Office Systolic Blood Pressure Reduction Research Articles

Smartphone application-based intervention to lower blood pressure: a systematic review and meta-analysis.

Nowadays, the mHealth market is flooded with smartphone applications (apps) lacking validation for blood pressure (BP)-lowering effects and BP measurement accuracy. This systematic review for Guidelines for BP control using digital technologies of the Japanese Society of Hypertension aimed to assess the validation studies of apps. We searched eligible studies in Ovid MEDLINE, Cochrane Library, and Ichushi, focusing on randomized controlled trials and observational studies comparing the effects of smartphone app-based interventions with non-digital healthcare. Random effects models of meta-analysis were employed to estimate the pooled effects of mean BP change and 95% confidence intervals (CIs). Out of 7385 studies screened, 76 studies with 46,459 participants were included. The interventions were significantly associated with a reduction in office systolic and diastolic BP at six months (systolic BP, -2.76 mmHg, 95% CI: -3.94 to -1.58; diastolic BP, -1.23 mmHg, -1.80 to -0.67). Normotensives saw a significant reduction in office systolic BP at three-month (-4.44 mmHg, -6.96 to -1.92), diminishing afterward (six-month, 0.86 mmHg, -2.81 to 4.52; twelve-month, 0.86 mmHg, -2.81 to 4.52). Conversely, hypertensive participants experienced a significant reduction in office systolic BP at both three- and six-month (three-month, -7.71 mmHg, -10.63 to -4.79; six-month, -1.88 mmHg, -3.41 to -0.35), albeit with limited evidence thereafter. A larger BP reduction was observed among participants using apps with wireless transmission of BP measurements (P = 0.047 for interaction), while there was no clear difference in BP reduction according to the presence of other functions. Smartphone app-based interventions may hold the potential to improve BP levels.

Effects of Catheter-Based Renal Denervation in Hypertension: A Systematic Review and Meta-Analysis.

Several sham-controlled trials have investigated the efficacy and safety of catheter-based renal denervation (RDN) with mixed outcomes. We aimed to perform a comprehensive meta-analysis of all randomized, sham-controlled trials investigating RDN with first- and second-generation devices in hypertension. We searched MEDLINE and the Cochrane Library for eligible trials. Outcomes included both efficacy (24-hour and office systolic [SBP] and diastolic blood pressure [DBP]) and safety (all-cause death, vascular complication, renal artery stenosis >70%, hypertensive crisis) of RDN. We performed a study-level, pairwise, random-effects meta-analysis of the summary data. Ten trials comprising 2478 patients with hypertension while being either off or on treatment were included. Compared with sham, RDN reduced 24-hour and office systolic blood pressure by 4.4 mm Hg (95% CI, 2.7 to 6.1; P<0.00001) and 6.6 mm Hg (95% CI, 3.6 to 9.7; P<0.0001), respectively. The 24-hour and office diastolic blood pressure paralleled these findings (-2.6 mm Hg [95% CI, -3.6 to -1.5]; P<0.00001; -3.5 mm Hg [95% CI, -5.4 to -1.6]; P=0.0003). There was no difference in 24-hour and office systolic blood pressure reduction between trials with and without concomitant antihypertensive medication (P for interaction, 0.62 and 0.73, respectively). There was no relevant difference in vascular complications (odds ratio, 1.69 [95% CI, 0.57 to 5.0]; P=0.34), renal artery stenosis (odds ratio, 1.50 [95% CI, 0.06 to 36.97]; P=0.80), hypertensive crisis (odds ratio, 0.65 [95% CI, 0.30 to 1.38]; P=0.26), and all-cause death (odds ratio, 1.76 [95% CI, 0.34 to 9.20]; P=0.50) between RDN and sham groups. Change of renal function based on estimated glomerular filtration rate was comparable between groups (P for interaction, 0.84). There was significant heterogeneity between trials. RDN safely reduces ambulatory and office systolic blood pressure/diastolic blood pressure versus a sham procedure in the presence and absence of antihypertensive medications.

O50 EFFECT OF LONG-TERM USE OF CONTINUOUS POSITIVE AIRWAY PRESSURE ON BLOOD PRESSURE PATIENTS WITH RESISTANT HYPERTENSION AND OBSTRUCTIVE SLEEP APNEA

Background and Objective: Obstructive Sleep Apnea (OSA) is strongly associated with Resistant Hypertension (RHT). Continuous positive airway pressure (CPAP) is the treatment of choice for moderate-severe OSA. Its benefit in terms of blood pressure (BP) control is still unclear. The objective of the study is to evaluate the effect of CPAP on BP in patients with RHT and moderate-severe OSA. Methods: This was a prospective intervention study that included 124 patients with RHT and moderate/severe OSA (AHI&gt;15/hour) divided in 2 groups. Patients using CPAP uninterruptedly for a minimum period of 12 months (CPAP group) were compared with those who refused to use CPAP despite clinical indication (Control group). Office BP and 24-hour ABPM were obtained at baseline and after follow-up. Primary outcomes were changes in office and ambulatory BPs, and nocturnal BP reduction. Results: 124 individuals were included (37.9% male with a mean age of 60.7 ± 7.8 years), 65 in the CPAP group and 59 in the control group with a median [interquartile range] follow-up time of 68 [49-81] months. There was a reduction in office systolic BP (SBP) of -7.5 mmHg ([CI95%: -16.3 to -1.1],p=0.089), in nocturnal SBP and diastolic BP (DBP) of – 6.1 mmHg ([CI95%: -12.4 to 0.3],p=0.06) and -3.5 mmHg ([CI95%: -7.4 to 0.6],p=0.092), respectively, without reaching statistical significance. Otherwise, after excluding 9 patients of CPAP group with low adherence, we found a reduction in office SBP of -10.3 mmHg ([CI95%: -19.7 to 0.9],p=0.031), in 24-hour SBP and DBP of – 4.8 mmHg ([CI95%: -10.5 to 0.8],p=0.095) and -3.4 mmHg ([CI95%: -6.8 to 0.1],p=0.045), and in nocturnal SBP and DBP of – 8.1 mmHg ([CI95%: -14.7 to -1.5],p=0.017) and -5.3 mmHg ([CI95%: -9.6 to -1.1],p=0.014), respectively. Conclusion: Long term use of CPAP reduced office, 24-hour and nighttime SBP specially in resistant hypertensives with good CPAP adherence.

HIGHER BASELINE SYSTOLIC BLOOD PRESSURE IS ASSOCIATED WITH GREATER BLOOD PRESSURE REDUCTIONS FOLLOWING RADIOFREQUENCY RENAL DENERVATION IN A POOLED COHORT OF OVER 3900 PATIENTS

Objective: Uncontrolled hypertension (HTN) is the leading global risk factor for cardiovascular disease, and higher systolic blood pressure (SBP) increases this risk. Radiofrequency renal denervation (RF RDN) has been shown to reduce BP effectively in patients with uncontrolled HTN. We investigated the relationship between increasing baseline SBP and its change after RF RDN. Design and method: Patients undergoing RF RDN (N=3974) were pooled from global clinical trials in patients on antihypertensive drugs: SPYRAL First-In-Man, SYMPLICITY HTN-3, HTN-Japan, SPYRAL HTN ON-MED, and the Global SYMPLICITY Registry DEFINE. Office and 24-h ambulatory SBP at baseline and 6 months after RF RDN were evaluated. Linear regression analysis was performed to evaluate the correlation between baseline and SBP change after 6 months (SBP change=intercept+slope∗baseline SBP). Results: The baseline SBP for office and 24-h ambulatory BP were 167±24mmHg and 154±18mmHg, respectively. Patients were prescribed 4.4±1.5 antihypertensive drugs at baseline. After 6 months, prescribed antihypertensive drugs decreased to 4.3±1.5 (p&lt;0.0001). In both office and 24-h ambulatory SBP, baseline SBP correlation with SBP change after 6 months was statistically significant; every 1mmHg increase in baseline office SBP was associated with a 0.59mmHg (r2=0.30; p&lt;0.001) reduction in SBP, and every 1mmHg increase in baseline 24-h ambulatory SBP was associated with a 0.45mmHg (r2=0.19; p&lt;0.001) reduction in SBP at 6 months. According to this linear regression, a baseline office SBP of 160mmHg, 170mmHg and 180mmHg were associated with 6 months office SBP reduction by -9.2mmHg, -15.1mmHg and -21.0mmHg, respectively (Figure). Reductions in SBP of this magnitude have previously been shown to correspond with substantial reductions in the risk of cardiovascular events. Conclusions: A continuous and inverse relationship was observed between baseline SBP and 6 months SBP change in patients with uncontrolled HTN undergoing RF RDN. Higher baseline SBP led to a greater reduction in SBP and may derive greater benefit from an RDN procedure. These findings may help clinicians and patients in their shared decision making regarding their BP management. However, this is a retrospective analysis which needs further prospective validation.

Cost Effectiveness of Endovascular Ultrasound Renal Denervation in Patients with Resistant Hypertension.

Resistant hypertension (rHTN) is defined as blood pressure (BP) of ≥ 140/90mmHg despite treatment with at least three antihypertensive medications, including a diuretic. Endovascular ultrasound renal denervation (uRDN) aims to control BP alongside conventional BP treatment with antihypertensive medication. This analysis assesses the cost effectiveness of the addition of the Paradise uRDN System compared with standard of care alone in patients with rHTN from the perspective of the United Kingdom (UK) health care system. Using RADIANCE-HTN TRIO trial data, we developed a state-transition model. Baseline risk was calculated using Framingham and Prospective Cardiovascular Münster (PROCAM) risk equations to estimate the long-term cardiovascular risks in patients treated with the Paradise uRDN System, based on the observed systolic BP (SBP) reduction following uRDN. Relative risks sourced from a meta-analysis of randomised controlled trials were then used to project cardiovascular events in patients with baseline SBP ('control' patients); utility and mortality inputs and costs were derived from UK data. Costs and outcomes were discounted at 3.5% per annum. Modelled outcomes were validated against trial meta-analyses and the QRISK3 algorithm and real-world evidence of RDN effectiveness. One-way and probabilistic sensitivity analyses were conducted to assess the uncertainty surrounding the model inputs and sensitivity of the model results to changes in parameter inputs. Results were reported as incremental cost-effectiveness ratios (ICERs). A mean reduction in office SBP of 8.5mmHg with uRDN resulted in an average improvement in both absolute life-years (LYs) and quality-adjusted life-years (QALYs) gained compared with standard of care alone (0.73 LYs and 0.67 QALYs). The overall base-case ICER with uRDN was estimated at £5600 (€6500) per QALY gained (95% confidence interval £5463-£5739 [€6341-€6661]); modelling demonstrated > 99% probability that the ICER is below the £20,000-£30,000 (€23,214-€34,821) per QALYs gained willingness-to-pay threshold in the UK. Results were consistent across sensitivity analyses and validation checks. Endovascular ultrasound RDN with the Paradise system offers patients with rHTN, clinicians, and healthcare systems a cost-effective treatment option alongside antihypertensive medication.

Safety and Efficacy of Renal Denervation in Patients Taking Antihypertensive Medications

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

Efficacy and safety of Qiangli Dingxuan tablet combined with amlodipine besylate for essential hypertension: a randomized, double-blind, placebo-controlled, parallel-group, multicenter trial.

Background: Hypertension, a major cardiovascular risk factor, severely impacts patients' quality of life. Qiangli Dingxuan tablet (QDT) is a formally approved Chinese patent medicine, which has been widely used as an adjunctive treatment for hypertension. This study aimed to investigate the antihypertensive efficacy and safety of QDT combined with amlodipine besylate in patients with essential hypertension. Methods: In this randomized, double-blind, placebo-controlled, parallel-group, multicenter trial conducted in China, patients diagnosed with grade 1 to 2 essential hypertension were randomly assigned in a 1:1 to the treatment of QDT or placebo for 12weeks, alongside their ongoing treatment with amlodipine besylate. The primary outcome was the change in office blood pressure (BP) from baseline to 12weeks. In addition, safety analysis included the assessment of vital signs and laboratory values. Results: At baseline, 269 patients were randomly assigned to the QDT group (n = 133) or the placebo group (n = 136), and there were no significant differences in baseline characteristics between the two groups. The primary outcome based on the full analysis set from baseline to 12weeks showed that the mean difference in the change of office systolic BP reduction between the two groups was 6.86mmHg (95%CI, 4.84 to 8.88, p < 0.0001), for office diastolic BP, the mean difference in the change of office diastolic BP reduction between the two groups was 4.64mmHg (95%CI, 3.10 to 6.18, p < 0.0001). In addition, traditional Chinese medicine symptom scores were significantly decreased in the QDT group compared with the placebo group. No severe adverse events attributable to QDT were reported. Conclusion: The combination of QDT and amlodipine besylate demonstrates superior efficacy compared to amlodipine besylate monotherapy in the management of essential hypertension. QDT shows potential as an adjunctive treatment for essential hypertension. However, further rigorous clinical trials are warranted to validate these findings. Clinical Trial Registration: [https://clinicaltrials.gov/study/NCT05521282?cond=NCT05521282&rank=1]; Identifier: [NCT05521282].

PHARMACOGENOMICS-GUIDED DRUG THERAPY FOR HYPERTENSION

Objective: The hypertension control rate is only 16.8% in China, and superior reasonable treatment is contributive to improve the rate. This study is aimed to evaluate whether pharmacogenomics-guided drug therapy is superior to conventional therapy in lowering blood pressure. Design and method: DNA samples were collected from 93 hypertensive patients. All patients entered a 4-week conventional treatment period, and then entered a 4-week pharmacogenomics-guided drug therapy period (the antihypertensive regimen was adjusted according to the pharmacogenomic report). The hypertension control rate and reduction of blood pressure (BP) were analyzed. High-throughput targeted sequencing panel was designed to detect efficacy and adverse-related genes of 24 commonly used antihypertensive drugs (5 types) and 52 gene loci were analyzed related to drug Efficacy (E): “E-”, “E”, “E+”, Tolerance (T): “T-”, “T”, “T+” and Metabolic (M): “M-”, “M”, “M+”. Clinical drug administration was guided according to relevant judgement results. Results: Compared with the conventional therapy group, the hypertension control rate of office and home blood pressure in the precise treatment group increased by 14.75% and 25.81%, respectively. The reduction of BP in the precise treatment group was greater than conventional therapy group ( Table and Figure). Conclusions: Compared with conventional therapy, the pharmacogenomics-guided drug therapy can control blood pressure more effectively. Table. Comparison of Reduction in Office Systolic Blood Pressure (SBP)and Home SBP between the Precise Treatment Group and the Conventional Therapy Group Figure: Comparison of Reduction in Office SBP and Home SBP between the Precise Treatment Group and the Conventional Therapy Group

34. Efficacy and Safety of Sacubitril Valsartan in Managing Hypertension Compared with Angiotensin Receptor Blockers: A Systematic Review and Meta-analysis

Background: Sacubitril/Valsartan has shown promising result in the management of heart failure with reduced ejection fraction patients. However, it also withhold the potential as antihypertensive agent. Thus, its effectiveness in reducing high blood pressure (BP) compared with Angiotensin Receptor Blockers (ARBs) needs to be determined. Objective: This study aimed to compare the efficacy and safety of Sacubitril/Valsartan and ARBs in managing hypertension patients. Methods: We searched for the studies from Pubmed, Proquest, Google Scholar and Cochrane Library databases which compare the BP reduction effect of Sacubitril/Valsartan and ARBs. The main outcomes were mean office and ambulatory BP reduction. The safety profile was determined by the incidence of adverse events (AEs). Results: 5114 adult patients with hypertension from 10 RCTs were included. Sacubitril/Valsartan provided significant mean reduction of office systolic BP (mean difference: –4.66; 95%CI: –5.13 to –4.20; p &lt; 0.001), office diastolic BP (mean difference: –3.23; 95%CI: –3.54 to –2.92; p &lt; 0.001), ambulatory systolic BP (mean difference: –3.42; 95%CI: –5.13 to –1.17; p &lt; 0.001), and ambulatory diastolic BP compared with ARBs (mean difference: –1.50; 95%CI: –2.15 to –0.85; p &lt; 0.001). There was no significant difference in the incidence of AEs between the two groups (RR: 1.04; 95%CI: 0.95 to 1.14; p = 0.35). The BP reduction and incidence of AEs were consistent in the subgroup analysis (Olmesartan and Valsartan treatment group), except in comparison with Olmesartan treatment group for ambulatory systolic BP parameter (mean difference: –2.62; 95% CI: –5.30 to 0.07; p: 0.06). Conclusion: Sacubitril/Valsartan is more potent in reducing BP to ARBs, with similar safety profile.

Effect of renal denervation for patients with isolated systolic hypertension: a systematic review and meta-analysis.

Renal denervation (RDN) is a promising treatment based on catheter intervention for patients with refractory hypertension. However, the effect in patients with isolated systolic hypertension (ISH) remains controversial. The aim of this meta-analysis was to determine the blood pressure lowing effect of RDN in patients with ISH compared with combined systolic/diastolic hypertension (CH) patients. PubMed, Embase, Cochrane and ClinicalTrials.gov were searched for prospective clinical studies that included RDN. The outcomes of interest were the change of 24-hour ambulatory systolic blood pressure (SBP) from baseline. We used the fixed effects model to calculate weighted mean difference (WMD) with 95% confidence interval (CI). Six trials were included, with 1405 participants, including 597 patients with ISH and 808 patients with CH. Mean follow-up was five months. The reduction of 24-hour ambulatory SBP was significantly greater for the CH patients than the ISH patients (WMD = 3.89, 95% CI: 2.32-5.45, P < 0.0001). RDN also showed a greater reduction in office SBP in the CH patients compared to the ISH patients (WMD = 10.24, 95% CI: 4.24-15.74, P = 0.0003). And the effect was independent of age, length of follow-up, and ablation device. RDN provides superior blood pressure control in the CH patients compared with the ISH patients, and the CH patients may be the best suitable population for which RDN is indicated.

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

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. 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. 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. 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.

The potential of blood pressure telemonitoring: experience in the UK and Japan.

Hypertension is the most important and modifiable risk factor for cardiovascular disease (CVD) morbidity and mortality worldwide, and a growing issue as the global population with hypertension increases (estimated to be 626 million women and 652 million men in 2019, almost double the number in 1990). In addition, global control rates for hypertension remain poor: 23% for women and 18% for men in 2019 (Lancet. 2021:957). Measures to reduce the number of poorly controlled hypertensive patients are urgently needed. Remarkable advances in healthcare technology have changed healthcare delivery dramatically in the last decade with out-of-office blood pressure (BP) telemonitoring being widely used in clinical research (Hypertension. 2020:1368). We have demonstrated the efficacy of BP telemonitoring and digital intervention for the management of hypertension in the Telemonitoring And Self-Management IN the control of Hypertension (TASMINH) trials (Lancet. 2010:163, JAMA. 2014:799, Lancet. 2018:949), the Home and Online Management and Evaluation of Blood Pressure (HOME BP) trial (BMJ. 2021:m4858), and the HERB Digital Hypertension 1(HERB-DH1) pivotal trial (Eur Heart J. 2021:4111). A recent meta-analysis found that home BP telemonitoring improved office systolic BP (SBP) by 3.99 mmHg and home BP telemonitoring plus additional support (e.g., counselling and medications management) also showed a reduction of office SBP by 2.44 mmHg versus home BP telemonitoring alone (J Hum Hypertens. 2017:427). This evidence suggests that BP telemonitoring is an optimal tool for reducing BP levels and that combining BP telemonitoring and co-interventions would be the most effective approach for the management of hypertension. There are additional benefits from BP telemonitoring system in clinical practice, including assessment of accurate and reliable out-of-office BP data, and ease of BP measurement and recording by patients without the need for manual systems. Furthermore, such systems can reduce nonadherence of antihypertensive medications and clinical inertia, both of which contribute to a treatment-resistant hypertension (J Hypertens. 2017:2346, J Hypertens. 2021:1238). In practical terms, telemonitoring also facilitates optimal BP management for patients living in geographically remote or poorly medically resourced areas (Hypertension. 2021:1927). In this session, through discussion of the evidence base and clinical experience in the UK and Japan, we will examine the prospects of BP telemonitoring systems for the future management of hypertension. We will examine how BP telemonitoring systems are used and affect BP control in both clinical trials and subsequent implementation. In addition, by comparing such work in the UK and Japan, we will assess the potential of BP telemonitoring systems as a solution to the inadequate BP control status worldwide.

PATIENT PREFERENCES FOR PHARMACEUTICAL AND INTERVENTIONAL HYPERTENSION TREATMENTS: RESULTS FROM A DISCRETE CHOICE EXPERIMENT

Objective: To quantify patient benefit-risk preferences for interventional and pharmaceutical treatments for hypertension (HTN) using discrete choice experiment (DCE) methods. Design and method: A DCE is an established survey method commonly used to quantify preference for selected treatment attributes in hypothetical profiles, allowing estimation of tradeoffs that are acceptable when evaluating several attributes together. Respondents with physician confirmed uncontrolled HTN were presented with a series of questions with hypothetical HTN treatments with differing levels of treatment risk and benefit. Respondents could also choose no HTN treatment. A random parameters logit analysis of the survey treatment choices was used to estimate the relative preferences and importance for each attribute. Results: 400 patients completed the survey, with 52% female, mean age 59 ± 13 years, systolic blood pressure (BP) 155 ± 12 mmHg and 1.8 ± 0.9 average prescribed antihypertensive medications. Reduction in office systolic blood pressure (BP) was the most influential treatment attribute. The remaining attributes were less impactful on respondents’ treatment choice (i.e., duration of effect, whether treatment was interventional, number of daily pills, risk of vascular injury, risk of medication side effects, and risk of temporary pain and bruising). When given a choice between no HTN treatment and an interventional treatment with a 20% risk of procedure side effects, the likelihood of selecting the interventional treatment increased with the magnitude of blood pressure reduction. No more than a 2.5 mmHg reduction in office systolic BP was sufficient to offset treatment risks associated with an interventional procedure like RDN. Conclusions: Among U.S. patients with HTN, a DCE study demonstrated that BP reduction was the most important driver of choice, risks were less important, and a minimal BP reduction was sufficient to offset treatment risks associated with an interventional procedure like RDN.

Preprocedural features of patients under antihypertensive drugs may help identify responders to renal denervation: a hypothesis-generating study.

Renal denervation (RDN) is effective to lower systolic blood pressure (SBP) in essential hypertension. However, patient selection under medications remains an important unmet clinical need. This multicenter study aimed at observing whether preprocedural features associated with increased renin-angiotensin-aldosterone activity influence RDN response. This study enrolled the patients who underwent RDN for uncontrolled hypertension. Medical records were reviewd and patients were divided into 2 groups depending by meeting any of the following conditions prior to RDN: (1) >10 mmHg of office SBP reduction after aldosterone inhibition, (2) aldosterone-renin ratio >30 or (3) slow flow on the renal angiogram. RDN responders were defined by a reduction in 24-hour mean ≥6 mmHg or by ≥1 class of antihypertensive drug withdraw. A total of 46 patients were enrolled, of which 27 (59%) were in control group A and 19 (41%) in group B. The baseline age, gender, office and 24-hour SBP (mean 140.0 ± 12.8 mmHg vs. 144.0 ± 16.5 mmHg, p = 0.577) were comparable, while the number of prescribed drug classes was fewer in group A (4.0 ± 1.3 vs. 4.9 ± 0.9, p = 0.014). The proportion patients with prescribed aldosterone antagonist or high aldosterone-renin ratios were higher in group B. At 12 months post RDN, the results were significantly better in group B in terms of mean change in office SBP (12.4 ± 23.5 mmHg vs. 29.9 ± 25.5 mmHg, p = 0.046) and the proportion of RDN responders (51.9% vs. 89.5%, p < 0.001). RDN was more effective in patients with any of 3 clinical indices.

Application of win ratio methodology in the Global SYMPLICITY Registry for patients with atrial fibrillation or obstructive sleep apnea

Abstract Background/Introduction The win ratio is a new methodology which utilizes multiple hierarchical endpoints to evaluate clinical outcomes in trials. The win ratio may have added benefit in device therapy trials like renal denervation (RDN) where anti-hypertensive medication burden can influence blood pressure (BP) changes. Purpose In this analysis, we applied the win ratio to patients in the Global SYMPLICITY Registry (GSR) to quantify potential differences in RDN efficacy according to different comorbidities, specifically atrial fibrillation and obstructive sleep apnea. Methods All patients in GSR had an RDN procedure with the Symplicity Flex or Symplicity Spyral catheter. For the win ratio analysis, ambulatory systolic BP (ASBP) measurements, office systolic BP (OSBP) measurements and the number of prescribed anti-hypertensive medications at 6 months were included as hierarchical endpoints. Patients were divided into 1 of 2 groups: with or without atrial fibrillation (AF) at baseline. Each patient was compared with every other patient in the opposing group first according to ASBP to determine “win”, “lose” or “tie” with a threshold of 5 mmHg. Then, ties from the ASBP comparison underwent the comparison using OSBP with a threshold of 10 mmHg. Any tie for a pair comparing OSBP resulted in comparison of number of anti-hypertensive medications with a threshold of 1. Comparisons of ASBP and OSBP were adjusted for baseline SBPs by using residuals from a linear regression. The analysis was repeated for patients grouped according to history of obstructive sleep apnea (OSA) at baseline. Results In March 2020, 336 patients with AF at baseline and 2,394 patients with no AF were compared in GSR, resulting in 336 x 2394 = 804,384 pairwise comparisons for the win ratio analysis. A total of 285,709 “wins”, indicating greater ASBP reduction, OSBP reduction, and/or fewer number of anti-hypertensive medications occurred in the AF group compared to the no AF group. Conversely, 256,511 “losses”, meaning greater BP reduction and/or number of medications occurred in the no AF group. The win ratio was thus calculated as 1.11 (95% CI: 0.98, 1.28, p=0.081) indicating similar BP reduction and medication burden after RDN in patients with or without AF in GSR (Figure). Using these methods, the win ratio for patients with and without OSA was calculated to be 0.98 (95% CI: 0.85, 1.13, p=0.81), also indicating similar RDN efficacy regardless of presence of OSA at baseline (Figure). Previously published results of the win ratio analysis of RDN and sham control patients in the SPRYAL HTN-ON MED trial reported a win ratio in favor of RDN of 2.78 (95% CI: 1.58, 5.48, p&amp;lt;0.001). Conclusions Application of the win ratio methodology to patients in GSR demonstrated similar efficacy of RDN to patients regardless of whether they had comorbidities of atrial fibrillation or obstructive sleep apnea. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Medtronic

Renal denervation in patients with versus without chronic kidney disease: results from the Global SYMPLICITY Registry with follow-up data of 3 years.

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. 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. 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. 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.

PATIENTS WITH RESISTANT HYPERTENSION AND ATRIAL FIBRILLATION ARE THE BEST RESPONDERS FOR RENAL DENERVATION

Objective: The search for the ideal candidate for renal denervation (RDN) is one of the priority treatments of patients with resistant hypertention (RH). Our objective was to identify the predictors of the efficiency of renal denervation. Design and method: The study included 112 patients with RH. The average age of patients was 53 [19; 69] years. Twenty-four (21.4%) patients had atrial fibrillation (AF). Four (16.7%) patients had chronic AF, 8 (33.3%) patients had persistent AF, and 12 (50%) – paroxysmal AF. All patients underwent RDN. Procedure was performed by an experienced electrophysiologist at the renal arteries using specialized electrode Symplicity Flex (Medtronic): ablation power = 8 - 10 W at 55°C, 4 – 10 points for each renal artery (including brunches), 2 minutes per point. Office BP and 24-hour ambulatory BP, 24-hour ECG monitoring, arrhythmia chronocard diaries were measured before, at 6 and 12 months of follow-up. A logistic regression analysis included the following parameters: gender, age, body mass index, office and 24-hour ambulatory systolic blood pressure (SBP), diabetes mellitus and the AF presence. Results: baseline office SBP and DBP in patients with RH were 185.4 ± 29.19 and 109.96 ± 17.95 respectively. Office BP decreased by 29.8 /14.1 mmHg at 12 month after RDN (p &lt; 0.001). 24-hour ambulatory SBP decreased from 161.3 ± 25.9 mm Hg to 148.1 ± 21.3 mm Hg at 12 months after the intervention, DBP from 94.3 ± 16.4 mm Hg to 87.2 ± 15.9 mmHg (p &lt; 0,001). It was found that all patients (100%) with RH and AF were responders to renal denervation. This response is defined as a reduction of office SBP of less than 10 mmHg following RDN. Whereas 17.2% of non-AF group patients were non-responders. The number of symptomatic AF paroxysms significantly decreased from 9 [2; 11] to 2 [1; 3] one year after RDN (p = 0.001). Conclusions: Patients with RH and AF are among the best candidates for RDN. It may help to improve the selection of patients with arterial hypertension for the RDN.

Extended-Release Carvedilol in the Treatment of Hypertension: A Double-Blind, Randomized, Placebo-Controlled Trial.

Immediate-release carvedilol requires twice-daily dosing and may have low treatment compliance. We assessed the efficacy of a new formulation of once-daily extended-release carvedilol (carvedilol ER) on systolic blood pressure (SBP) and diastolic blood pressure (DBP) among patients with hypertension in this double-blind, randomized, placebo-controlled trial. A total of 134 patients with untreated or uncontrolled hypertension were randomly assigned in a 1:1:1 ratio to receive placebo, low-dose carvedilol ER, or high-dose carvedilol ER for 8 weeks. The primary endpoint was the reduction in office SBP at 8 weeks. Secondary endpoints included the reduction in office DBP and the proportion of patients with blood pressure (BP) < 140/90 mm Hg. In the intention-to-treat population, placebo-adjusted changes in SBP/DBP were -2.9 mm Hg [95% confidence interval (CI), -9.6 to 3.7]/-1.7 mm Hg (95% CI, -5.6 to 2.3) and -4.9 mm Hg (95% CI, -11.5 to 1.7)/-3.4 mm Hg (95% CI, -7.3 to 0.5) for low-dose carvedilol ER and high-dose carvedilol ER, respectively. In the per-protocol population, high-dose carvedilol ER was associated with a significant DBP reduction [placebo-adjusted difference, -4.7 mm Hg (95% CI, -8.8 to -0.5); adjusted p = 0.026]. There was a gradational improvement in BP control with carvedilol ER (25%, 37%, and 48% for placebo, low-dose carvedilol ER, and high-dose carvedilol ER, respectively; linear-by-linear association p = 0.028). There were no differences in safety among the three groups. Carvedilol ER, though well tolerated, did not result in a greater reduction in either SBP or DBP compared with placebo.

An Open-label, Single-arm, Multicenter Feasibility Study Evaluating the Safety of Catheter-based Renal Denervation with DENEX™ in Patients with Uncontrolled Hypertension on Standard Medical Therapy.

Background and ObjectivesDENEX™ is a novel renal sympathetic denervation (RDN) system that is equipped with 3 electrodes that deliver radiofrequency energy to the renal nerves along renal arteries. The purpose of this study was to evaluate the safety and efficacy of RDN with DENEX™ in resistant hypertension.MethodsThis was an open-label, single-arm, multicenter, first-in-man pilot study. Between November 2016 and May 2018, a total of 16 patients were enrolled at 4 centers in South Korea. The inclusion criteria were systolic blood pressure (SBP) ≥150 mmHg and use of 3 or more antihypertensive medications, including diuretics. The primary objective was the safety outcome of RDN with the DENEX™ system. The secondary objective was efficacy outcome based on changes of office, and 24-hour ambulatory SBP from baseline to 3 months. The patients underwent abdominal computed tomography (CT) or duplex ultrasonogram before and 6 months after RDN.ResultsNo major adverse events occurred after RDN for 6 month of follow-up period. There was no vascular complication either by CT or duplex ultrasonogram. The office SBP was significantly reduced from 164.6±11.6 mmHg at baseline to 142.0±20.4 mmHg (−24.4±24.4 mmHg, p=0.003) at 3 months. The ambulatory SBP was reduced from 151.44±12.85 mmHg at baseline to 140.0±16.5 mmHg (−13.1±18.9 mmHg, p=0.056) at 3 months.ConclusionRDN with the DENEX™ system showed a favorable safety profile in resistant hypertension. A significant reduction in office SBP and a borderline reduction in ambulatory SBP were observed.Trial RegistrationClinicalTrials.gov Identifier: NCT04248530

EFFECTS OF RENAL DENERVATION IN PATIENTS WITH VERSUS WITHOUT CHRONIC KIDNEY DISEASE

Objective: Activity of the sympathetic nervous system (SNS) is increased in hypertensive patients with chronic kidney disease (CKD). In this updated version, we tested the hypothesis whether hypertensive patients with CKD enrolled in the Global Symplicity Registry (GSR) showed different responses in blood pressure (BP) reduction in the short- and long-term follow-up. Design and method: The GSR (NCT 01534299) is a prospective, open-label, international, multicentre observational study for assessment of safety and effectiveness of renal denervation (RDN) among real-world patients treated with the Symplicity™ RDN system (Medtronic, Santa Rosa, CA, USA). Inclusion criteria are age >= 18 years and eligibility for RDN. Office and 24-h ambulatory BP were assessed at pre-specified time-points (12, 24 and 36 months). For the current updated analyses, enrolled patients (N = 1980) were stratified based on baseline estimated glomerular filtration rate in <60 vs. >= 60 ml/min/1.73m2 into with (N = 475) and without (N = 1505) CKD groups. Results: Patients with CKD were significantly older (p < 0.0001) and more likely to be female (p = 0.0027) compared to patients without CKD. At baseline office systolic BP was lower (162.4 ± 26 vs. 165.8 ± 24 mmHg, p = 0.0113), whereas there was no difference in baseline 24-h ambulatory systolic BP (153.6 ± 19 vs. 153.7 ± 18 mmHg, p = 0.9162), in patients with, compared to without CKD. In patients with and without CKD, office as well as 24-h ambulatory BP were significantly reduced after RDN compared to baseline values at all time-points (all p < 0.001). There was a greater office systolic BP reduction in favor of patients without compared to with CKD, whereas no difference in 24-h ambulatory systolic BP reduction after RDN, even after adjustment (Table), was observed.Conclusions: After adjustment for baseline data, BP reduction after RDN showed a disparate response pattern in office and 24-h ambulatory BP reductions in patients with CKD. Data needs to be confirmed by a rigorously conducted, prospective, double-blind, sham-controlled study.