameters logit model were used to estimate the importance of each treatment attribute. RESULTS: Among 400 patients completing the survey between 2020 and 2021, demographics included: 52% women, mean age 59.2±13.0 years, systolic BP 155.1±12.3 mm Hg, and 1.8±0.9 prescribed antihypertensive medications. Reduction in office systolic BP was the most important treatment attribute. The remaining attributes, in decreasing order, were duration of effect, whether treatment was interventional, number of daily pills, risk of vascular injury, and risk of drug side effects. Risk of access site pain did not influence choice. In general, respondents preferred noninterventional over interventional treatments, yet only a 2.3 mm Hg reduction in office systolic BP was required to offset this preference. Small reductions in office systolic BP would offset risks of vascular injury or drug side effects. At least a 20% risk of vascular injury or drug side effects would be tolerated in exchange for improved BP. CONCLUSIONS: Reduction in systolic BP was identified as the most important driver of patient treatment preference, while treatment-related risks had less influence. The results indicate that respondents would accept interventional treatments in exchange for modest reductions in systolic BP compared with those observed in renal denervation trials.

Hypertension management in patients with cardiovascular comorbidities.

Arterial hypertension is a leading cause of death globally. Due to ageing, the rising incidence of obesity, and socioeconomic and environmental changes, its incidence increases worldwide. Hypertension commonly coexists with Type 2 diabetes, obesity, dyslipidaemia, sedentary lifestyle, and smoking leading to risk amplification. Blood pressure lowering by lifestyle modifications and antihypertensive drugs reduce cardiovascular (CV) morbidity and mortality. Guidelines recommend dual- and triple-combination therapies using renin-angiotensin system blockers, calcium channel blockers, and/or a diuretic. Comorbidities often complicate management. New drugs such as angiotensin receptor-neprilysin inhibitors, sodium-glucose cotransporter 2 inhibitors, glucagon-like peptide-1 receptor agonists, and non-steroidal mineralocorticoid receptor antagonists improve CV and renal outcomes. Catheter-based renal denervation could offer an alternative treatment option in comorbid hypertension associated with increased sympathetic nerve activity. This review summarises the latest clinical evidence for managing hypertension with CV comorbidities.