Pharmacotherapy Treatment Patterns, Outcomes, and Health Resource Utilization Among Patients with Heart Failure with Reduced Ejection Fraction at a U.S. Academic Medical Center.

To assess clinical characteristics, pharmacotherapy treatment patterns, resource utilization and associated charges, and morbidity and mortality outcomes among a real-world cohort of patients with heart failure with reduced ejection fraction (HFrEF) in an academic medical center setting. Retrospective analysis. Electronic health record database that includes clinical, laboratory, and administrative data for all facilities of the University of Utah Health Care System. A total of 989 adults with prevalent (preexisting) HFrEF, identified by using the International Classification of Diseases, Ninth Revision, Clinical Modification code 428.x (heart failure) between January 1, 2007, and June 30, 2013, and who had a left ventricular ejection fraction of 40% or lower. The cohort had a mean age of 64 ± 15 years and was predominantly white (71%) and male (74%). Patients received β-blockers, angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs), and aldosterone receptor antagonists (ARAs) at rates of 79%, 69%, and 29%, respectively. Patients achieved target doses of β-blockers, ACEIs, and ARBs at rates of only 24%, 31%, and 13%, respectively. Overall, 58% of patients were prescribed dual therapy with a β-blocker and an ACEI or ARB, and 19% were prescribed triple therapy (β-blocker, an ACEI or ARB, and an ARA). Univariate and multivariate logistic regression models were used to assess the association between baseline characteristics with the presence of triple therapy. Two variables were statistically significant in both models: increasing age was associated with a lower odds of triple therapy (univariate: odds ratio [OR] 0.760, 95% confidence interval [CI] 0.673-0.857; multivariate: OR 0.768, 95% CI 0.625-0.942), whereas receipt of an implantable cardiac device was associated with a 2-fold increase in the odds of triple therapy (univariate: OR 2.1, 95% CI 1.4-3.1; multivariate: OR 2.1, 95% CI 1.3-3.5). During a mean ± SD follow-up of 36 ± 27 months, all-cause mortality was 0.12 per person-year. There were 1311 all-cause hospitalizations of which 611 (47%) were for worsening heart failure. The rate of all-cause and heart failure-specific hospitalizations was 0.44 and 0.21 per person-year of follow-up, respectively. The median length of stay was 6.4 ± 8.8 days, and the median charge was $22,310. The 30-day all-cause readmission rate was 20%, and the primary reason for readmission was heart failure in 65% of cases. This study demonstrates the continuing significant disease and economic burden for patients with HFrEF. Challenges remain in utilization of established disease-modifying therapy and in the treatment of patients with HFrEF and multiple comorbidities.

Bress AP ，King JB ，Brixner D ，Kielhorn A ，Patel HK ，Maya J ，Lee VC ，Biskupiak J ，Munger M ... -  《-》

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》

Beta-blockers and inhibitors of the renin-angiotensin aldosterone system for chronic heart failure with preserved ejection fraction.

Martin N ，Manoharan K ，Davies C ，Lumbers RT ... -  《Cochrane Database of Systematic Reviews》

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 ... -  《-》

Variation in use and dosing escalation of renin angiotensin system, mineralocorticoid receptor antagonist, angiotensin receptor neprilysin inhibitor and beta-blocker therapies in heart failure and reduced ejection fraction: Association of comorbidities.

In patients with heart failure and reduced ejection fraction (HFrEF), angiotensin converting enzyme inhibitors (ACEi), angiotensin II receptor blockers (ARB), or angiotensin receptor neprilysin inhibitor (ARNI), mineralocorticoid receptor antagonists (MRA), and beta-blockers (βB) are underutilized. It is unknown if patients with and without comorbidities have similar ACEi/ARB/ARNI, MRA, and βB prescription patterns. Baseline data from the CHAMP-HF (Change the Management of Patients with Heart Failure) registry were categorized by history of atrial fibrillation, asthma/chronic lung disease, obstructive sleep apnea, and depression. Using multivariate hierarchical logistic models, associations of ACEi/ARB/ARNI, MRA and βB medication use and dose by comorbidities were assessed after adjusting for patient characteristics. Of 4,815 HFrEF patients from 152 CHAMP-HF sites, ACEi/ARB/ARNI use was lower in patients with more comorbidities, and generally, MRA use was low and βB use was high. In adjusted analyses, patients with HFrEF and comorbid obstructive sleep apnea, vs. without, were more likely to be prescribed ARNI (OR [95% CI]: 1.25 [1.00, 1.55]); P = .047 and MRA (1.31 [1.11, 1.55]); P = .002 and less likely to be prescribed ACEi (0.74 [0.63, 0.88]); P < .001. Patients with atrial fibrillation, vs. without, were less likely to receive ACEi/ARB (0.82 [0.71, 0.95]); P = .006 and any study medication (0.81 [0.67, 0.97]); P = .020. Comorbid lung disease and history of depression were not associated with HFrEF prescriptions. Renin-angiotensin-aldosterone blockade therapy prescription and dose varied by comorbidity status, but βB therapy did not. In quality efforts, leaders need to consider use and dosing of prescriptions in light of prevalent comorbidities.

Albert NM ，Tyson RJ ，Hill CL ，DeVore AD ，Spertus JA ，Duffy C ，Butler J ，Patterson JH ，Hernandez AF ，Williams FB ，Thomas L ，Fonarow GC ... -  《-》