Prescribing patterns of evidence-based heart failure pharmacotherapy and outcomes in the ASIAN-HF registry: a cohort study.

Angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs), β blockers, and mineralocorticoid receptor antagonists (MRAs) are of proven benefit and are recommended by guidelines for management of patients with heart failure and reduced ejection fraction (HFrEF). We aimed to examine the first prospective multinational data from Asia on prescribing patterns of guideline-directed medical therapies and analyse its effect on outcomes. In the prospective multinational ASIAN-HF registry (with enrolment from 46 centres in 11 countries in Asia), we enrolled patients aged 18 years or older, with symptomatic heart failure (stage C, with at least one episode of decompensated heart failure in the past 6 months that resulted in admission to hospital or was treated in an outpatient clinic) and left ventricular systolic dysfunction (ejection fraction ≤40% on baseline echocardiography, consistent with 2016 European Society of Cardiology guidelines). We excluded patients with heart failure caused by severe valvular heart disease, life-threatening comorbidity with a life expectancy of less than 1 year, who were unable or unwilling to give consent, or who had concurrent participation in a clinical trial. Patients were followed up for 3 years for the outcomes of death and cause-specific admittance to hospital. Primary outcomes were uptake of guideline-directed medical therapies (as proportions) by therapeutic class, achieved doses as proportions of guideline-recommended doses, and their association with 1-year composite outcome of all-cause death or admittance to hospital because of heart failure. This study is registered with ClinicalTrials.gov, number NCT01633398. Between Oct 1, 2012, and Dec 31, 2015, we enrolled 5276 patients with HFrEF (mean age 59·6 years [SD 13·2], 77% men, body-mass index 24·9 kg/m2 [5·1], 33% New York Heart Association class III or IV). Follow-up data were available for 4544 (90%) of 5061 eligible patients taking medication for heart failure, with median follow-up of 417 days (IQR 214-735). ACE inhibitors or ARBs were prescribed to 3868 (77%) of 5005 patients, β blockers to 3975 (79%) of 5061, and MRAs to 2998 (58%) of 5205, with substantial regional variation. Guideline-recommended dose was achieved in only 17% of cases for ACE inhibitors or ARB, 13% for β blockers, and 29% for MRAs. Country (all three drug classes), increasing body-mass index (ACE inhibitors or ARBs and MRAs), and in-patient recruitment (ACE inhibitors or ARBs and β blockers) were associated with attainment of guideline-recommended dose (all p<0·05). When adjusted for indication bias, increasing drug doses, from low dose (1-<25% of guideline-recommended dose) upwards were associated with lower hazards of a 1-year composite outcome for ACE inhibitors or ARBs and β blockers compared with non-users. The lowest adjusted hazards were in the group that attained guideline-recommended doses above 50% (hazard ratio [HR] 0·54, 95% CI 0·50-0·58 for ACE inhibitors or ARBs [50-99·9%]; HR 0·47, 0·46-0·50 for β blockers, and HR 0·77, 0·72-0·81 for MRAs [≥100%]). Guideline-directed medical therapies at recommended doses are underutilised in patients with HFrEF. Improved uptake and uptitration of guideline-directed medical therapies are needed for better patient outcomes. National Medical Research Council (Singapore), A*STAR Biomedical Research Council ATTRaCT program, Boston Scientific Investigator Sponsored Research program, and Bayer.

Teng TK ，Tromp J ，Tay WT ，Anand I ，Ouwerkerk W ，Chopra V ，Wander GS ，Yap JJ ，MacDonald MR ，Xu CF ，Chia YM ，Shimizu W ，ASIAN-HF investigators ，Richards AM ，Voors A ，Lam CS ... -  《Lancet Global Health》

The treatment gap in patients with chronic systolic heart failure: a systematic review of evidence-based prescribing in practice.

Chin KL ，Skiba M ，Tonkin A ，Reid CM ，Liew D ，Krum H ，Hopper I ... -  《-》

Physicians' guideline adherence is associated with better prognosis in outpatients with heart failure with reduced ejection fraction: the QUALIFY international registry.

To evaluate the impact of physicians' adherence to guideline-recommended medications for heart failure with reduced ejection fraction (HFrEF), including ≥50% prescription of recommended doses, on clinical outcomes at 6-month follow-up. In QUALIFY, an international, prospective, observational, longitudinal survey, 6669 outpatients with HFrEF were recruited 1-15 months after heart failure (HF) hospitalization from September 2013 to December 2014 in 36 countries and followed up at 6 months. A global adherence to guidelines score was developed for prescription of angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), beta-blockers (BBs), mineralocorticoid receptor antagonists (MRAs) and ivabradine and their dosages. Baseline global adherence score was good in 23% of patients, moderate in 55%, and poor in 22%. At 6-month follow-up, poor adherence was associated with significantly higher overall mortality [hazard ratio (HR) 2.21, 95% confidence interval (CI) 1.42-3.44, P=0.001], cardiovascular mortality (HR 2.27, 95% CI 1.36-3.77, P=0.003), HF mortality (HR 2.26, 95% CI 1.21-4.2, P=0.032), combined HF hospitalization or HF death (HR 1.26, 95% CI 1.08-1.71, P=0.024) and cardiovascular hospitalization or cardiovascular death (HR 1.35, 95% CI 1.08-1.69, P=0.013). There was a strong trend between poor adherence and HF hospitalization (HR 1.32, 95% CI 1.04-1.68, P=0.069). Good adherence to pharmacologic treatment guidelines for ACEIs, ARBs, BBs, MRAs and ivabradine, with prescription of at least 50% of recommended dosages, was associated with better clinical outcomes during 6-month follow-up. Continuing global educational initiatives are needed to emphasise the importance of guideline recommendations for optimising drug therapy and prescribing evidence-based doses in clinical practice.

Komajda M ，Cowie MR ，Tavazzi L ，Ponikowski P ，Anker SD ，Filippatos GS ，QUALIFY Investigators ... -  《-》

Identifying optimal doses of heart failure medications in men compared with women: a prospective, observational, cohort study.

Guideline-recommended doses of angiotensin-converting-enzyme (ACE) inhibitors or angiotensin-receptor blockers (ARBs), and β blockers are similar for men and women with heart failure with reduced ejection fraction (HFrEF), even though there are known sex differences in pharmacokinetics of these drugs. We hypothesised that there might be sex differences in the optimal dose of ACE inhibitors or ARBs and β blockers in patients with HFrEF. We did a post-hoc analysis of BIOSTAT-CHF, a prospective study in 11 European countries of patients with heart failure in whom initiation and up-titration of ACE inhibitors or ARBs and β blockers was encouraged by protocol. We included only patients with left ventricular ejection fraction less than 40%, and excluded those who died within the first 3 months. Primary outcome was a composite of time to all-cause mortality or hospitalisation for heart failure. Findings were validated in ASIAN-HF, an independent cohort of 3539 men and 961 women with HFrEF. Among 1308 men and 402 women with HFrEF from BIOSTAT-CHF, women were older (74 [12] years vs 70 [12] years, p<0·0001) and had lower bodyweights (72 [16] kg vs 85 [18] kg, p<0·0001) and heights (162 [7] cm vs 174 [8] cm, p<0·0001) than did men, although body-mass index did not differ significantly. A similar number of men and women reached guideline-recommended target doses of ACE inhibitors or ARBs (99 [25%] vs 304 [23%], p=0·61) and β blockers (57 [14%] vs 168 [13%], p=0·54). In men, the lowest hazards of death or hospitalisation for heart failure occurred at 100% of the recommended dose of ACE inhibitors or ARBs and β blockers, but women showed approximately 30% lower risk at only 50% of the recommended doses, with no further decrease in risk at higher dose levels. These sex differences were still present after adjusting for clinical covariates, including age and body surface area. In the ASIAN-HF registry, similar patterns were observed for both ACE inhibitors or ARBs and β blockers, with women having approximately 30% lower risk at 50% of the recommended doses, with no further benefit at higher dose levels. This study suggests that women with HFrEF might need lower doses of ACE inhibitors or ARBs and β blockers than men, and brings into question what the true optimal medical therapy is for women versus men. European Commission.

Santema BT ，Ouwerkerk W ，Tromp J ，Sama IE ，Ravera A ，Regitz-Zagrosek V ，Hillege H ，Samani NJ ，Zannad F ，Dickstein K ，Lang CC ，Cleland JG ，Ter Maaten JM ，Metra M ，Anker SD ，van der Harst P ，Ng LL ，van der Meer P ，van Veldhuisen DJ ，Meyer S ，Lam CSP ，ASIAN-HF investigators ，Voors AA ... -  《-》

Contemporary Treatment Patterns and Clinical Outcomes of Comorbid Diabetes Mellitus and HFrEF: The CHAMP-HF Registry.

The purpose of this study was to characterize the clinical profile, treatment patterns, and clinical outcomes of patients with comorbid diabetes mellitus (DM) and heart failure with reduced ejection fraction (HFrEF) in a contemporary, real-world U.S. outpatient registry in the context of evolving treatment strategies. Specific antihyperglycemic classes have differential risks and benefits with respect to HF. Limited data are available evaluating contemporary treatment patterns and outcomes of patients with comorbid DM and HFrEF. Among 4,970 patients with chronic HFrEF (≤40%) across 152 U.S. sites in the CHAMP-HF prospective, observational registry (2015 to 2017), we examined therapies and clinical outcomes by DM status. Median age was 68 (58 to 75) years of age; 29% were women; 73.5% were white; and 64% had coronary artery disease. Overall, 42% (n = 2,085) had comorbid DM with a median hemoglobin A1c (HbA1c) level of 7.2% (interquartile range [IQR]: 6.4% to 8.3%). One-fourth of DM patients (24%) were not treated with an antihyperglycemic therapy. Most patients with DM were taking 1 (46%) or 2 (23%) antihyperglycemic therapies: metformin (40%); insulin (33%); sulfonylureas (24%); dipeptidyl peptidase-4 inhibitors (10%); glucagon-like peptide (GLP)-1 receptor agonists (4%); sodium-glucose cotransporter (SGLT)-2 inhibitors (2%); and thiazolidinediones (2%). Among patients with DM, 62%, 16%, 80%, and 33.5% were receiving any angiotensin-converting enzyme (ACE) inhibitor/angiotensin receptor blockers (ARBs), angiotensin receptor-neprilysin inhibitor (ARNI), β-blockers, or mineralocorticoid receptor antagonists (MRAs) at baseline, respectively. Among patients without DM, corresponding baseline rates were 65%, 15%, 80%, and 37%, respectively. Patients with or without DM were infrequently treated with guideline-directed HFrEF therapies at target doses (≤27% across classes). During median 15-month follow-up, patients with DM experienced higher rates of all-cause mortality or HF hospitalization (30% vs. 23%, respectively), independent of 11 pre-specified covariates (adjusted hazard ratio: 1.35 (95% confidence interval: 1.21 to 1.52); p < 0.001). Despite higher risk-adjusted clinical event rates in patients with comorbid HFrEF and DM, guideline-directed medical therapies for both disease states are incomplete and represent an important target for quality improvement through multidisciplinary care pathways.

Vaduganathan M ，Fonarow GC ，Greene SJ ，DeVore AD ，Kavati A ，Sikirica S ，Albert NM ，Duffy CI ，Hill CL ，Patterson JH ，Spertus JA ，Thomas LE ，Williams FB ，Hernandez AF ，Butler J ... -  《-》