Effects of serelaxin in patients with acute heart failure

Background: Serelaxin is a recombinant form of human relaxin-2, a vasodilator hormone that contributes to cardiovascular and renal adaptations during pregnancy. Previous studies have suggested that treatment with serelaxin may result in relief of symptoms and in better outcomes in patients with acute heart failure. Methods: In this multicenter, double-blind, placebo-controlled, event-driven trial, we enrolled patients who were hospitalized for acute heart failure and had dyspnea, vascular congestion on chest radiography, increased plasma concentrations of natriuretic peptides, mild-to-moderate renal insufficiency, and a systolic blood pressure of at least 125 mm Hg, and we randomly assigned them within 16 hours after presentation to receive either a 48-hour intravenous infusion of serelaxin (30 μg per kilogram of body weight per day) or placebo, in addition to standard care. The two primary end points were death from cardiovascular causes at 180 days and worsening heart failure at 5 days. Results: A total of 6545 patients were included in the intention-to-treat analysis. At day 180, death from cardiovascular causes had occurred in 285 of the 3274 patients (8.7%) in the serelaxin group and in 290 of the 3271 patients (8.9%) in the placebo group (hazard ratio, 0.98; 95% confidence interval [CI], 0.83 to 1.15; P=0.77). At day 5, worsening heart failure had occurred in 227 patients (6.9%) in the serelaxin group and in 252 (7.7%) in the placebo group (hazard ratio, 0.89; 95% CI, 0.75 to 1.07; P=0.19). There were no significant differences between the groups in the incidence of death from any cause at 180 days, the incidence of death from cardiovascular causes or rehospitalization for heart failure or renal failure at 180 days, or the length of the index hospital stay. The incidence of adverse events was similar in the two groups. Conclusions: In this trial involving patients who were hospitalized for acute heart failure, an infusion of serelaxin did not result in a lower incidence of death from cardiovascular causes at 180 days or worsening heart failure at 5 days than placebo. (Funded by Novartis Pharma; RELAX-AHF-2 ClinicalTrials.gov number, NCT01870778. opens in new tab.

CHADS2 risk score and rate of stroke or systemic embolism and major bleeding in patients with non-valvular atrial fibrillation receiving non-vitamin K antagonist oral anticoagulants.

Randomized trials showed non-inferior or superior results of the non-vitamin K antagonist oral anticoagulants (NOACs) compared with warfarin in patients with non-valvular atrial fibrillation (AF). Despite the absence of direct head-to-head comparisons between the different NOACs, certain molecules have been proposed for subgroups of patients based mainly on the perception of different bleeding risks. The CHADS2 score has been uniformly used in the inclusion criteria of these studies and shared similar risk factors as the haemorrhagic risk score HAS-BLED. The aim of the present report was to highlight the relationships between CHADS2 score and the rate of stroke or systemic embolism, and the rate of major bleeding in patients with AF on treatment with NOACs. Overall, in all the available randomized studies, a fairly good continuous relationship was observed between the CHADS2 risk score and the rate of stroke or systemic embolism, and the rate of major bleeding in the different studies. Larger registries are needed to confirm this hypothesis

Centralized Pan-European survey on the undertreatment of hypercholesterolaemia (CEPHEUS).

The CEntralized Pan-European survey on tHE Under-treatment of hypercholeSterolaemia (CEPHEUS) was initiated to quantify the degree of under-treatment of hypercholesterolaemia in Europe. Its primary objective was to establish the proportion of treated patients reaching the LDL-C goals according to the Third Joint European Task Force guidelines. Secondary objectives targeted subgroups of primary or secondary prevention patients and those with a metabolic syndrome. Further-more, CEPHEUS also aimed at the identification of determinants for under-treatment. Among the patients available for evaluation in Belgium (n=6276), 58.5% reached LDL-C goals as recommended by the 2003 European guidelines, 59.8% in primary prevention, 55.8% in secondary prevention, and 55.8% of those with a metabolic syndrome. The majority of patients (82.5%) was treated with statins. The univariate significant (P < 0.10) predictors of attaining LDL-C goal were the following: (a) nonsmoker, (b) no history of PAD or CAD, (c) absence of metabolic syndrome, (d) lower CV risk category, (e) absence of patient's concerns about treatment changes, (f) no withdrawal of lipid-lowering therapy when on target, (g) optimal. treatment adherence, (h) no patient's frustrations, (i) lipid-monitoring frequency, (j) physician being a specialist and (k) physicians finding it stressful to get patients on target. In an adjusted multi-level model, achievement of the LDL-C goals was significantly associated with: (a) type of lipid-lowering therapy, (b) risk category the patient fell into, (c) LDL-C level before initiating treatment, (d) patient's feelings about the treatment, (e) patient's acknowledgement about current cholesterol level and (f) self-reported drug compliance

The common control of hypertension and therapeutic attitudes in belgium and luxemburg study (COME STAI)

Study aim The aim of this study was to assess hypertension management in general practice in Belgium and Luxembourg, shortly before the publication of the 2013 ESH/ESC Guidelines for arterial hypertension management. Methods A total of 516 general physicians evaluated 10,078 consecutive hypertensive patients. All used the same definitions to assess cardiovascular risk. Results Systolic (S) blood pressure (BP) was 139 ± 19 mmHg, diastolic (D) BP 80 ± 11 mmHg, patients were 64 ± 13 years old and their body mass index (BMI) was 28 ± 5 kg/m² (mean ± SD). Treatment remained unchanged in 71% of the patients with a SBP ≥ 140 mmHg. Those on ≥ 2 antihypertensive drugs were older, had higher BMI, slower HR, higher perceived cardiovascular risk, but lower BP (all P ≤ 0.001 vs no and monotherapy groups). Patients in whom treatment was intensified were at higher cardiovascular risk, as substantiated by an increased prevalence of males, a higher BP, a faster HR and a larger BMI (all P ≤ 0.0001). High cardiovascular risk patients underwent more frequent treatment simplifications with fixed-combination therapies or the addition of another antihypertensive class (all P ≤ 0.0001 vs not at high cardiovascular risk). Among the 523 patients older than 80 years with SBP ≥ 140 mmHg, treatment intensification occurred in 32% when SBP ≥ 150 mmHg, and in 10% when SBP was between 140 and 149 mmHg (P ≤ 0.0001). Conclusion The COME STAI study suggests that there is still room for improvement in hypertension control in Belgium and Luxembourg.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Efficacy of atorvastatin after LDL-cholesterol-based dose selection in high risk dyslipidaemic patients: Results of the target dose study

SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Self-expanding Transcatheter vs Surgical Aortic Valve Replacement in Intermediate-Risk Patients: 5-Year Outcomes of the SURTAVI Randomized Clinical Trial

Importance In patients with severe aortic valve stenosis at intermediate surgical risk, transcatheter aortic valve replacement (TAVR) with a self-expanding supra-annular valve was noninferior to surgery for all-cause mortality or disabling stroke at 2 years. Comparisons of longer-term clinical and hemodynamic outcomes in these patients are limited. Objective To report prespecified secondary 5-year outcomes from the Symptomatic Aortic Stenosis in Intermediate Risk Subjects Who Need Aortic Valve Replacement (SURTAVI) randomized clinical trial. Design, Setting, and Participants SURTAVI is a prospective randomized, unblinded clinical trial. Randomization was stratified by investigational site and need for revascularization determined by the local heart teams. Patients with severe aortic valve stenosis deemed to be at intermediate risk of 30-day surgical mortality were enrolled at 87 centers from June 19, 2012, to June 30, 2016, in Europe and North America. Analysis took place between August and October 2021. Intervention Patients were randomized to TAVR with a self-expanding, supra-annular transcatheter or a surgical bioprosthesis. Main Outcomes and Measures The prespecified secondary end points of death or disabling stroke and other adverse events and hemodynamic findings at 5 years. An independent clinical event committee adjudicated all serious adverse events and an independent echocardiographic core laboratory evaluated all echocardiograms at 5 years. Results A total of 1660 individuals underwent an attempted TAVR (n = 864) or surgical (n = 796) procedure. The mean (SD) age was 79.8 (6.2) years, 724 (43.6%) were female, and the mean (SD) Society of Thoracic Surgery Predicted Risk of Mortality score was 4.5% (1.6%). At 5 years, the rates of death or disabling stroke were similar (TAVR, 31.3% vs surgery, 30.8%; hazard ratio, 1.02 [95% CI, 0.85-1.22]; P = .85). Transprosthetic gradients remained lower (mean [SD], 8.6 [5.5] mm Hg vs 11.2 [6.0] mm Hg; P < .001) and aortic valve areas were higher (mean [SD], 2.2 [0.7] cm2 vs 1.8 [0.6] cm2; P < .001) with TAVR vs surgery. More patients had moderate/severe paravalvular leak with TAVR than surgery (11 [3.0%] vs 2 [0.7%]; risk difference, 2.37% [95% CI, 0.17%- 4.85%]; P = .05). New pacemaker implantation rates were higher for TAVR than surgery at 5 years (289 [39.1%] vs 94 [15.1%]; hazard ratio, 3.30 [95% CI, 2.61-4.17]; log-rank P < .001), as were valve reintervention rates (27 [3.5%] vs 11 [1.9%]; hazard ratio, 2.21 [95% CI, 1.10-4.45]; log-rank P = .02), although between 2 and 5 years only 6 patients who underwent TAVR and 7 who underwent surgery required a reintervention. Conclusions and Relevance Among intermediate-risk patients with symptomatic severe aortic stenosis, major clinical outcomes at 5 years were similar for TAVR and surgery. TAVR was associated with superior hemodynamic valve performance but also with more paravalvular leak and valve reinterventions

Final results of a phase IIa, randomised, open-label trial to evaluate the percutaneous intramyocardial transplantation of autologous skeletal myoblasts in congestive heart failure patients: the SEISMIC trial.

peer reviewedAIMS: The SEISMIC study was an open-label, prospective, randomised study to assess the safety and feasibility of percutaneous myoblast implantation in heart failure patients with implanted cardioverter-defibrillators (ICD). METHODS AND RESULTS: Patients were randomised 2:1 to autologous skeletal myoblast therapy vs. optimal medical treatment. The primary safety end-point was defined as the incidence of procedural and device related serious adverse events, whereas the efficacy endpoints were defined as the change in global LVEF by MUGA scan, change in NYHA classification of heart failure and in the distance achieved during a six-minute walk test (6MW) at 6-month follow-up. Forty subjects were randomised to the treatment arm (n=26), or to the control arm (n=14). There were 12 sustained arrhythmic events and one death after episodes of ventricular tachycardia (VT) in the treatment group and 14 events in the control group (P=ns). At 6-month follow-up, 6MW distance improved by 60.3+/-54.1?meters in the treated group as compared to no improvement in the control group (0.4+/-185.7?meters; P=ns). In the control group, 28.6% experienced worsening of heart failure status (4/14), while 14.3% experienced an improvement in NYHA classification (2/14). In the myoblast-treatment arm, one patient experienced a deterioration in NYHA classification (8.0%), whereas five patients improved one or two classes (20.0%; P=0.06). However, therapy did not improve global LVEF measured by MUGA at 6-month follow-up. CONCLUSIONS: These data indicate that implantation of myoblasts in patients with HF is feasible, appears to be safe and may provide symptomatic relief, though no significant effect was detected on global LVEF

A critical review on telemonitoring in heart failure

Morbidity and mortality remain high in heart failure despite considerable progress achieved with medical therapy and electrical devices. A multidisciplinary approach is actually strongly recommended. In order to provide optimal care to the ever-growing population of patients with heart failure, telemonitoring has been proposed as a modality to improve usual care. The aim of this review is to provide an overview of the existing evidence on telemonitoring in HF. Despite two major meta-analyses with favourable results, two recent, large, multicentre, randomized controlled trials, one with a sophisticated technical remote telemonitoring approach (TIM-HF) in stable chronic HF and the other with a comprehensive telephone-based interactive voice-response monitoring (Tele-HF) in patients recently hospitalized for heart failure, have been performed and both failed to demonstrate a clinical benefit for telemonitoring. Newer technologies or other modalities, such as collaboration between a general practitioner and a heart failure clinic facilitated by telemonitoring should be further evaluated. Dedicated telemonitoring for heart failure may be a practical adjunct in selective centres and patients, on top of usual care, including education and a multidisciplinary approach. However, prior to being accepted as a standard of care, more evidence from large, randomized clinical trials is required.status: publishe