Hypophosphataemia risk associated with ferric carboxymaltose in heart failure: A pooled analysis of clinical trials.

Aims: Iron deficiency is a common finding among patients with heart failure (HF) and is associated with adverse outcomes, including decreased quality of life, increased risk of hospitalization, and decreased survival. Intravenous ferric carboxymaltose (FCM) has been shown to improve outcomes among patients with HF and concomitant iron deficiency, but FCM is associated with an increased risk of hypophosphataemia. We aimed to better characterize this risk among HF populations.

Medical Treatment of Heart Failure with Reduced Ejection Fraction in the Elderly.

The aging population, higher burden of predisposing conditions and comorbidities along with improvements in therapy all contribute to the growing prevalence of heart failure (HF). Although the majority of trials have not demonstrated age-dependent heterogeneity in the efficacy or safety of medical treatment for HF, the latest trials demonstrate that older participants are less likely to receive established drug therapies for HF with reduced ejection fraction. There remains reluctance in real-world clinical practice to prescribe and up-titrate these medications in older people, possibly because of (mis)understanding about lower tolerance and greater propensity for developing adverse drug reactions.

Efficacy and Safety of Novel Aspirin Formulations: A Randomized, Double-Blind, Placebo-Controlled Study.

Low-dose aspirin represents the best option in the secondary prevention of coronary artery disease, but its extensive use in primary prevention is limited by the occurrence of gastric mucosal lesions and increased risk of bleeding. We investigated the safety profile of a novel sublingual aspirin formulation in 200 healthy volunteers, randomly assigned to ten ( = 20 each) different 7-day once-daily treatment regimens. Gastric mucosal injury based on the modified Lanza score (MLS), the histopathology of gastric mucosa and the serum determination of thromboxane B (TXB) and urinary 11-dehydro-TXB levels were evaluated at basal as well as after 7 days of each placebo or aspirin treatment regimen.

Hyperkalemia and Renin-Angiotensin-Aldosterone System Inhibitors Dose Therapy in Heart Failure With Reduced Ejection Fraction.

Renin-angiotensin-aldosterone system inhibitors (RAASi) are known to improve outcomes in patients who have heart failure with reduced ejection fraction (HFrEF). To reduce mortality in these patients, RAASi should be uptitrated to the maximally tolerated dose. However, RAASi may also cause hyperkalemia.

Cardiovascular care of patients with stroke and high risk of stroke: The need for interdisciplinary action: A consensus report from the European Society of Cardiology Cardiovascular Round Table.

Comprehensive stroke care is an interdisciplinary challenge. Close collaboration of cardiologists and stroke physicians is critical to ensure optimum utilisation of short- and long-term care and preventive measures in patients with stroke. Risk factor management is an important strategy that requires cardiologic involvement for primary and secondary stroke prevention.

Frailty in Heart Failure: Implications for Management.

Frailty is a complex clinical syndrome associated with ageing and chronic illness, resulting from multiple organ impairment; physiological reserves decrease and vulnerability to stressors increase. The role of frailty in cardiovascular disease has become increasingly recognised. Up to 79% of patients with heart failure are frail.

Metabolic Modulation of Cardiac Metabolism in Heart Failure.

Heart failure (HF) is associated with metabolic changes that cause a progressive impairment of cardiac and skeletal muscle high-energy phosphate production. As a consequence of the impaired cardiac metabolism, other processes are activated in the failing heart that further exacerbate the progression of HF. The reduced production of high-energy phosphates has important implications for both systole and diastole in HF with both preserved and reduced left ventricular function.

Pharmacological Interventions Effective in Improving Exercise Capacity in Heart Failure.

Heart failure (HF) is characterised by exercise intolerance, which substantially impairs quality of life (QOL) and prognosis. The aim of this review is to summarise the state of the art on pharmacological interventions that are able to improve exercise capacity in HF. Ivabradine, trimetazidine and intravenous iron are the only drugs included in the European Society of Cardiology HF guidelines that have consistently been shown to positively affect functional capacity in HF.

Heart failure with mid-range ejection fraction in CHARM: characteristics, outcomes and effect of candesartan across the entire ejection fraction spectrum.

Aims: We tested the hypothesis that candesartan improves outcomes in heart failure (HF) with mid-range ejection fraction [HFmrEF; ejection fraction (EF) 40-49%].

Methods And Results: In 7598 patients enrolled in the CHARM Programme (HF across the spectrum of EF), we assessed characteristics, outcomes and treatment effect of candesartan according to EF. Patients with HFmrEF (n = 1322, 17%) were similar to those with HF with reduced EF (HFrEF; n = 4323, 57%) with respect to some characteristics, and intermediate between HFrEF and HF with preserved EF (HFpEF; n = 1953, 26%) with respect to others.

Heart Failure in Patients with Diabetes Mellitus.

Diabetes and heart failure are closely related: patients with diabetes have an increased risk of developing heart failure and those with heart failure are at higher risk of developing diabetes. Furthermore, antidiabetic medications increase the risk of mortality and hospitalisation for heart failure in patients with and without pre-existing heart failure. When the two diseases are considered individually, heart failure has a much poorer prognosis than diabetes mellitus; therefore heart failure has to be a priority for treatment in patients presenting with the two conditions, and the diabetic patient with heart failure should be managed by the heart failure team.

Independent academic Data Monitoring Committees for clinical trials in cardiovascular and cardiometabolic diseases.

Data Monitoring Committees (DMCs) play a crucial role in the conducting of clinical trials to ensure the safety of study participants and to maintain a trial's scientific integrity. Generally accepted standards exist for DMC composition and operational conduct. However, some relevant issues are not specifically addressed in current guidance documents, resulting in uncertainties regarding optimal approaches for communication between the DMC, steering committee, and sponsors, release of information, and liability protection for DMC members.

Pharmacological reasons that may explain why randomized clinical trials have failed in acute heart failure syndromes.

Acute heart failure (AHF) represents a clinical challenge as it encloses a heterogeneous group of syndromes (AHFS) with different pathophysiology, clinical presentations, prognosis and response to therapy. In the last 25years multiple therapeutic targets have been identified and numerous new drugs were evaluated but, up to now, all failed to demonstrate a consistent benefit on clinical outcomes. Moreover, a repeated finding has been the poor correlation between the encouraging results of preclinical and early clinical trials and the lack of effect on outcomes observed in phase III trials.

Under-representation of elderly and women in clinical trials.

Background: Elderly and women have been often under-represented in randomised clinical trials (RCTs) testing the effect of treatments on cardiovascular diseases (CVDs) even though these diseases highly affect both of them.

Aims: Taking into account these issues, the aim of this review is to critically analyse the topic of under-representation of elderly and women in cardiovascular RCTs.

Conclusions: Compared to their younger counterparts, elderly have a higher incidence of disease-related morbidities, take more medicines and account for more adverse drug related events.

Reductions in N-Terminal Pro-Brain Natriuretic Peptide Levels Are Associated With Lower Mortality and Heart Failure Hospitalization Rates in Patients With Heart Failure With Mid-Range and Preserved Ejection Fraction.

Background: In heart failure with mid-range ejection fraction (HFmrEF) and preserved ejection fraction (HFpEF), feasible surrogate end points are needed for phase II trials. The aim was to assess whether a reduction in N-terminal pro-B-type natriuretic peptide (NT-proBNP) is associated with improved mortality/morbidity in an unselected population of HFmrEF and HFpEF patients.

Methods And Results: In the Swedish Heart Failure Registry, HFmrEF (EF=40%-49%) and HFpEF (EF≥50%) patients reporting at least 2 consecutive outpatient NT-proBNP assessments were prospectively studied.

Efficacy and Safety of Novel Oral Anticoagulants in Patients With Atrial Fibrillation and Heart Failure: A Meta-Analysis.

Objectives: This study investigated the efficacy and safety of novel oral anticoagulants (NOACs) in patients with atrial fibrillation (AF) and heart failure (HF) by a meta-analysis.

Background: AF is quite prevalent in patients with HF.

Methods: Four phase III clinical trials comparing NOACs to warfarin in patients with AF were included.

Pharmacokinetics and pharmacodynamics of cardiovascular drugs in chronic heart failure.

Pharmacotherapy in chronic heart failure (HF) is challenging, due to the diverse neuroendocrine, inflammatory, metabolic and immunological mechanisms involved in its pathogenesis, the presence of co-morbidities and use of multiple therapies. Further, physiological parameters influencing drug pharmacokinetics (PKs) and pharmacodynamics (PDs) may be altered in patients with HF. There is growing evidence that the disease-induced physiological changes may influence the PKs and PDs of all drugs used in patients with HF.

Greater cardiovascular risk reduction with once-daily fixed combination of three antihypertensive agents and statin versus free-drug combination: The ALL-IN-ONE trial.

Background: The ultimate goal of antihypertensive therapy is cardiovascular risk (CVR) reduction. The aim of this study was to compare the efficacy and safety of once-daily fixed combination (ODFC) versus free-drug combination (FDC) of 3antihypertensive agents and statin.

Methods: The ALL-IN-ONE trial was a 12-week randomized, prospective, multicenter trial.

Effects of Dipeptidyl Peptidase 4 Inhibitors and Sodium-Glucose Linked coTransporter-2 Inhibitors on cardiovascular events in patients with type 2 diabetes mellitus: A meta-analysis.

Background: Dipeptidyl Peptidase 4 Inhibitors (DPP4-I) and Sodium-Glucose Linked coTransporter-2 Inhibitors (SGLT2-I) improve glycemic control in patients with type 2 diabetes mellitus (DM). However, only few studies were designed to assess the efficacy and safety of these drugs on cardiovascular (CV) events and mortality. The purpose of the current study was to evaluate the effects of DPP4-Is and SGLT2-Is on CV events and mortality by meta-analysis.

Men with testosterone deficiency and a history of cardiovascular diseases benefit from long-term testosterone therapy: observational, real-life data from a registry study.

Background/objectives: Long-term testosterone therapy (TTh) in men with hypogonadism has been shown to improve all components of the metabolic syndrome. In this study, we investigated the effects of long-term TTh up to 8 years in hypogonadal men with a history of cardiovascular disease (CVD).

Patients And Methods: In two urological clinics observational registries, we identified 77 hypogonadal men receiving TTh who also had a history of CVD.

Report of the European Society of Cardiology Cardiovascular Round Table regulatory workshop update of the evaluation of new agents for the treatment of acute coronary syndrome: Executive summary.

Regulatory authorities interpret the results of randomized controlled trials according to published principles. The European Medicines Agency (EMA) is planning a revision of the 2000 and 2003 guidance documents on clinical investigation of new medicinal products for the treatment of acute coronary syndrome (ACS) to achieve consistency with current knowledge in the field. This manuscript summarizes the key output from a collaborative workshop, organized by the Cardiovascular Round Table and the European Affairs Committee of the European Society of Cardiology, involving clinicians, academic researchers, trialists, European and US regulators, and pharmaceutical industry researchers.