Catheter-Based Renal Sympathetic Denervation for Resistant Hypertension Durability of Blood Pressure Reduction Out to 24 Months

Renal sympathetic hyperactivity is seminal in the maintenance and progression of hypertension. Catheter-based renal sympathetic denervation has been shown to significantly reduce blood pressure (BP) in patients with hypertension. Durability of effect beyond 1 year using this novel technique has never been reported. A cohort of 45 patients with resistant hypertension (systolic BP GT = 160 mm Hg on GT = 3 antihypertension drugs, including a diuretic) has been originally published. Herein, we report longer-term follow-up data on these and a larger group of similar patients subsequently treated with catheter-based renal denervation in a nonrandomized manner. We treated 153 patients with catheter-based renal sympathetic denervation at 19 centers in Australia, Europe, and the United States. Mean age was 57 +/- 11 years, 39% were women, 31% were diabetic, and 22% had coronary artery disease. Baseline values included mean office BP of 176/98 +/- 17/15 mm Hg, mean of 5 antihypertension medications, and an estimated glomerular filtration rate of 83 +/- 20 mL/min per 1.73 m(2). The median time from first to last radiofrequency energy ablation was 38 minutes. The procedure was without complication in 97% of patients (149 of 153). The 4 acute procedural complications included 3 groin pseudoaneurysms and 1 renal artery dissection, all managed without further sequelae. Postprocedure office BPs were reduced by 20/10, 24/11, 25/11, 23/11, 26/14, and 32/14 mm Hg at 1, 3, 6, 12, 18, and 24 months, respectively. In conclusion, in patients with resistant hypertension, catheter-based renal sympathetic denervation results in a substantial reduction in BP sustained out to GT = 2 years of follow-up, without significant adverse events. (Hypertension. 2011;57:911-917.

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

Adding 6 months of androgen deprivation therapy to postoperative radiotherapy for prostate cancer: a comparison of short-course versus no androgen deprivation therapy in the RADICALS-HD randomised controlled trial

Background Previous evidence indicates that adjuvant, short-course androgen deprivation therapy (ADT) improves metastasis-free survival when given with primary radiotherapy for intermediate-risk and high-risk localised prostate cancer. However, the value of ADT with postoperative radiotherapy after radical prostatectomy is unclear. Methods RADICALS-HD was an international randomised controlled trial to test the efficacy of ADT used in combination with postoperative radiotherapy for prostate cancer. Key eligibility criteria were indication for radiotherapy after radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to radiotherapy alone (no ADT) or radiotherapy with 6 months of ADT (short-course ADT), using monthly subcutaneous gonadotropin-releasing hormone analogue injections, daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as distant metastasis arising from prostate cancer or death from any cause. Standard survival analysis methods were used, accounting for randomisation stratification factors. The trial had 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 80% to 86% (hazard ratio [HR] 0·67). Analyses followed the intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov, NCT00541047. Findings Between Nov 22, 2007, and June 29, 2015, 1480 patients (median age 66 years [IQR 61–69]) were randomly assigned to receive no ADT (n=737) or short-course ADT (n=743) in addition to postoperative radiotherapy at 121 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 9·0 years (IQR 7·1–10·1), metastasis-free survival events were reported for 268 participants (142 in the no ADT group and 126 in the short-course ADT group; HR 0·886 [95% CI 0·688–1·140], p=0·35). 10-year metastasis-free survival was 79·2% (95% CI 75·4–82·5) in the no ADT group and 80·4% (76·6–83·6) in the short-course ADT group. Toxicity of grade 3 or higher was reported for 121 (17%) of 737 participants in the no ADT group and 100 (14%) of 743 in the short-course ADT group (p=0·15), with no treatment-related deaths. Interpretation Metastatic disease is uncommon following postoperative bed radiotherapy after radical prostatectomy. Adding 6 months of ADT to this radiotherapy did not improve metastasis-free survival compared with no ADT. These findings do not support the use of short-course ADT with postoperative radiotherapy in this patient population

Duration of androgen deprivation therapy with postoperative radiotherapy for prostate cancer: a comparison of long-course versus short-course androgen deprivation therapy in the RADICALS-HD randomised trial

Background Previous evidence supports androgen deprivation therapy (ADT) with primary radiotherapy as initial treatment for intermediate-risk and high-risk localised prostate cancer. However, the use and optimal duration of ADT with postoperative radiotherapy after radical prostatectomy remains uncertain. Methods RADICALS-HD was a randomised controlled trial of ADT duration within the RADICALS protocol. Here, we report on the comparison of short-course versus long-course ADT. Key eligibility criteria were indication for radiotherapy after previous radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to add 6 months of ADT (short-course ADT) or 24 months of ADT (long-course ADT) to radiotherapy, using subcutaneous gonadotrophin-releasing hormone analogue (monthly in the short-course ADT group and 3-monthly in the long-course ADT group), daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as metastasis arising from prostate cancer or death from any cause. The comparison had more than 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 75% to 81% (hazard ratio [HR] 0·72). Standard time-to-event analyses were used. Analyses followed intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov , NCT00541047 . Findings Between Jan 30, 2008, and July 7, 2015, 1523 patients (median age 65 years, IQR 60–69) were randomly assigned to receive short-course ADT (n=761) or long-course ADT (n=762) in addition to postoperative radiotherapy at 138 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 8·9 years (7·0–10·0), 313 metastasis-free survival events were reported overall (174 in the short-course ADT group and 139 in the long-course ADT group; HR 0·773 [95% CI 0·612–0·975]; p=0·029). 10-year metastasis-free survival was 71·9% (95% CI 67·6–75·7) in the short-course ADT group and 78·1% (74·2–81·5) in the long-course ADT group. Toxicity of grade 3 or higher was reported for 105 (14%) of 753 participants in the short-course ADT group and 142 (19%) of 757 participants in the long-course ADT group (p=0·025), with no treatment-related deaths. Interpretation Compared with adding 6 months of ADT, adding 24 months of ADT improved metastasis-free survival in people receiving postoperative radiotherapy. For individuals who can accept the additional duration of adverse effects, long-course ADT should be offered with postoperative radiotherapy. Funding Cancer Research UK, UK Research and Innovation (formerly Medical Research Council), and Canadian Cancer Society

Patient perspectives on treatment adherence in hypertension: Preliminary results of an ESH survey in five countries

OBJECTIVE: The ESH Working group on Lifestyle, Cardiovascular Therapy and Adherence, in partnership with Servier, has developed a web-based questionnaire in different languages to investigate patients' perspectives on hypertension and treatment adherence. The objective of this survey was to decipher patients' perception, motivations and barriers to drug treatment adherence in hypertension. DESIGN AND METHOD: Eligible participants were men and women aged > 18 years, living in France, Germany, Italy, Spain and UK, with a diagnosis of hypertension made by a physician and internet access. Data were collected through patients' websites and organizations from January to March 2022. RESULTS: We included 595 participants (329 women, 55.3%, mean age 65 y); 72% were hypertensive for > 5 years, 93% were treated with antihypertensive medications for > 3 months and 50% had uncontrolled (140/90 mmHg) office BP at 3 months. The median number of all medications taken every day was 4 of which 2 were antihypertensive drugs. On a 10-point Likert scale, participants reported a modest impact of hypertension on their quality of life (3) or social and family life (3.1). The median level of stress was 5.2. In 76.6% of participants home BP was measured several times weekly (25%) or monthly (31%) or more. Antihypertensive medications were stopped unintentionally by 40% or taken irregularly by 44% of patients. The reasons for non-adherence to medications were forgetfulness (45%), side effects (17%) and running out of medications (15%). In 50% of cases, patients do not inform their physicians when stopping medications. The most useful approaches to support adherence reported by participants were single-pill combinations and smaller and cheaper pills. Information on hypertension and its treatment were considered sufficient for 33% of patients. CONCLUSIONS: In patients with internet access and willing to participate, our survey shows that despite having an uncontrolled office 3 month BP in 50% of them, participants report: 1) a modest impact of hypertension on their quality of life and a moderate level of anxiety, 2) frequent and usually non intentional non-adherence to prescribed antihypertensive medications, and 3) the necessity to improve the information provided to them

FREQUENCY OF MEDICAL OUT-PATIENT VISITS AND USE OF HOME BLOOD PRESSURE MONITORING IN HYPERTENSIVE PATIENTS IN FIVE EUROPEAN COUNTRIES

Objective: We assessed the frequency of out-patient visits for hypertension and the use of home blood pressure monitoring (HBPM) in 5 European countries.Design and method: We used the data of a web-based questionnaire developed by the Working group on Lifestyle, Cardiovascular Therapy and Adherence to investigate patients’ perspectives on hypertension management. Eligible participants were adult men and women, living in France, Germany, Italy, Spain and UK, with a confirmed diagnosis of hypertension. Data were collected through patients’ organizations and internet from January to March 2022.Results: From January to March 2022, we included 2757 participants, 46% women, 94% older than 60 y, 71% with hypertension duration >5y, 95% (91% for >3 months) treated with a mean of 1.7 antihypertensive pills /day (all medications: 4.1 pills/day). The out-patient visit frequency was monthly in 3% of the participants, once every 1 to 3 months in 23%, once every 3 to 6 months in 28%, once every 6 to 12 months in 30%, and less than once a year in 13%. There was large between-country variability in visit frequency (e.g., once every 1 to 3 months: 5% in UK, 21% in Germany, and 42% France; once every 6 to 12 months: 47% in UK, 23% in Germany, and 13% in France). Overall, 67% of participants performed HBPM themselves and 13% with an external help. HBPM was done on a regular basis in most patients (17% every day, 26% several times a week, 35% several times a month) while 8% did HBPM only when not feeling well. HBPM was performed more frequently in Germany and less in UK. Patients at higher cardiovascular risk did HBPM more frequently.Conclusions: There are no strong evidence-based recommendations on the frequency of out-patient visits for hypertension during long-term follow-up. Our survey shows a large variability between European countries in the way patients are followed. Moreover, strong implementation of HBPM is found in all countries, but the ESH protocol is not strictly followed. Therefore, studies are needed to define the most cost-effective hypertension follow-up and ESH recommendations for HBPM should be reinforced.</p

Hypertension healthcare professional beliefs and behaviour regarding patient medication adherence: a survey conducted among European Society of Hypertension Centres of Excellence.

Little is known on the beliefs, perceptions and practices of hypertension specialists in addressing non-adherence to therapy. Therefore, a survey was undertaken amongst healthcare professionals (HCPs) managing hypertension in the European Society of Hypertension (ESH) Centres of Excellence. Cross-sectional data were obtained between December 2020 and April 2021 using an online anonymous structured questionnaire including 26 questions/136 items, that was sent to all ESH Excellence centres. Overall 67 from 187 centres (37.3%) responded and 200 HCPs from 30 countries answered the questionnaire. Participants (60% men) were mainly physicians (91%) and nurses (8%) from University hospitals (77%). Among physicians, 83% had &gt;10 years professional experience. Average time dedicated to discuss medications was 1-5 min in 48% and 6-10 min in 29% of cases. Interviews with patients about adherence were the most frequently used assessment method. Chemical detection of medications in urine was available in 36% of centres. One third of physicians involved their patients regularly in treatment decisions. The most frequent methods to improve adherence included simplification of medication therapy, more frequent visits, and home blood pressure monitoring. The level of implementation of tools to detect and improve adherence in hypertension management by HCPs in ESH excellence centres is low. Structured educational activities focussing on adherence management and access to the newest objective measures to detect non-adherence might improve these deficits

Is the excess cardiovascular morbidity in pheochromocytoma related to blood pressure or to catecholamines?

Item does not contain fulltextBackground: It is generally accepted that pheochromocytoma is associated with an increased cardiovascular risk. This is however not based on studies with an appropriate control group of patients with essential hypertension. Aim of the Study: We examined whether patients with pheochromocytoma have an excess cardiovascular morbidity as compared to hypertensive patients. Methods: In a retrospective case-control study we reviewed the medical charts of 109 pheochromocytoma patients for cardiovascular events within 5 years prior to the diagnosis. These patients were matched to control patients with essential hypertension for gender and year of birth and diagnosis. Outcome variables were ischemic heart disease, cerebrovascular accidents, and transient ischemic attacks. Classical cardiovascular risk factors were also assessed. Results: A significantly higher rate of patients with pheochromocytoma suffered a cardiovascular event (13.8%; 95% confidence interval: 7.9%-21.6%) as compared to hypertensive patients (1.1%, 95% confidence interval: 0.1%-3.9%) (P < .001). Blood pressure level was lower in pheochromocytoma patients (153/91 +/- 35/15 mm Hg) than in hypertensive patients (170/103 +/- 18/8 mm Hg) (P < .001), even after correction for use of antihypertensive medication (P < .02). The difference in event rates could not be attributed to differences in other cardiovascular risk factors. Conclusions: Pheochromocytoma patients have a clearly higher rate of cardiovascular events than patients with essential hypertension. This cannot be attributed to differences in blood pressure or other cardiovascular risk factors. The most likely explanation for the excess event rate is the prolonged exposure to the toxic effects of tumoral catecholamines. These data underpin the importance of a timely diagnosis and treatment of pheochromocytoma

Adrenal vein sampling versus CT scan to determine treatment in primary aldosteronism: an outcome-based randomised diagnostic trial

Background The distinction between unilateral aldosterone-producing adenoma or bilateral adrenal hyperplasia as causes of primary aldosteronism is usually made by adrenal CT or by adrenal vein sampling (AVS). Whether CT or AVS represents the best test for diagnosis remains unknown. We aimed to compare the outcome of CT-based management with AVS-based management for patients with primary aldosteronism. Methods In a randomised controlled trial, we randomly assigned patients with aldosteronism to undergo either adrenal CT or AVS to determine the presence of aldosterone-producing adenoma (with subsequent treatment consisting of adrenalectomy) or bilateral adrenal hyperplasia (subsequent treatment with mineralocorticoid receptor antagonists). The primary endpoint was the intensity of drug treatment for obtaining target blood pressure after 1 year of follow-up, in the intention-to-diagnose population. Intensity of drug treatment was expressed as daily defined doses. Key secondary endpoints included biochemical outcome in patients who received adrenalectomy, health-related quality of life, cost-effectiveness, and adverse events. This trial is registered with ClinicalTrials.gov, number NCT01096654. Findings We recruited 200 patients between July 6, 2010, and May 30, 2013. Of the 184 patients that completed follow-up, 92 received CT-based treatment (46 adrenalectomy and 46 mineralocorticoid receptor antagonist) and 92 received AVS-based treatment (46 adrenalectomy and 46 mineralocorticoid receptor antagonist). We found no differences in the intensity of antihypertensive medication required to control blood pressure between patients with CT-based treatment and those with AVS-based treatment (median daily defined doses 3.0 [IQR 1.0-5.0] vs 3.0 [1.1-5.9], p=0.52; median number of drugs 2 [IQR 1-3] vs 2 [1-3], p=0.87). Target blood pressure was reached in 39 (42%) patients and 41 (45%) patients, respectively (p=0.82). On secondary endpoints we found no differences in health-related quality of life (median RAND-36 physical scores 52.7 [IQR 43.9-56.8] vs 53.2 [44.0-56.8], p=0.83; RAND-36 mental scores 49.8 [43.1-54.6] vs 52.7 [44.9-55.5], p=0.17) for CT-based and AVS-based treatment. Biochemically, 37 (80%) of patients with CT-based adrenalectomy and 41 (89%) of those with AVS-based adrenalectomy had resolved hyperaldosteronism (p=0.25). A non-significant mean difference of 0.05 (95% CI -0.04 to 0.13) in quality-adjusted life-years (QALYs) was found to the advantage of the AVS group, associated with a significant increase in mean health-care costs of (sic)2285 per patient (95% CI 1323-3248). At a willingness-to-pay value of (sic)30 000 per QALY, the probability that AVS compared with CT constitutes an efficient use of health-care resources in the diagnostic work-up of patients with primary aldosteronism is less than 0.2. There was no difference in adverse events between groups (159 events of which nine were serious vs 187 events of which 12 were serious) for CT-based and AVS-based treatment. Interpretation Treatment of primary aldosteronism based on CT or AVS did not show significant differences in intensity of antihypertensive medication or clinical benefits for patients after 1 year of follow-up. This finding challenges the current recommendation to perform AVS in all patients with primary aldosteronism