Renal denervation in treatment-resistant essential hypertension. A randomized, SHAM-controlled, double-blinded 24-h blood pressure-based trial.

BACKGROUND: Renal denervation (RDN), treating resistant hypertension, has, in open trial design, been shown to lower blood pressure (BP) dramatically, but this was primarily with respect to office BP. METHOD: We conducted a SHAM-controlled, double-blind, randomized, single-center trial to establish efficacy data based on 24-h ambulatory BP measurements (ABPM). Inclusion criteria were daytime systolic ABPM at least 145 mmHg following 1 month of stable medication and 2 weeks of compliance registration. All RDN procedures were carried out by an experienced operator using the unipolar Medtronic Flex catheter (Medtronic, Santa Rosa, California, USA). RESULTS: We randomized 69 patients with treatment-resistant hypertension to RDN (n = 36) or SHAM (n = 33). Groups were well balanced at baseline. Mean baseline daytime systolic ABPM was 159 ±â€Š12 mmHg (RDN) and 159 ±â€Š14 mmHg (SHAM). Groups had similar reductions in daytime systolic ABPM compared with baseline at 3 months [-6.2 ±â€Š18.8 mmHg (RDN) vs. -6.0 ±â€Š13.5 mmHg (SHAM)] and at 6 months [-6.1 ±â€Š18.9 mmHg (RDN) vs. -4.3 ±â€Š15.1 mmHg (SHAM)]. Mean usage of antihypertensive medication (daily defined doses) at 3 months was equal [6.8 ±â€Š2.7 (RDN) vs. 7.0 ±â€Š2.5 (SHAM)].RDN performed at a single center and by a high-volume operator reduced ABPM to the same level as SHAM treatment and thus confirms the result of the HTN3 trial. CONCLUSION: Further, clinical use of RDN for treatment of resistant hypertension should await positive results from double-blinded, SHAM-controlled trials with multipolar ablation catheters or novel denervation techniques.

[Research at regional hospitals in Denmark can be reinforced]. / Forskning på regionshospitaler kan styrkes.

We examined the conditions for health research at regional hospitals in Denmark. The study was conducted as an interview-based case study containing interviews with key persons at the governing level as well as medical doctors at the operating level. The results showed that the settings and opportunities regarding health research vary between university hospitals and non-university regional hospitals. However our findings indicate, that focusing on a long-term strategy to implement health research in regional hospitals will enable these to be more active in health research.

[Research in regional hospitals in two Danish regions]. / Forskning på regionshospitaler i Region Midtjylland og Region Nordjylland.

The quantity of interest, experience, and barriers to research in non-university hospitals in Denmark is undocumented. Therefore, a questionnaire was distributed to all employees at non-university hospitals in two Danish regions. The results showed that a substantial number of medical doctors were engaged in ongoing research. 24% of the respondents were supervisors in research projects, and 19% conducted contract research. Thus, Danish non-university hospitals have employees with both interest and experience in medical research. The four most commonly stated barriers for research were lack of time, funding, supervision, and training courses.

Catheter-based renal denervation for treatment of resistant hypertension.

INTRODUCTION: Activation of renal sympathetic nerves is associated with the development of hypertension. Catheter-based renal sympathetic denervation with radiofrequency energy ablation is a new promising treatment option for resistant hypertension. We here report the first Danish experiences and results with this technique. MATERIAL AND METHODS: Nine patients with resistant hypertension and a day-time 24-hour ambulatory blood pressure (BP) of 152/89 mmHg ± 10/10 (standard deviation) mmHg despite treatment with 5.4 ± 1.4 anti-hypertensive drugs underwent catheter-based renal sympathetic denervation with the Symplicity catheter. RESULTS: No periprocedural complications or adverse events during follow-up were observed. Seven patients received complete ablation and two patients only partial ablation. Five patients responded to the treatment with a reduction in day-time 24-hour ambulatory BP from 158/94 ± 13/9 mmHg to 139/82 ± 10/8 mmHg (p < 0.05) at the one month follow-up and a reduction in the number of anti-hypertensive drugs from 5.4 ± 1.6 to 3.4 ± 0.9 (p < 0.05). BP in the remaining four patients was not significantly changed and antihypertensive therapy was not changed. CONCLUSION: Catheter-based renal sympathetic denervation is a feasible and in several cases also effective treatment option for patients with resistant hypertension. Adequately designed controlled trials are needed to assess the long-term safety and the full potential of this treatment.

A substantial number of scientific publications originate from non-university hospitals.

INTRODUCTION: As we found no recent published reports on the amount and kind of research published from Danish hospitals without university affiliation, we have found it relevant to conduct a bibliometric survey disclosing these research activities. MATERIAL AND METHODS: We retrieved all scientific papers published in the period 2000-2009 emanating from all seven Danish non-university hospitals in two regions, comprising 1.8 million inhabitants, and which were registered in a minimum of one of the three databases: PubMed MEDLINE, Thomson Reuters Web of Science and Elsevier's Scopus. RESULTS: In 878 of 1,252 papers, the first and/or last author was affiliated to a non-university hospital. Original papers made up 69% of these publications versus 86% of publications with university affiliation on first or last place. Case reports and reviews most frequently had authors from regional hospitals as first and/or last authors. The total number of publications from regional hospitals increased by 48% over the 10-year period. Publications were cited more often if the first or last author was from a university hospital and even more so if they were affiliated to foreign institutions. Cardiology, gynaecology and obstetrics, and environmental medicine were the three specialities with the largest number of regional hospital publications. CONCLUSION: A substantial number of scientific publications originate from non-university hospitals. Almost two thirds of the publications were original research published in international journals. Variations between specialities may reflect local conditions. FUNDING: not relevant. TRIAL REGISTRATION: not relevant.

Long-term safety and tolerability of the oral direct renin inhibitor aliskiren with optional add-on hydrochlorothiazide in patients with hypertension: a randomized, open-label, parallel-group, multicentre, dose-escalation study with an extension phase.

BACKGROUND: Most patients with hypertension will require combination therapy with at least two agents from different antihypertensive classes to achieve blood pressure (BP) control. Thiazide diuretics, such as hydrochlorothiazide (HCTZ), are widely used in combination therapy. The volume reduction with these agents stimulates the renin-angiotensin system (RAS), making RAS inhibitors such as the direct renin inhibitor aliskiren a logical choice for combination therapy with HCTZ. OBJECTIVE: The aim of this study was to investigate the long-term safety, tolerability and efficacy of the direct renin inhibitor aliskiren, with or without addition of the diuretic HCTZ. METHODS: In the 12-month core study, patients with hypertension (mean sitting diastolic BP ≥90 mmHg and <110 mmHg) were randomized in a 3 : 2 ratio to once-daily aliskiren 150 mg or 300 mg. At months 2, 3, 4, 6 and 9, treatment was adjusted in patients not achieving a BP goal of <140/90 mmHg. Patients not at goal on aliskiren 150 mg once daily were up-titrated to aliskiren 300 mg once daily. Patients not at goal with aliskiren 300 mg once daily received add-on HCTZ 12.5 mg once daily, which was up-titrated to 25 mg once daily if BP remained inadequately controlled. At month 12, patients who received aliskiren/HCTZ 300 mg/25 mg once daily for at least 8 months in the core study were eligible to enter a 4-month extension study. RESULTS: Overall, 1625/1955 patients completed the core study, and 870/1955 patients received add-on HCTZ; 189/198 patients completed the 4-month extension. Aliskiren, with or without add-on HCTZ, was generally well tolerated; the incidence of adverse events (AEs) during the core study was similar among the four final treatment groups. The most frequently reported AEs in the core and extension studies were mild and transient cases of nasopharyngitis, headache and dizziness. Few patients exhibited laboratory abnormalities. Overall, aliskiren, with or without add-on HCTZ, reduced mean BP by 18.0/12.7 mmHg at core study endpoint, and 61.2% of patients achieved BP control. BP reductions with aliskiren/HCTZ 300 mg/25 mg combination therapy at the core study endpoint were maintained during the extension study. CONCLUSION: In patients with hypertension, long-term treatment with aliskiren, with or without add-on HCTZ, is well tolerated and provides effective BP lowering that is sustained over 12 months.

[The effect of calcium channel blockers for hypertension--a survey of a Cochrane review]. / Effekten af calciumantagonister ved hypertension--en gennemgang af et Cochranereview.

The Cochrane analysis comprises data from 18 trials with a total of 140,000 patients. Calcium channel blockers (CCBs) were superior to beta-blockers on stroke reduction. CCBs were also superior to angiotensin-converting enzyme inhibitors and angiotensin receptor blockers on stroke reduction, most likely explained by differences in achieved blood pressure. We question the conclusion, that diuretics are superior to CCBs as agents of first choice, but the analysis supports the view taken by many guidelines, that beta-blockers no longer are drugs of first choice.

[A survey of research funding at Danish regional hospitals]. / Forskning ved regionale hospitalsenheder i Vestdanmark.

INTRODUCTION: According to recently passed Danish legislation, all Danish hospitals are obliged to take part in scientific research. As data on financial support for research activities are lacking, we assessed the resources allocated to research from the budget of the central hospital management as a percentage of the total budget at Danish regional hospitals in 2007. MATERIAL AND METHODS: A postal survey was conducted at 13 hospitals in the Western part of Denmark. The questionnaire comprised items in the following major categories: 1) budget allocated specifically for research and travel grants; 2) employment of scientific and technical support staff; 3) facilities and equipment for research; and 4) research dissemination. RESULTS: Questionnaires were returned from 11 hospitals. Six hospitals reported to have dedicated fixed amounts on the budget for research, exact figures were reported in four cases only equivalent to 0.1%, 0.3%, 0.3% and 0.6% of the total budget. Most hospitals had associate professors, but only five had full professors. Seven hospitals supplied laboratories and technical facilities, eight hospitals held staff-meetings on a regular basis and four published an annual report on research activities. CONCLUSION: In the majority of regional hospitals in Western Denmark, less than 0.3% of the total budget administered by the central hospital management was allocated specifically for research. These figures, however, may not be accurate as individual departments may allocate additional resources from local budgets. We recommend that regional hospitals define research strategies and allocate the necessary funding in their budgets.

Small artery structure is an independent predictor of cardiovascular events in essential hypertension.

OBJECTIVE: Structural abnormality of resistance arteries is a characteristic pathophysiological phenomenon in essential hypertension and can be assessed in vitro as an increase in the media: lumen ratio (M: L) of isolated small arteries. We have investigated whether M: L is a risk predictor in uncomplicated essential hypertensive patients. Recently, high M: L was demonstrated as a prognostic marker in patients at high cardiovascular risk, including normotensive type 2 diabetic patients. Since diabetes is associated with pressure-independent changes in M: L, the relevance of this finding to essential hypertension has been uncertain. METHODS: We conducted a follow-up survey of 159 essential hypertensive patients, who had previously been submitted to a M: L evaluation while participating in a clinical trial. They composed a homogeneous moderate-risk group, with no concomitant diseases, and represented 1661 years of follow-up. RESULTS: Thirty patients suffered a documented predefined cardiovascular event during follow-up. Increased relative risk (RR) was associated with M: L >or= 0.083 (mean level of the hypertensive cohort), RR = 2.34 [95% confidence interval (CI) 1.11-4.95], and with M: L >or= 0.098 (mean level of a normotensive control group + 2SD), RR = 2.49 (95% CI 1.21-5.11). Both results remained significant (RR = 2.19, 95% CI 1.04-4.64, and RR = 2.20, 95% CI 1.06-4.56, respectively) when adjusted for Heart Score level (10-year mortality risk-estimate, integrating age, gender, systolic blood pressure, cholesterol and smoking). CONCLUSION: Abnormal resistance artery structure independently predicts cardiovascular events in essential hypertensive patients at moderate risk.