Top ten risk factors for morbidity and mortality in patients with chronic systolic heart failure and elevated heart rate: the SHIFT risk model

Aims We identified easily obtained baseline characteristics associated with outcomes in patients with chronic heart failure (HF) and elevated heart rate (HR) receiving contemporary guideline-recommended therapy in the SHIFT trial, and used them to develop a prognostic model. Methods We selected the 10 best predictors for each of four outcomes (cardiovascular death or HF hospitalisation; all-cause mortality; cardiovascular mortality; and HF hospitalisation). All variables with p &#60; 0.05 for association were entered into a forward stepwise Cox regression model. Our initial analysis excluded baseline therapies, though randomisation to ivabradine or placebo was forced into the model for the composite endpoint and HF hospitalisation. Results Increased resting HR, low ejection fraction, raised creatinine, New York Heart Association class III/IV, longer duration of HF, history of left bundle branch block, low systolic blood pressure and, for three models, age were strong predictors of all outcomes. Additional predictors were low body mass index, male gender, ischaemic HF, low total cholesterol, no history of hyperlipidaemia or dyslipidaemia and presence of atrial fibrillation/flutter. The c-statistics for the four outcomes ranged from 67.6% to 69.5%. There was no evidence for lack of fit of the models with the exception of all-cause mortality (p = 0.017). Similar results were found including baseline therapies. Conclusion The SHIFT Risk Model includes simple, readily obtainable clinical characteristics to produce important prognostic information in patients with chronic HF, systolic dysfunction, and elevated HR. This may help better calibrate management to individual patient risk.</p

Efficacy profile of ivabradine in patients with heart failure plus angina pectoris

Objectives: In the Systolic Heart Failure Treatment with the If Inhibitor Ivabradine Trial (SHIFT), slowing of the heart rate with ivabradine reduced cardiovascular death or heart failure hospitalizations among patients with systolic chronic heart failure (CHF). Subsequently, in the Study Assessing the Morbidity-Mortality Benefits of the If Inhibitor Ivabradine in Patients with Coronary Artery Disease (SIGNIFY) slowing of the heart rate in patients without CHF provided no benefit for cardiovascular death or nonfatal myocardial infarction (primary composite end point), with secondary analyses suggesting possible harm in the angina subgroup. Therefore, we examined the impact of ivabradine in the patients with CHF plus angina in SHIFT. Methods: SHIFT enrolled adults with stable, symptomatic CHF, a left ventricular ejection fraction ≤35% and a sinus rhythm with a resting heart rate ≥70 bpm. Outcomes were the SHIFT and SIGNIFY primary composite end points and their components. Results: Of 6,505 patients in SHIFT, 2,220 (34%) reported angina at randomization. Ivabradine numerically, but not significantly, reduced the SIGNIFY primary composite end point by 8, 11 and 11% in the SHIFT angina subgroup, nonangina subgroup and overall population, respectively. Ivabradine also reduced the SHIFT primary composite end point in all 3 subgroups. Conclusions: In SHIFT, ivabradine showed consistent reduction of cardiovascular outcomes in patients with CHF; similar results were seen in the subgroup of SHIFT patients with angina

Respiratory management in severe acute respiratory syndrome coronavirus 2 infection.

The severe acute respiratory syndrome coronavirus 2 pandemic is to date affecting more than a million of patients and is challenging healthcare professionals around the world. Coronavirus disease 2019 may present with a wide range of clinical spectrum and severity, including severe interstitial pneumonia with high prevalence of hypoxic respiratory failure requiring intensive care admission. There has been increasing sharing experience regarding the patient's clinical features over the last weeks which has underlined the need for general guidance on treatment strategies. We summarise the evidence existing in the literature of oxygen and positive pressure treatments in patients at different stages of respiratory failure and over the course of the disease, including environment and ethical issues related to the ongoing coronavirus disease 2019 infection

Budget impact of adding ivabradine to standard of care in patients with chronic systolic heart failure in the United States

BACKGROUND: Heart failure (HF) costs $21 billion annually in direct health care costs, 80 OBJECTIVE: To estimate the budget impact of ivabradine from a U.S. commercial payer perspective. METHODS: A budget impact model estimated the per-member-per month (PMPM) impact of introducing ivabradine to existing formularies by comparing a reference scenario (SoC) and a new drug scenario (ivabradine + SoC) in hypothetical 1 million-member commercial and Medicare Advantage plans. In both scenarios, U.S. claims data were used for the reference cumulative annual rates of hospitalizations (HF, non-HF cardiovascular [CV], and non-CV), and hospitalization rates were adjusted using SHIFT data. The model controlled for mortality risk using SHIFT and U.S. life table data, and hospitalization costs were obtained from U.S. claims data: HF-related =$37,507; non-HF CV = $28,951; and non-CV =$17,904. The annualized wholesale acquisition cost of ivabradine was $4,500, with baseline use for this new drug at 2 RESULTS: Based on the approved U.S. indication, approximately 2,000 commercially insured patients from a 1 million-member commercial plan were eligible to receive ivabradine. Ivabradine resulted in a PMPM cost savings of$0.01 and $0.04 in years 1 and 3 of the core model, respectively. After including the acquisition price for ivabradine, the model showed a decrease in total costs in the commercial ($991,256 and $474,499, respectively) and Medicare populations ($13,849,262 and $4,280,291, respectively) in year 1. This decrease was driven by ivabradine’s reduction in hospitalization rates. For the core model, the estimated pharmacy-only PMPM in year 1 was$0.01 for the commercial population and $0.24 for the Medicare Advantage population. CONCLUSIONS: Adding ivabradine to SoC led to lower average annual treatment costs. The negative PMPM budget impact indicates that ivabradine is an affordable option for U.S. payers

Incremental benefit of drug therapies for chronic heart failure with reduced ejection fraction: a network meta-analysis

Aims: A network meta‐analysis (NMA) of all recommended drug groups for the treatment of heart failure with reduced ejection fraction (HFrEF), including their combinations, was performed to assess the relative efficacy and incremental benefit. Methods and results: A search was made in biomedical databases for randomized controlled trials published between 1987 and 2017 on angiotensin‐converting enzyme inhibitors (ACEIs), beta‐blockers (BBs), angiotensin receptor blockers (ARBs), mineralocorticoid receptor antagonists (MRAs), ivabradine (IVA), or angiotensin receptor–neprilysin inhibitors (ARNI). A total of 58 relevant trials were identified. The relative efficacy of each treatment group (or combination) in terms of all‐cause mortality, cardiovascular mortality, all‐cause hospitalizations and hospitalizations for heart failure, per patient‐year of follow‐up, were combined in a random‐effects Bayesian NMA. The pairwise comparison between each regimen and for each outcome was estimated. The NMA was dominated by 15 large‐scale trials with between 1984 and 18 898 patient‐years of follow‐up. Combinations of drug groups showed incremental benefits on outcomes over single groups. The most effective combinations were ARNI+BB + MRA and ACEI+BB + MRA + IVA, showing reductions in all‐cause mortality (vs. placebo) of 62% and 59%, respectively; hazard ratios were 0.38 [credible interval (CrI) 0.20–0.65] and 0.41 (CrI 0.21–0.70); and in all‐cause hospitalizations with reductions of 42% for both. These two combinations were also the most effective for the other outcomes studied. Conclusion: Our analysis shows that the incremental use of combinations of disease‐modifying therapies has resulted in the progressive improvement in mortality and hospitalization outcomes in HFrEF. Our findings support the current guideline recommendations

Does blue-violet filtering in contact or ophthalmic lenses improve contrast sensitivity?

he effects of blue-violet filtering lenses (yellow lenses) on visual performances and more specifically on contrast sensitivity (CS) are still debated in the literature. In this work, results obtained with contact lenses (CLs) and oph- thalmic lenses (OphLs) with different optical properties are compared and discussed. A negative statistically significant (p < 0.05) moderate correlation of the CS varia- tion with different lenses as a function of the CS of the subject with the clearer one was observed. This means that filtering is expected to produce a CS worsening in subjects showing a relatively high initial CS. On the contrary, subjects showing a relatively low initial CS are expected to show a CS improvement

Reduction In body weight is an independent risk factor for mortality in chronic heart failure. Insights from GISSI-HF and Val-HeFT trials

n/

Decrease in n-acetylaspartate following concussion may be coupled to decrease in creatine

Objectives: To assess the time course changes in brain N-acetylaspartate (NAA) and creatine (Cr) in athletes who suffered a sport-related concussion. Participants: Eleven non-consecutive concussed athletes and 11 sex and age-matched control volunteers. Main outcome measures: At 3, 15, 30 and 45 days post-injury, athletes were examined by proton Magnetic Resonance Spectroscopy (1H-MRS) for the determination of NAA,(Cr) and choline (Cho). 1H-MRS data recorded in the control group were used for comparison. Results: Compared to controls (2.18 ± 0.19), athletes showed an NAA/Cr increase at 3 (2.71 ± 0.16; p < 0.01) and 15 days (2.54 ± 0.21; p < 0.01), followed by a decrease and subsequent normalization at 30 (1.95 ± 0.16, p < 0.05) and 45 days(2.17 ± 0.20; p <0.05) post-concussion. NAA/Cho decreased at 3, 15 and 30 days post-injury (p < 0.01 compared to controls), with no differences from controls at 45 days post-concussion. Significant increase in the Cho/Cr after 3 (+33%, p < 0.01) and 15 (+31.5%, p < 0.01) days post-injury was observed, whilst no differences compared to controls were recorded at 30 and 45 days post-impact. Conclusions: This cohort of athletes indicates that concussion may cause concomitant decrease in cerebral NAA and Cr. This occurrence provokes longer time of metabolism normalization, as well as longer resolution time of concussion-associated clinical symptoms

Patient factors associated with titration of medical therapy in patients with heart failure with reduced ejection fraction: data from the QUALIFY international registry

Aims: Failure to prescribe key medicines at evidence-based doses is associated with increased mortality and hospitalization forpatients with Heart Failure with reduced Ejection Fraction (HFrEF). We assessed titration patterns of guideline-recommendedHFrEF medicines internationally and explored associations with patient characteristics in the global, prospective, observational,longitudinal registry. Methods and results: Data were collected from September 2013 through December 2014, with 7095 patients from 36 coun-tries [>18 years, previous HF hospitalization within 1–15 months, left ventricular ejection fraction (LVEF)≤40%] enrolled, withdosage data at baseline and up to 18 months from 4368 patients. In 4368 patients (mean age 63 ± 17 years, 75% male)≥100%target doses at baseline: 30.6% (ACEIs), 2.9% (ARBs), 13.9% (BBs), 53.8% (MRAs), 26.2% (ivabradine). Atfinal follow-up,≥100%target doses achieved in more patients for ACEI (34.8%), BB (18.0%), and ivabradine (30.5%) but unchanged for ARBs (3.2%)and MRAs (53.7%). Adjusting for baseline dosage, uptitration during follow-up was more likely with younger age, highersystolic blood pressure, and in absence of chronic kidney disease or diabetes for ACEIs/ARBs; younger age, higher body massindex, higher heart rate, lower LVEF, and absence of coronary artery disease for BBs. For ivabradine, uptitration was morelikely with higher resting heart rate. Conclusions: The international QUALIFY Registry suggests that few patients with HFrEF achieve target doses ofdisease-modifying medication, especially older patients and those with co-morbidity. Quality improvement initiatives are ur-gently required

Beneficial effects of ivabradine in patients with heart failure, low ejection fraction, and heart rate above 77 b.p.m.

Aims: Ivabradine has been approved in heart failure with reduced ejection fraction (HFrEF) and elevated heart rate despite guideline‐directed medical therapy (GDMT) to reduce cardiovascular (CV) death and hospitalization for worsening HF. The median value of 77 b.p.m. is the lower bound selected for the regulatory approval in Canada, South Africa, and Australia. Patient‐reported outcomes (PROs) including symptoms, quality of life, and global assessment are considered of major interest in the global plan of care of patients with HF. However, the specific impact of GDMT, and specifically ivabradine, on PRO remains poorly studied. In the subgroup of patients from the Systolic Heart failure treatment with the If inhibitor ivabradine Trial (SHIFT) who had heart rate above the median of 77 b.p.m. (pre‐specified analysis) and for whom the potential for improvement was expected to be larger, we aimed (i) to evaluate the effects of ivabradine on PRO (symptoms, quality of life, and global assessment); (ii) to consolidate the effects of ivabradine on the primary composite endpoint of CV death and hospitalization for HF; and (iii) to reassess the effects of ivabradine on left ventricular (LV) remodelling. Methods and results: Comparisons were made according to therapy, and proportional hazards models (adjusted for baseline beta‐blocker therapy) were used to estimate the association between ivabradine and various outcomes. In SHIFT, n = 3357 (51.6%) patients had a baseline heart rate &gt; 77 b.p.m. After a median follow‐up of 22.9 months (inter‐quartile range 18–28 months), ivabradine on top of GDMT improved symptoms (28% vs. 23% improvement in New York Heart Association functional class, P = 0.0003), quality of life (5.3 vs. 2.2 improvement in Kansas City Cardiomyopathy Questionnaire overall summary score, P = 0.005), and global assessment [from both patient (improved in 72.3%) and physician (improved in 61.0%) perspectives] significantly more than did placebo (both P &lt; 0.0001). Ivabradine induced a 25% reduction in the combined endpoint of CV death and hospitalization for HF (hazard ratio 0.75; P &lt; 0.0001), which translates into a number of patients needed to be treated for 1 year of 17. Patients under ivabradine treatment demonstrated a significant reduction in LV dimensions when reassessed at 8 months (P &lt; 0.05). Conclusions: In patients with chronic HFrEF, sinus rhythm, and a heart rate &gt; 77 b.p.m. while on GDMT, the present analysis brings novel insights into the role of ivabradine in improving the management of HFrEF, particularly with regard to PRO (ISRCTN70429960)