Similar Reductions In Blood Pressure Research Articles

Atrioventricular Interval Modulation (AVIM) therapy for ambulatory systolic blood pressure (aSBP) reduction with a dual chamber pacemaker: comparison of conduction system vs. right ventricular pacing

Abstract Background AVIM is a pacing algorithm incorporated into dual-chamber pacemakers to treat hypertension. AVIM delivers repeating sequences of short and longer atrioventricular delays leading to reduced preload and afterload. The therapy lowers blood pressure while simultaneously modulating the autonomic nervous system. The marked blood pressure reducing capability of AVIM has been already confirmed by a previous randomized clinical trial using conventional right ventricular (RV) pacing. Nevertheless, whether a similar blood pressure reduction could be also achieved by AVIM when conduction system pacing (CSP) is applied instead of RV pacing has not been investigated yet. Considering the facts that CSP using Left Bundle Branch Area Pacing (LBBAP) has been found to elicit more synchronous ventricular contraction and improved hemodynamics compared to RV pacing and AVIM is associated with a signficant burden of ventricular pacing, it is tempting to hypothesize that AVIM with CSP could be particularly beneficial. Purpose To compare the effects of AVIM therapy when delivered via an LBBAP location with the effects when delivered using a traditional RV lead location. Methods This single-center study evaluated subjects indicated for a dual chamber pacemaker who also had uncontrolled hypertension despite a stable dose of ³ 1 antihypertensive drug. Leads were placed in the RV or the LBBAP position. Subjects entered a run-in period of 4 weeks in which baseline office (oSBP)and 24-hour aSBP were measured. Subjects with baseline aSBP >130 mmHg and oSBP>140 mmHg at week 4 were included in the study. AVIM therapy was activated and a 24-hour aSBP was performed immediately after activation. Results Using a dedicated CSP pacemaker lab setup, CSP was performed in 5 patients with the Select Secure electrode (model 3830-69 cm) delivered via a fixed curve sheath (C315HIS). During the run in phase, in 3 out of the 5 CSP-AVIM patients, high blood pressure did not reach the level of inclusion and therefore these patients were not used for further analysis. In the remaining two patients, AVIM was activated. These two patients had a V6 stimulus-peak time of 69 ms and 61 ms, while V1 stimulus peak time was: 121ms and 109ms respectively. The effect of AVIM on 24-hour aSBP in the activated CSP-AVIM patients was compared to the average effect seen in patients from the same center enrolled in the prior randomized study with leads in the RV. Table 1 shows individual aSBP values for the two patient groups. Results suggest that delivery of AVIM therapy through leads in either position generates a significant reduction in blood pressure: -24.1 mmHg vs. -15.4 mmHg when the lead is placed in LBBAP or RV positions respectively. Conclusion These results demonstrate a significant reduction in aSBP in both lead locations. Additional studies evaluating larger sample sizes are required to assess if specific lead positions are preferable.Table 1

TEN YEAR FOLLOW-UP OF PATIENTS WITH RESISTANT HYPERTENSION RANDOMIZED TO RENAL DENERVATION OR ANTIHYPERTENSIVE DRUG TREATMENT

Objective: Renal denervation (RDN) is a treatment option in resistant hypertension. The procedure is considered safe, although randomized trials only demonstrate a moderate blood pressure (BP) lowering effect, when considering medication adherence. Some observational studies describe reduction in BP several years after the procedure. The aim of the study was to describe long-term safety and potential benefits of RDN after ten years, compared to optimized drug treatment, measuring serum concentration of antihypertensive drugs to ensure adherence. Design and method: We report data from ten year follow-up of patients randomized to RDN (n=9) or drug adjustment (n=10). Initially the patients had treatment-resistant hypertension, defined as daytime systolic ambulatory BP >= 135 mmHg after witnessed intake (directly observed therapy, DOT) of >= 3 antihypertensive drugs including a diuretic and therefore considered as adherent. One year after RDN or drug adjustment, we optimized antihypertensive medication for all patients. Thereafter, patients received appropriate antihypertensive treatment in primary or secondary care, according to their BPs. Patients were informed of serum concentration measurements performed at the 7-year visit. At the 10-year visit, serum drug measurements before DOT and ambulatory BP measurement (ABPM) were used for evaluation of adherence. Antihypertensive agents were registered, glomerular filtration rate (eGFR) was estimated by the CKD-EPI formula using creatinine and Cystatin C, and renal arteries were examined by CT or MRI. Results: All living patients (n=18) attended the 10-year visit, now mean age 69 years, using 4±2 antihypertensive agents, with no difference between groups. Serum concentrations confirmed that all patients were adherent to reported medication. There were significant and similar BP reductions in both groups compared to baseline; daytime ABPM -22±15/9±8 mmHg in the RDN group, and -20±15/13±7 mmHg in the control group (figure). No patients developed renal artery stenosis. The decrease in eGFR was similar in both groups. Conclusions: To our knowledge this is the RCT with the longest follow-up supporting long-term safety of RDN in patients with resistant hypertension. Daytime ABPM improved during 10 years of follow-up, not explained by RDN, but due to adjustments in antihypertensive regimens and probably better adherence to medication.

Adrenoceptors and Hypertension.

Hypertension is a very prevalent condition associated with high mortality and morbidity, secondary to changes resulting in blood vessels and resultant end-organ damage. Haemodynamic changes, including an initial rise in cardiac output followed by an increase in total peripheral resistance, denote the early changes associated with borderline or stage 1 hypertension, especially in young men. Increased sodium reabsorption leading to kidney damage is another mechanism proposed as one of the initial triggers for essential hypertension. The underlying pathophysiological mechanisms include catecholamine-induced α1- and ß1-adrenoceptor stimulation, and renin-angiotensin-aldosterone system activation leading to endothelial dysfunction which is believed to lead to persistent blood pressure elevation.α1 blockers, α2 agonists, and ß blockers were among the first oral anti-hypertensives. They are no longer first-line therapy after outcome trials did not demonstrate any benefits over and above other agents, despite similar blood pressure reductions. Angiotensin-converting enzyme inhibitors(or angiotensin receptor blockers), calcium channel blockers, and thiazide-like diuretics are now considered the first line of therapy, although adrenoceptor agents still have a role as second- or third-line therapy. The chapter also highlights hypertension in specific medical conditions such as pregnancy, phaeochromocytoma, hyperthyroidism, portal hypertension, pulmonary arterial hypertension, and ocular hypertension, to provide an overview for clinicians and researchers interested in the role of adrenoceptors in the pathophysiology and management of hypertension.

Obese Male Mice Exposed to Early Life Stress Display Sympathetic Activation and Hypertension Independent of Circulating Angiotensin II.

We have previously reported that male mice exposed to maternal separation and early weaning (MSEW), a model of early life stress, show sympathetic activation and increased blood pressure in response to a chronic high-fat diet. The goal of this study was to investigate the contribution of the renin-angiotensin-aldosterone system to the mechanism by which MSEW increases blood pressure and vasomotor sympathetic tone in obese male mice. Mice were exposed to MSEW during postnatal life. Undisturbed litters served as controls. At weaning, both control and MSEW offspring were placed on a low-fat diet or a high-fat diet for 20 weeks. Angiotensin peptides in serum were similar in control and MSEW mice regardless of the diet. However, a high-fat diet induced a similar increase in angiotensinogen levels in serum, renal cortex, liver, and fat in both control and MSEW mice. No evidence of renin-angiotensin system activation was found in adipose tissue and renal cortex. After chronictreatment with enalapril (2.5 mg/kg per day, drinking water, 7 days), an angiotensin-converting enzyme inhibitor that does not cross the blood-brain barrier, induced a similar reduction in blood pressure in both groups, while the vasomotor sympathetic tone remained increased in obese MSEW mice. In addition, acute boluses of angiotensin II (1, 10, 50 μg/kg s.c.) exerted a similar pressor response in MSEW and control mice before and after enalapril treatment. Overall, elevated blood pressure and vasomotor sympathetic tone remained exacerbated in MSEW mice compared with controls after the peripheral inhibition of angiotensin-converting enzyme, suggesting a mechanism independent of angiotensin II.

Blood pressure reduction after renal denervation in patients with or without chronic kidney disease.

Renal denervation (RDN) has emerged as an adjacent option for the treatment of hypertension. This analysis of the Erlanger registry aimed to compare the blood pressure (BP)-lowering effects and safety of RDN in patients with and without chronic kidney disease (CKD). In this single-center retrospective analysis, 47 patients with and 127 without CKD underwent radiofrequency-, ultrasound- or alcohol-infusion-based RDN. Office and 24-h ambulatory BP and estimated glomerular filtration rate (eGFR) were measured at baseline, and after 6 and 12months. A total of 174 patients with a mean age of 59.0±10years were followed up for 12months. At baseline, mean eGFR was 55.8±21mL/min/1.73 m2 in patients with CKD and 87.3±13mL/min/1.73 m2 in patients without CKD. There was no significant eGFR decline in either of the groups during 12months of follow-up. In patients without CKD, office systolic and diastolic BP were reduced by -15.3±17.5/-7.9±10.8mmHg 6months after RDN and by -16.1±18.2/-7.7±9.6mmHg 12months after RDN. In patients with CKD, office systolic and diastolic BP were reduced by -10.7±24.0/-5.8±13.2mmHg 6months after RDN and by -15.1±24.9/-5.9±12.9mmHg 12months after RDN. Accordingly, in patients without CKD, 24-h ambulatory systolic and diastolic BP were reduced by -7.2±15.8/-4.9±8.8mmHg 6months after RDN and by -9.0±17.0/-6.2±9.8mmHg 12months after RDN. In patients with CKD, 24-h systolic and diastolic BP were reduced by -7.4±12.9/-4.2±9.9mmHg 6months after RDN and by -8.0±14.0/-3.6±9.6mmHg 12months after RDN. There was no difference in the reduction of office and 24-h ambulatory BP between the two groups at any time point (all P>.2). Similar results have been found for the 6months data. With exception of rare local adverse events, we did not observe any safety signals. According to our single-center experience, we observed a similar reduction in 24-h, day and night-time ambulatory BP as well as in-office BP in patients with and without CKD at any time point up to 12months. We conclude that RDN is an effective and safe treatment option for patients with hypertension and CKD.

Abstract 13852: Sex Differences in Blood Pressure Reduction and Cardiovascular Outcomes in Patients With Resistant Hypertension Undergoing Radiofrequency Renal Denervation: Global SYMPLICITY Registry DEFINE

Introduction: Hypertension (HTN) prevalence and outcomes differ by sex. Radiofrequency renal denervation (RF RDN) safely reduces blood pressure (BP) in patients with resistant HTN. Hypothesis: After RF RDN, there are no sex-based differences in BP changes and cardiovascular (CV) outcomes. Methods: The Global SYMPLICITY Registry (GSR) DEFINE is an all-comer registry of patients with uncontrolled BP undergoing RF RDN. BP changes (analysis of covariance [ANCOVA] adjusted for baseline BP and age), CV death, stroke, myocardial infarction (MI) rates at 3yrs were compared between sexes with office systolic BP (OSBP) ≥140mmHg, prescribed ≥3 anti-HTN drugs. Results: Patients enrolled up to March 2023 were included (N=2502, female=1062). Females were older (62 vs 59 y; p<0.0001), less likely to have a history of sleep apnea (12.5 vs 25.0% p<0.0001), cardiac disease (45.2 vs 50.3%; p<0.0012) and smoking (19.1 vs 41.3%; p<0.0001). Body mass index, rates of diabetes and chronic kidney disease, number of anti-HTN drugs (5.1±1.5 in both sexes; p=0.88) and 24-hr SBP were similar by sex. Baseline OSBP was higher in females (174±23 vs 169±19mmHg; p<0.0001). After 3yrs, OSBP significantly decreased in both sexes from baseline (female: -21.5mmHg vs male: -20.4mmHg; ANCOVA adjusted difference: 3.2mmHg [95% CI: 0.5 to 6.0; p=0.021]). There was no difference in 24-hr SBP change (Figure 1A) or number of anti-HTN drugs by sex. CV death rate was significantly higher in females (4.1% vs 2.1% vs p=0.024), but MI rate was significantly lower in females (1.3% vs 3.5%; p=0.007). Stroke rate was similar by sex (Figure 1). Conclusion: Females with resistant hypertension referred for RF RDN were older, had higher OSBP with fewer comorbidities compared to males. Despite similar BP reductions up to 3yrs after RF RDN, CV death rate in females was greater than males. These results suggest the need for sex specific analyses and control of HTN in females.

A Review of the Safety and Efficacy of Bexagliflozin for the Management of Type 2 Diabetes.

To review the pharmacology of bexagliflozin in addition to its safety and efficacy from available clinical trials used for its approval, as well as available clinical evidence to date. A search of the National Institutes of Health Clinical Trials Registry (http://www.clinicaltrials.gov) and PubMed database was performed from inception through June 1, 2023. The following study designs were included: meta-analyses, systematic review, clinical trial, or observational study design. Abstracts and drug monographs were also reviewed. Narrative or scoping reviews were excluded. Only articles in the English language and those evaluating the pharmacology, pharmacokinetics, safety, or efficacy of bexaglifozin in humans were included. Bexagliflozin reduces hemoglobin A1c ~0.5% with similar reductions in systolic blood pressure and body weight to other SGLT2 inhibitors. No cardiovascular outcomes trial is published, nor ongoing at this time. Adverse effects are similar to other SGLT2 inhibitors (genital mycotic and urinary tract infections, increased urination) including a warning for lower extremity amputation similar to canagliflozin. Although no cost-effectiveness data are available, statements from the manufacturer suggest a competitive price point. Given limited trial data, lower cost, if chosen, may create a temporary niche for bexagliflozin pending generic availability of other SGLT2 inhibitors. However, given lack of cardiovascular and renal outcome data, empagliflozin, dapagliflozin, or canagliflozin may be preferred. Bexagliflozin appears safe and effective as monotherapy and add-on pharmacological therapy for the treatment of T2D.

BLOOD PRESSURE REDUCTION AFTER RENAL DENERVATION IN PATIENTS WITH OR WITHOUT CHRONIC KIDNEY DISEASE: THE ERLANGER EXPERIENCE

Objective: Renal denervation (RDN) has emerged as an adjacent option for the treatment of hypertension. This analysis of the ERLANGER registry aimed of comparing the blood pressure (BP) lowering effects and safety of RDN in patients with and without CKD. Design and method: Radiofrequency, ultrasound or alcohol-infusion device based RDN was performed in 47 patients with and 127 without CKD. Office and 24-h ambulatory BP were measured at baseline, after 6 and 12 months. We splitted the study cohort based on the median systolic 24h ABP reduction after 6 months into responders and non-responders and compared baseline characteristics between these groups. CKD was defined by clinical diagnosis, estimated glomerular filtration rate (eGFR: 15-59 ml/min/1.73m2) or A2 albuminuria (> = 30 mg/g creatinine ). Results: 174 patients with a mean age of 59.0±10 were followed up for at least 12 months. At baseline mean eGFR was 55.8±21 ml/min/1.73m2 in patients with CKD and 87.3±13 ml/min/1.73m2 in patients without CKD according to the CKD-EPI formula. There was no significant eGFR decline in either of the groups during follow up. Office and 24-h systolic and diastolic BP were significantly reduced from baseline in patients with or without CKD at all time points after RDN (all p<0.01). There was no significant difference in the reduction of 24h, day- and nighttime ABP between the 2 groups at any time point (see table below). In addition to 24h baseline systolic ABP we identified several predictors (all p < 0.05): patients with a high baseline office heart rate (HR), without T2D, without diuretic medication and current smokers were more likely to be responders. With exception of rare local adverse events (e.g. haematoma at the puncture site), we had no safety signals, especially in our patients with CKD. Conclusions: According to our single center experience, we observed a similar reduction in 24-h, day and nighttime ambulatory BP as well as in office BP in patients with and without CKD at any time point up to 12 months. We conclude that RDN is an effective and safe treatment option for patients with arterial hypertension and CKD.

Using Renin Activity to Guide Mineralocorticoid Receptor Antagonist Therapy in Patients with Low Renin and Hypertension.

Mineralocorticoid receptor antagonists (MRAs) are often empirically used for patients with low-renin hypertension (LRH) or probable primary aldosteronism (PA) who decline surgery. However, the optimal approach to MRA therapy is unknown. Studies have shown that a rise in renin is an effective biomarker of prevention of cardiovascular complications of PA. This study aimed to determine whether empiric MRA therapy in patients with LRH or probable PA targeting unsuppressed renin is associated with a decrease in blood pressure and/or proteinuria. Retrospective single-center cohort study from 2005 to 2021 included adults with LRH or probable PA (renin activity <1.0 ng/ml/h and detectable aldosterone levels). All patients were empirically treated with an MRA, targeting renin ≥1.0 ng/ml/h. Out of 39 patients studied, 32 (82.1%) achieved unsuppressed renin. Systolic and diastolic blood pressure decreased from 148.0 and 81.2 to 125.8 and 71.6 mm Hg, respectively (P < 0.001 for both). Similar blood pressure reductions were seen whether patients had high (>10 ng/dl) or low (<10 ng/dl) aldosterone levels. The majority (24/39; 61.5%) of patients had at least one baseline anti-hypertensive medication stopped. Among the six patients who had detectable proteinuria and albumin-to-creatinine (ACR) measurements post-treatment, the mean ACR decreased from 179.0 to 36.1 mg/g (P = 0.03). None of the patients studied had to completely stop treatment due to adverse reactions. Empiric MRA therapy in patients with LRH or probable PA targeting unsuppressed renin can safely and effectively improve blood pressure control and reduce proteinuria.

Prospective evaluation of digital therapeutic intervention on blood pressure control in Indian patients with uncontrolled primary hypertension

Abstract Funding Acknowledgements Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Terrals Technologies Private Limited Background Digital therapeutics (DTx) has emerged as a new approach in recent years making use of connected devices, smartphone software and electronic communication tools to help manage chronic cardiovascular diseases such as hypertension. Considering its nascent stage, many questions still remain with respect to its applicability, effectiveness and limitations. Purpose Assess the effectiveness of digital therapeutic intervention in controlling blood pressure in Indian patients with primary hypertension Methods We conducted a prospective, 12 week, single arm, interventional study, including 125 subjects at multiple sites in India. Subjects with uncontrolled primary hypertension (≥140 mmHg systolic and/or ≥90 mmHg diastolic) in the age group of 30-65 years who were under routine antihypertensive treatment were enrolled. They were provided supplementary DTx intervention comprising of smartphone application based personalized management of diet, exercise, self monitoring and health education by nutritionists and health coaches. Efficacy endpoints such as blood pressure (BP), body mass index (BMI), lipids, etc. were measured before and after the intervention. Results A total of 122 subjects who completed the trial had mean age of 47.44 ± 9.43 years, comprising 58 (48%) male and 64 (52%) female patients and mean BMI of 27.21 ±4.7 kg/m². Post-intervention change in mean systolic BP (SBP) was -25.61 mmHg (95% CI 22.55 - 28.66, 154.98 mmHg vs 129.37 mmHg, P&amp;lt;.001). The post-intervention change in mean diastolic BP (DBP) was -18.62 mmHg (95% CI 16.29 - 20.96, 100.04 mmHg vs 81.42 mmHg, P&amp;lt;.001). Patients with stage 1 hypertension (69.6%) achieved mean systolic reduction of 20.87 ± 13.9 mmHg, (148.54 mmHg vs 127.67 mmHg, P&amp;lt;.001). The patients with stage 2 (27.04%) and stage 3 (3.27%) hypertension achieved a higher mean SBP reduction of 34.67 ± 15.19 mmHg (167.24 mmHg vs 132.58 mmHg, P&amp;lt;.001) and 51.5 ± 40.45 mmHg (190.75 mmHg vs 139.25 mmHg, P=.084), respectively. Male and female patients showed almost similar reduction in systolic BP of 25.47 ± 14.72 and 25.73 ± 19.39 mmHg, respectively. Also, the subjects with other chronic comorbidities (23.9%) achieved a mean systolic BP reduction of 29.51 ± 15.25 mmHg. A total of 79.51% (n=97) patients achieved the SBP &amp;lt;140 mmHg, while 59.84% (n=73) patients achieved SBP &amp;lt;130 mmHg. Combining both the systolic and diastolic targets together, 65.57% (n=80) patients achieved the target of &amp;lt;140/90 mmHg, while ESC/ESH 2018 recommended BP target of &amp;lt;130/80 mmHg was achieved by 31.15% (n=38) patients. Conclusion The implementation of Digital therapeutic application integrated with primary healthcare resulted in significant reduction in blood pressure in participants with uncontrolled hypertension. Greater improvement was observed in participants with higher baseline blood pressure.

PS-P06-8: TEXT MESSAGING AND HOME BLOOD PRESSURE MONITORING FOR PATIENTS WITH UNCONTROLLED HYPERTENSION: A PILOT RANDOMIZED CONTROLLED TRIAL

Objective: Improving adherence to antihypertensive medications is the most significant modifiable patient related factor to achieving blood pressure (BP) control. Elevated BP remains the leading cause of death globally. BP trends show disparities in the burden of hypertension in black and low socioeconomic status (LSES) populations, accompanied by low levels of awareness, treatment and control rates. Telehealth systems using text messaging (SMS) and home blood pressure monitors (HBPM) represent attractive scalable tools to reduce BP in those with health disparities. Design and methods: In three ambulatory clinics that serve a large number of those with LSES affiliated with an academic institution, we conducted a randomized controlled pilot study for low medication adherent patients with poorly controlled hypertension (BP &gt; 130/80). The pilot aimed to (1) evaluate the feasibility of recruiting LSES participants to an effectiveness trial of SMS plus HBPM vs HBPM only; (2) measure the acceptability of the SMS system and (3) estimate the effects of the SMS approach on lowering BP. Satisfaction was measured using the validated systems usability survey (SUS). The SMS system was designed with the input of LSES focus groups and used Twilio® as its bidirectional platform. From February 2021 to October 2021, 24 participants were randomized (1:1) to either SMS intervention plus HBPM with an Omron BP cuff or HBPM alone for 12 weeks. Results: During the study period, the study coordinator enrolled 24 participants, averaging 3 per month. Demographics: participants were male (N = 14/24), predominantly African American (AA); (n = 19/24); 13/24 had high school education or less; mean age 55.7 (SD 12); weight 97.4 kg (SD 14); Mean initial SBP 156 mmHg (SD 20), DPB 100 mmHg (SD 11). Acceptability: 8/12 participants responded via SMS with at least one BP measurement in the SMS arm. Two participants were lost to follow up in each arm. Mean SUS was 81.6 (scale of 0 to 100, &gt; 68 is considered above average). Reduction in SBP at 12 weeks in the SMS group and control group was 15 mmHg and 13 mmHg respectively (p = 0.58). Conclusion: Recruiting and retaining LSES participants with uncontrolled HTN for a larger trial of telehealth with SMS and HBPM is feasible and well accepted. Similar BP reductions were achieved in both arms. Utilizing the SMS and HBPM shows promise in reducing BP in the LSES population. A larger efficacy trial is needed to determine best practice and reduce cardiovascular health disparities.

JS-HR-10: ADVANCES IN RENAL DENERVATION FOR TREATING HYPERTENSION

Excessive activation of sympathetic nervous system is closely related to the onset and progression of hypertension. Renal nerves are composed of sympathetic efferent and sensory afferent nerves. Activation of the efferent renal sympathetic nerves induces renin secretion, sodium absorption, and increased renal vascular resistance, which lead to increased blood pressure (BP) and fluid retention. Afferent renal sensory nerves, which are densely innervated in the renal pelvic wall, project to the cardiovascular center in the brain to modulate sympathetic outflow to the periphery, including the heart, kidneys, and arterioles. Renal denervation (RDN) is a neuromodulation therapy that partially interrupts both the efferent outputs from the brain to the kidney and the afferent inputs from the kidney to the brain and has attracted attention as a novel device therapy for hypertension. In clinical practice, denervation is performed through the lumen of the renal artery using a catheter. Radiofrequency, ultrasound, and alcohol-based RDN devices are being developed as new second-generation devices. A randomized sham-controlled trials using 24-hour ambulatory BP measurement is required for approval of clinical use of RDN. The SPYRAL HTN OFF-MED pivotal trial showed the superiority of RDN using radiofrequency-based catheter compared with a sham procedure to safely lower 24-hour systolic BP in the absence of antihypertensive medications. The RADIANCE-HTN TRIO trials showed the superiority of RDN using ultrasound-based catheter compared with a sham procedure to safely lower daytime BP in patients with resistant hypertension. The REQUIRE trial is the first trial of ultrasound RDN in Asian patients from Japan and South Korea with resistant hypertension. The study findings were neutral for the primary endpoint, with similar reductions in 24-hour systolic BP in the RDN and sham control groups. Although BP reduction after RDN was similar to other sham-controlled studies, the sham group in this study showed much greater reduction. Japanese Society of Hypertension performed the meta-analysis of nine randomized sham-controlled trials of RDN including these three trials mentioned above. The results showed that RDN significantly reduced a range of office, home and 24-hour BP parameters in patients with resistant, uncontrolled, and drug-naïve hypertension. There were no significant differences in magnitude of BP reduction between radiofrequency-based and ultrasound-based devices. Recently, the efficacy and safety of RDN in the SPYRAL HTN OFF-MED pivotal trial up to 36 months have been reported. In this session, the latest basic and clinical evidence/aspects of RDN will be summarized and discussed, which is about to be introduced into the clinical practice.

PS-BPC12-2: EFFICACY AND SAFETY OF SINGLE-PILL COMBINATION OF OLOMAX&amp;ACIRC; (OLMESARTAN, AMLODIPINE, AND ROSUVASTATIN) IN HYPERTENSIVE PATIENTS WITH LOW-TO-MODERATE CARDIOVASCULAR RISK

Objective: Of the ten hypertensive patients who have to take statins in Korea, about two are not actually prescribed. The use of polypills including lipid-lowering and blood pressure (BP)-lowering drug improves medication adherence, and consequently ameliorates in cardiovascular risk levels. This study was to evaluate the efficacy and safety of single-pill triple-combination of olmesartan/amlodipine/rosuvastatin (OLOMAX®) in comparison to single-pill dual-combination of olmesartan/amlodipine (SEVIKAR®) in hypertensive patients with low-to-moderate cardiovascular risk. Design and method: This multicenter, active-control, randomized study included 106 hypertensive patients with low-to-intermediate cardiovascular risk, who were randomly assigned to receive either OLOMAX®(20/5/5 mg, treatment 1), OLOMAX®(20/5/10 mg, treatment 2), or SEVIKAR®(20/5 mg, control) once daily for 8 weeks. The low and moderate cardiovascular risk groups were defined according to the definition of the 4th Korean dyslipidemia treatment guidelines. Primary endpoint was assessed as the difference of the percent change of LDL-C(low-density lipoprotein-cholesterol) level at 8 weeks from baseline among the three groups. Results: The difference in the least square mean % change of LDL-C in the treatment 1 and 2 groups compared to the control group at 8 weeks was -32.6 ± 3.7% and -45.9 ± 3.3%, respectively (all p &lt; 0.001). There was significant difference in the achievement rate of LDL-C levels &lt; 100 mg/dL at 8 weeks between the three groups (65.8% for the treatment 1 group, 86.7% for the treatment 2 group, and 6.25% for the control group, p &lt; 0.001). The results of total cholesterol, triglycerides, high-density lipoprotein-cholesterol, apolipoprotein B, and apolipoprotein B/apolipoprotein A1 showed the superiority in the treatment 1 and 2 groups compared to the control group. Meanwhile, there was no significant difference in systolic and diastolic BPs and diabetes-related variables including fasting glucose, fructosamine, and hemoglobinA1c at 8 weeks between the three groups. Adverse drug reaction (ADR) developed only 1 case (constipation) in the treatment 1 group and serious ADR did not occur in the three groups. Medication adherence rates were highly excellent in the three groups (98.0% for the treatment 1 group, 99.7% for the treatment 2 group, and 96.3% for the control group, p &gt; 0.05). Conclusions: Single-pill triple-combination of olmesartan/amlodipine/rosuvastatin were superior to single-pill dual-combination of olmesartan/amlodipine in LDL-C lowering effect, with similar BP reduction effects and excellent safety profiles in hypertensive patients with low to moderate cardiovascular risk.

PS-C36-8: BLOOD PRESSURE REDUCTION AFTER RENAL DENERVATION IN PATIENTS WITH OR WITHOUT CHRONIC KIDNEY DISEASE: THE ERLANGER EXPERIENCE

Background: Hypertension is associated with major cardiovascular and renal adverse events and the 24h-ambulatory blood pressure (BP) is superior than the office BP in predicting these complications. Overactivitiy of the sympathetic nervous system is linked with elevation of systemic BP and is also present in patients with chronic kidney disease (CKD). The aim of this study was to compare the BP lowering effects of renal denervation (RDN) in patients with and without CKD. Methods: Radiofrequency or ultrasound device based renal denervation was performed in 47 patients with and 127 without CKD in our center. Office and 24h-ambulatory BP were assessed after 3, 6 and 12 months by validated devices. CKD was defined by clinical diagnosis or according to the estimated glomerular filtration rate (eGFR: 15–60 ml/min/1.73m2; CKD-EPI formula). Results: Until today, 174 patients with a mean age of 59.0 ± 10 were followed up for at least 12 months. At baseline mean eGFR was 55.8 ± 21 ml/min/1.73m2 in patients with CKD and 87.3 ± 13 ml/min/1.73m2 in patients without CKD. There was no significant eGFR decline in either of the groups during follow up. In patients with CKD eGFR was after 12 months 54.4 ± 23 ml/min/1.73m2 (p = 0.699 vs baseline). Office and 24h-systolic and -diastolic BP were significantly reduced from baseline in patients with or without CKD at all time points after RDN (all p &lt; 0.01). There was no significant difference in the reduction of 24 h, day- and nighttime ambulatory BP between the 2 groups at any time point (see table below). With exception of rare local adverse events (e.g. haematoma at the puncture site), we had no safety signals, especially in our patients with CKD, e.g. there was no dissection, embolism or periprocedural cardiovascular complications. Conclusion: In our single center registry, we observed a similar BP reduction in 24 h, day- and nighttime ambulatory BP as well as in office BP in patients with and without CKD at any time point up to 12 months. There was no safety signal related to RDN. In particular, we did not observe a significant eGFR decline in both CKD positive or negative patients. We conclude that RDN is an effective and safe treatment option for patients with hypertension and chronic kidney disease.

Clinical Utility of Short-Term Blood Pressure Measures to Inform Long-Term Blood Pressure Management.

Decisions about hypertension management are substantially influenced by blood pressure (BP) levels measured before and soon after starting BP lowering drugs. We aimed to assess the utility of short-term BP changes in individuals in terms of long-term treatment response. Post hoc analyses of 2 randomized trials with 4-to-6 weeks active run-in for all participants, followed by randomization to active BP lowering treatment (combination perindopril±indapamide) or placebo. We categorized individuals by degree of systolic BP (SBP) change during active run-in treatment and assessed associations with subsequent postrandomization placebo-corrected BP reduction, cardiovascular events, and tolerability. We included individuals with baseline BP ≥140/90 mm Hg from the PROGRESS trial (Perindopril Protection Against Recurrent Stroke Study; 4275 individuals with cerebrovascular disease) and ADVANCE trial (The Action in Diabetes and Vascular Disease: Preterax and Diamicron-MR Controlled Evaluation; 6610 individuals with diabetes). During the active run-in period, the proportion of participants with initial SBP changes in 4 categories (SBP increase, 0-9.9 mm Hg decrease, 10-19.9 mm Hg decrease, and ≥20 mm Hg decrease) were 17%, 27%, 28%, and 28% in PROGRESS and 21%, 22%, 24%, and 33% in ADVANCE. Randomization to active therapy achieved similar placebo-corrected long-term BP reductions across the 4 initial SBP change groups in both trials (P-values for heterogeneity >0.1). There was no significant difference in achieving BP <140/90 mm Hg at follow-up, major cardiovascular events, nor treatment tolerability according to the SBP change during active run-in period (all P-values >0.1). An individual's apparent BP change immediately after commencing therapy has limited clinical utility. Therefore, more emphasis should be given to use of evidence-based regimens and measures over the long-term to ensure sustained BP control. URL: https://www. gov; Unique identifier: NCT00145925.

Effects of Renal Denervation vs Sham in Resistant Hypertension After Medication Escalation

Although early trials of endovascular renal denervation (RDN) for patients with resistant hypertension (RHTN) reported inconsistent results, ultrasound RDN (uRDN) was found to decrease blood pressure (BP) vs sham at 2 months in patients with RHTN taking stable background medications in the Study of the ReCor Medical Paradise System in Clinical Hypertension (RADIANCE-HTN TRIO) trial. To report the prespecified analysis of the persistence of the BP effects and safety of uRDN vs sham at 6 months in conjunction with escalating antihypertensive medications. This randomized, sham-controlled, clinical trial with outcome assessors and patients blinded to treatment assignment, enrolled patients from March 11, 2016, to March 13, 2020. This was an international, multicenter study conducted in the US and Europe. Participants with daytime ambulatory BP of 135/85 mm Hg or higher after 4 weeks of single-pill triple-combination treatment (angiotensin-receptor blocker, calcium channel blocker, and thiazide diuretic) with estimated glomerular filtration rate (eGFR) of 40 mL/min/1.73 m2 or greater were randomly assigned to uRDN or sham with medications unchanged through 2 months. From 2 to 5 months, if monthly home BP was 135/85 mm Hg or higher, standardized stepped-care antihypertensive treatment starting with aldosterone antagonists was initiated under blinding to treatment assignment. uRDN vs sham procedure in conjunction with added medications to target BP control. Six-month change in medications, change in daytime ambulatory systolic BP, change in home systolic BP adjusted for baseline BP and medications, and safety. A total of 65 of 69 participants in the uRDN group and 64 of 67 participants in the sham group (mean [SD] age, 52.4 [8.3] years; 104 male [80.6%]) with a mean (SD) eGFR of 81.5 (22.8) mL/min/1.73 m2 had 6-month daytime ambulatory BP measurements. Fewer medications were added in the uRDN group (mean [SD], 0.7 [1.0] medications) vs sham (mean [SD], 1.1 [1.1] medications; P = .045) and fewer patients in the uRDN group received aldosterone antagonists at 6 months (26 of 65 [40.0%] vs 39 of 64 [60.9%]; P = .02). Despite less intensive standardized stepped-care antihypertensive treatment, mean (SD) daytime ambulatory BP at 6 months was 138.3 (15.1) mm Hg with uRDN vs 139.0 (14.3) mm Hg with sham (additional decreases of -2.4 [16.6] vs -7.0 [16.7] mm Hg from month 2, respectively), whereas home SBP was lowered to a greater extent with uRDN by 4.3 mm Hg (95% CI, 0.5-8.1 mm Hg; P = .03) in a mixed model adjusting for baseline and number of medications. Adverse events were infrequent and similar between groups. In this study, in patients with RHTN initially randomly assigned to uRDN or a sham procedure and who had persistent elevation of BP at 2 months after the procedure, standardized stepped-care antihypertensive treatment escalation resulted in similar BP reduction in both groups at 6 months, with fewer additional medications required in the uRDN group. ClinicalTrials.gov Identifier: NCT02649426.

Effect of amlodipine versus bisoprolol in hypertensive patients on maintenance hemodialysis: A randomized controlled trial.

Background:Left ventricular hypertrophy and asymmetric dimethylarginine (ADMA) are surrogate markers of cardiovascular disease (CVD) in the dialysis population. This study aimed to evaluate the effect of a calcium channel blocker-based antihypertensive regimen compared to a beta-blocker-based antihypertensive regimen on left ventricular mass index (LVMI) and ADMA levels in hypertensive patients on hemodialysis (HD).Methods:This was a parallel-design, open-label, single-center randomized controlled trial on 46 hypertensive patients on maintenance HD, with no history of CVD. Patients were randomly assigned to receive amlodipine 10 mg/d (n = 23) or bisoprolol 10 mg/d (n = 23). Office-based blood pressure (BP) was targeted to ≤ 140/ 90 mm Hg. The outcome was the change in LVMI and ADMA from baseline to 6 months.Results:Baseline demographic and clinical characteristics did not vary between groups. After 6 months of treatment, amlodipine-based therapy induced a greater reduction in LVMI from baseline than bisoprolol-based treatment (35 ± 34.2 vs 9.8 ± 35.9 gm/m2; P = .017). A similar reduction in the mean BP occurred with treatment in both groups. ADMA concentration decreased significantly from baseline in the amlodipine group (0.75 ± 0.73 to 0.65 ± 0.67 nmol/mL; P = .001), but increased nonsignificantly in the bisoprolol group (0.64 ± 0.61 to 0.78 ± 0.64 nmol/mL; P = .052).Conclusion:This study showed that compared to a bisoprolol-based regimen, an amlodipine-based antihypertensive regimen resulted in a significantly greater reduction in LVMI and ADMA levels from baseline in hypertensive patients on HD despite similar BP reduction in both groups. These findings support the re-evaluation of amlodipine as a potential first-line antihypertensive treatment in patients on HD without previous CVD.Trial Registration:Clinicaltrials.gov Identifier: NCT04085562, registered September 2019.

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

High-Intensity Interval Training for Hypertension

Apply It! This article explores the frequency, intensity, time, and type framework within the context of HIIT, the unique elements of HIIT (e.g., intensity and work-to-recovery ratio), and concludes with examples of HIIT exercise regimens. By reading this article, health and fitness professionals will be reminded of the following takeaways: • HTN develops gradually and is generally the product of lifestyle choices concerning diet and exercise. • Although HTN is routinely treated with pharmacological intervention, lifestyle intervention is a primary therapeutic option for those newly diagnosed with hypertension. • Research supports the implementation of aerobically based HIIT and MICT for inducing similar reductions in systolic blood pressure and diastolic blood pressure in adults with pre-HTN and/or HTN. • HIIT for any client must be introduced gradually — and deliberately — over time. The introduction of HIIT should start with a single, brief set of HIIT (e.g., a few minutes of HIIT) to evaluate the client’s readiness and receptivity to the approach.

Renal denervation in hypertension patients: Proceedings from an expert consensus roundtable cosponsored by SCAI and NKF.

Renal denervation in hypertension patients: Proceedings from an expert consensus roundtable cosponsored by SCAI and NKF.