Intravenous ferric carboxymaltose for iron repletion following acute heart failure in patients with and without diabetes: a subgroup analysis of the randomized AFFIRM-AHF trial.

Background: In AFFIRM-AHF, treatment of iron deficiency with intravenous ferric carboxymaltose (FCM) reduced the risk of heart failure (HF) hospitalization and improved quality of life (QoL) vs placebo in patients stabilized following an acute HF (AHF) episode, with no effect on cardiovascular (CV) death. Diabetes and iron deficiency frequently accompany AHF. This post hoc analysis explored the effects of diabetes on outcomes in AFFIRM-AHF patients.

Minimal Clinically Important Differences in 6-Minute Walk Test in Patients With HFrEF and Iron Deficiency.

Background: The 6-minute walk test (6MWT) is widely used to measure exercise capacity; however, the magnitude of change that is clinically meaningful for individuals is not well established in heart failure with reduced ejection fraction (HFrEF).

Objective: To calculate the minimal clinically important difference (MCID) for change in exercise capacity in the 6MWT in iron-deficient populations with HFrEF.

Methods: In this pooled secondary analysis of the FAIR-HF and CONFIRM-HF trials, mean changes in the 6MWT from baseline to weeks 12 and 24 were calculated and calibrated against the Patient Global Assessment (PGA) tool (clinical anchor) to derive MCIDs in improvement and deterioration.

Responder analysis for improvement in 6-min walk test with ferric carboxymaltose in patients with heart failure with reduced ejection fraction and iron deficiency.

Aim: Improving functional capacity is a key goal in heart failure (HF). This pooled analysis of FAIR-HF and CONFIRM-HF assessed the likelihood of improvement or deterioration in 6-min walk test (6MWT) among iron-deficient patients with chronic HF with reduced ejection fraction (HFrEF) receiving ferric carboxymaltose (FCM).

Methods And Results: Data for 760 patients (FCM: n = 454; placebo: n = 306) were analysed.

Health status improvement with ferric carboxymaltose in heart failure with reduced ejection fraction and iron deficiency.

Aim: Intravenous ferric carboxymaltose (FCM) has been shown to improve overall quality of life in iron-deficient heart failure with reduced ejection fraction (HFrEF) patients at a trial population level. This FAIR-HF and CONFIRM-HF pooled analysis explored the likelihood of individual improvement or deterioration in Kansas City Cardiomyopathy Questionnaire (KCCQ) domains with FCM versus placebo and evaluated the stability of this response over time.

Methods And Results: Changes versus baseline in KCCQ overall summary score (OSS), clinical summary score (CSS) and total symptom score (TSS) were assessed at weeks 12 and 24 in FCM and placebo groups.

Control of moderate-to-severe asthma with randomized ciclesonide doses of 160, 320 and 640 μg/day.

Background: The inhaled corticoteroid (ICS) ciclesonide (Cic), controls asthma symptoms in the majority of patients at the recommended dose of 160 µg/day. However, the relationship between the level of asthma control and increasing doses of Cic is unknown. This study investigated whether long-term treatment with higher doses of Cic would further improve asthma symptoms in patients with uncontrolled asthma despite ICS use.

Roflumilast combined with montelukast versus montelukast alone as add-on treatment in patients with moderate-to-severe asthma.

Background: Roflumilast, a selective phosphodiesterase 4 inhibitor, has been shown to provide modest improvements in lung function in patients with mild-to-moderate asthma, but its efficacy in patients with moderate-to-severe asthma has not been assessed. We hypothesized that this drug might provide benefit if combined with montelukast, a leukotriene receptor antagonist, in patients whose symptoms are uncontrolled by inhaled corticosteroids and long-acting β-agonists.

Objective: We sought to examine the efficacy, safety, and mode of action of the addition of roflumilast and montelukast versus montelukast alone in patients with moderate-to-severe asthma.

Effect of roflumilast on exacerbations in patients with severe chronic obstructive pulmonary disease uncontrolled by combination therapy (REACT): a multicentre randomised controlled trial.

Background: Roflumilast reduces exacerbations in patients with severe chronic obstructive pulmonary disease. Its effect in patients using fixed combinations of inhaled corticosteroids and longacting β2 agonists is unknown. We postulated that roflumilast would reduce exacerbations in patients with severe chronic obstructive pulmonary disease at risk for exacerbations, even in combination with inhaled corticosteroid and longacting β2 agonist treatment.

Roflumilast for the treatment of COPD in an Asian population: a randomized, double-blind, parallel-group study.

Background: Roflumilast is the only oral phosphodiesterase 4 inhibitor indicated for use in the treatment of COPD. Previous studies of roflumilast have predominantly involved European and North American populations. A large study was necessary to determine the efficacy and safety of roflumilast in a predominantly ethnic Chinese population.

Pooled subpopulation analyses of the effects of roflumilast on exacerbations and lung function in COPD.

Background: This post-hoc analysis examined the impact of roflumilast on chronic obstructive pulmonary disease (COPD) exacerbations and lung function in patients with COPD who received concomitant long-acting β2-agonists (LABA) with or without prior inhaled corticosteroid (ICS) and the influence of various demographic and clinical characteristics on these outcomes.

Methods: Data were pooled from 2 double-blind, placebo-controlled, 52-week studies of once-daily roflumilast 500 μg in patients with COPD. Endpoints were mean rate of exacerbations and change from baseline in pre- and postbronchodilator FEV1.

Cardiovascular safety in patients receiving roflumilast for the treatment of COPD.

Background: Evaluation of cardiovascular safety for new therapies for COPD is important because of a high prevalence of cardiac comorbidities in the COPD population. Hence, we evaluated the effects of roflumilast, a novel oral phosphodiesterase 4 inhibitor developed for the treatment and prevention of COPD exacerbations, on major adverse cardiovascular events (MACEs).

Methods: Intermediate- and long-term placebo-controlled clinical trials of roflumilast in COPD were pooled and assessed for potential cardiovascular events.

Efficacy of roflumilast in the COPD frequent exacerbator phenotype.

Background: COPD exacerbations are associated with increased morbidity and mortality and can accelerate disease progression. The best predictor of future exacerbations is a history of previous exacerbations, which helps identify a frequent exacerbator phenotype. This post hoc analysis evaluated the effect of roflumilast, a drug known to reduce the COPD exacerbation rate, on exacerbation status.

Does roflumilast decrease exacerbations in severe COPD patients not controlled by inhaled combination therapy? The REACT study protocol.

Background: Many patients with chronic obstructive pulmonary disease (COPD) continue to suffer exacerbations, even when treated with maximum recommended therapy (eg, inhaled combinations of long-acting β2-agonist and high dose inhaled corticosteroids, with or without a long-acting anticholinergic [long-acting muscarinic antagonist]). Roflumilast is approved to treat severe COPD in patients with chronic bronchitis--and a history of frequent exacerbations--as an add-on to bronchodilators.

Purpose: The REACT (Roflumilast in the Prevention of COPD Exacerbations While Taking Appropriate Combination Treatment) study (identification number RO-2455-404-RD, clinicaltrials.

Roflumilast in Asian patients with COPD: A randomized placebo-controlled trial.

Background And Objective: Roflumilast, an oral, selective phosphodiesterase 4 inhibitor, has been shown to reduce exacerbations and improve pulmonary function in patients with COPD. This study examined the efficacy, safety and tolerability of roflumilast in Asian patients with COPD.

Methods: Patients with COPD were randomized 1:1 to enter a 12-week treatment period and receive either oral roflumilast, 500 µg once daily, or placebo, following a single-blind, 4-week baseline period in which all patients received placebo.

Roflumilast in symptomatic chronic obstructive pulmonary disease: two randomised clinical trials.

Background: The phosphodiesterase-4 inhibitor roflumilast can improve lung function and prevent exacerbations in certain patients with chronic obstructive pulmonary disease (COPD). We therefore investigated whether roflumilast would reduce the frequency of exacerbations requiring corticosteroids in patients with COPD.

Methods: In two placebo-controlled, double-blind, multicentre trials (M2-124 and M2-125) with identical design that were done in two different populations in an outpatient setting, patients with COPD older than 40 years, with severe airflow limitation, bronchitic symptoms, and a history of exacerbations were randomly assigned to oral roflumilast (500 microg once per day) or placebo for 52 weeks.

Auto-ADP-ribosylation of Pseudomonas aeruginosa ExoS.

Pseudomonas aeruginosa Exoenzyme S (ExoS) is a bifunctional type-III cytotoxin. The N terminus possesses a Rho GTPase-activating protein (GAP) activity, whereas the C terminus comprises an ADP-ribosyltransferase domain. We investigated whether the ADP-ribosyltransferase activity of ExoS influences its GAP activity.