Duration of Heightened Risk of Acute Ischemic Stroke After Hospitalization for Acute Systolic Heart Failure.

Background The duration and magnitude of increased stroke risk after a hospitalization for acute systolic heart failure (HF) remains uncertain. Methods and Results The authors performed a retrospective cohort study using claims (2008-2018) from a nationally representative 5% sample of Medicare beneficiaries aged ≥66 years. Cox regression models were fitted separately for the groups with and without acute systolic HF to examine its association with the incidence of ischemic stroke after adjustment for demographics, stroke risk factors, and Charlson comorbidities. Corresponding survival probabilities were used to compute the hazard ratio (HR) in each 30-day interval after discharge. The authors stratified patients by the presence of atrial fibrillation (AF) before or during the hospitalization for acute systolic HF. Among 2 077 501 eligible beneficiaries, 94 641 were hospitalized with acute systolic HF. After adjusting for demographics, stroke risk factors, and Charlson comorbidities, the risk of ischemic stroke was highest in the first 30 days after discharge from an acute systolic HF hospitalization for patients with AF (HR, 2.4 [95% CI, 2.1-2.7]) and without AF (HR, 4.6 [95% CI, 4.0-5.3]). The risk of stroke remained elevated for 60 days in patients with AF (HR, 1.4 [95% CI, 1.2-1.6]) and was not significantly elevated afterward. The risk of stroke remained significantly elevated through 330 days in patients without AF (HR, 2.1 [95% CI, 1.7-2.7]) and was no longer significantly elevated afterward. Conclusions A hospitalization for acute systolic HF is associated with an increased risk of ischemic stroke up to 330 days in patients without concomitant AF.

Effectiveness of angiotensin-neprilysin inhibitor treatment versus renin-angiotensin system blockade in older adults with heart failure in clinical care.

OBJECTIVE: To evaluate the effectiveness of angiotensin receptor-neprilysin inhibitor (ARNI) versus renin-angiotensin system (RAS) blockade alone in older adults with heart failure with reduced ejection fraction (HFrEF). METHODS: We conducted a cohort study using US Medicare fee-for-service claims data (2014-2017). Patients with HFrEF ≥65 years were identified in two cohorts: (1) initiators of ARNI or RAS blockade alone (ACE inhibitor, ACEI; or angiotensin receptor blocker, ARB) and (2) switchers from an ACEI to either ARNI or ARB. HR with 95% CI from Cox proportional hazard regression and 1-year restricted mean survival time (RMST) difference with 95% CI were calculated for a composite outcome of time to first worsening heart failure event or all-cause mortality after adjustment for 71 pre-exposure characteristics through propensity score fine-stratification weighting. All analyses of initiator and switcher cohorts were conducted separately and then combined using fixed effects. RESULTS: 51 208 patients with a mean age of 76 years were included, with 16 193 in the ARNI group. Adjusted HRs comparing ARNI with RAS blockade alone were 0.92 (95% CI 0.84 to 1.00) among initiators and 0.79 (95% CI 0.74 to 0.85) among switchers, with a combined estimate of 0.84 (95% CI 0.80 to 0.89). Adjusted 1-year RMST difference (95% CI) was 4 days in the initiator cohort (-1 to 9) and 12 days (8 to 17) in the switcher cohort, resulting in a pooled estimate of 9 days (6 to 12) favouring ARNI. CONCLUSION: ARNI treatment was associated with lower risk of a composite effectiveness endpoint compared with RAS blockade alone in older adults with HFrEF.

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% of which is directly attributable to hospitalizations. The SHIFT clinical study demonstrated that ivabradine plus standard of care (SoC) reduced HF-related and all-cause hospitalizations compared with SoC alone. 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%, increasing 2% per year. 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. DISCLOSURES: This study was funded by Amgen. Patel is employed by Amgen; Kielhorn was employed by Amgen at the time of the study but is no longer affiliated with Amgen. Borer, Böhm, Ford, and Komajda have received scientific support, consultative fees, and/or speakers honoraria from Servier and Amgen in connection with SHIFT, the trial underlying this analysis. Borer also has received consultative fees from Celladon, Pfizer, ARMGO, Cardiorentis, Novartis, and Takeda USA. Kansal, Dorman, Krotneva, and Zheng are employees of Evidera, which was hired to assist with this study. Tavazzi has received research grants and consultation fees from Servier in connection with this study and has had advisory board memberships with Boston Scientific, Servier, Cardiorentis, Medtronic, St. Jude Medical, and CVie Therapeutics. Study concept and design were contributed by Dorman and Keilhorn, along with the other authors. Tavazzi, Komajda, Ford, BÖhm, and Borer oversaw collection of the data. Tavazzi, Komajda, Ford, BÖhm, and Borer (along with Karl Swedberg) formed the Executive Committee of SHIFT, the trial underlying this analysis. The manuscript was written by Kansal, along with the other authors, and revised by Borer and Patel, with assistance from the other authors.

Resource use and cost implications of implementing a heart failure program for patients with systolic heart failure in Swedish primary health care.

AIM: Heart failure (HF) is a common but serious condition which involves a significant economic burden on the health care economy. The purpose of this study was to evaluate cost and quality of life (QoL) implications of implementing a HF management program (HFMP) in primary health care (PHC). METHODS AND RESULTS: This was a prospective randomized open-label study including 160 patients with a diagnosis of HF from five PHC centers in south-eastern Sweden. Patients randomized to the intervention group received information about HF from HF nurses and from a validated computer-based awareness program. HF nurses and physicians followed the patients intensely in order to optimize HF treatment according to current guidelines. The patients in the control group were followed by their regular general practitioner (GP) and received standard treatment according to local management routines. No significant changes were observed in NYHA class and quality-adjusted life years (QALY), implying that functional class and QoL were preserved. However, costs for hospital care (HC) and PHC were reduced by EUR 2167, or 33%. The total cost was EUR 4471 in the intervention group and EUR 6638 in the control group. CONCLUSIONS: Introducing HFMP in Swedish PHC in patients with HF entails a significant reduction in resource utilization and costs, and maintains QoL. Based on these results, a broader implementation of HFMP in PHC may be recommended. However, results should be confirmed with extended follow-up to verify long-term effects.

Digoxin use and lower 30-day all-cause readmission for Medicare beneficiaries hospitalized for heart failure.

BACKGROUND: Heart failure is the leading cause for hospital readmission, the reduction of which is a priority under the Affordable Care Act. Digoxin reduces 30-day all-cause hospital admission in chronic systolic heart failure. Whether digoxin is effective in reducing readmission after hospitalization for acute decompensation remains unknown. METHODS: Of the 5153 Medicare beneficiaries hospitalized for acute heart failure and not receiving digoxin, 1054 (20%) received new discharge prescriptions for digoxin. Propensity scores for digoxin use, estimated for each of the 5153 patients, were used to assemble a matched cohort of 1842 (921 pairs) patients (mean age, 76 years; 56% women; 25% African American) receiving and not receiving digoxin, who were balanced on 55 baseline characteristics. RESULTS: Thirty-day all-cause readmission occurred in 17% and 22% of matched patients receiving and not receiving digoxin, respectively (hazard ratio [HR] for digoxin, 0.77; 95% confidence interval [CI], 0.63-0.95). This beneficial association was observed only in those with ejection fraction <45% (HR 0.63; 95% CI, 0.47-0.83), but not in those with ejection fraction ≥ 45% (HR 0.91; 95% CI, 0.60-1.37; P for interaction, .145), a difference that persisted throughout the first 12 months postdischarge (P for interaction, .019). HRs (95% CIs) for 12-month heart failure readmission and all-cause mortality were 0.72 (0.61-0.86) and 0.83 (0.70-0.98), respectively. CONCLUSIONS: In Medicare beneficiaries with systolic heart failure, a discharge prescription of digoxin was associated with lower 30-day all-cause hospital readmission, which was maintained at 12 months, and was not at the expense of higher mortality. Future randomized controlled trials are needed to confirm these findings.

Effectiveness and safety of digoxin among contemporary adults with incident systolic heart failure.

BACKGROUND: Clinical guidelines recommend digoxin for patients with symptomatic systolic heart failure (HF) receiving optimal medical therapy, but this recommendation is based on limited, older trial data. We evaluated the effectiveness and safety of digoxin in a contemporary cohort of patients with incident systolic HF. METHODS AND RESULTS: We identified adults with incident systolic HF between 2006 and 2008 within Kaiser Permanente Northern California who had no prior digoxin use. We used multivariable extended Cox regression to examine the association between new digoxin use and risks of death and HF hospitalization, controlling for medical history, laboratory results, medications, HF disease severity, and the propensity for digoxin use. We also conducted analyses stratified by sex and concurrent ß-blocker use. Among 2891 newly diagnosed patients with systolic HF, 529 (18%) received digoxin. During a median 2.5 years of follow-up, incident digoxin use was associated with higher rates of death (14.2 versus 11.3 per 100 person-years) and HF hospitalization (28.2 versus 24.4 per 100 person-years). In multivariable analysis, incident digoxin use was associated with higher mortality (hazard ratio, 1.72; 95% confidence interval, 1.25-2.36) but no significant difference in the risk of HF hospitalization (hazard ratio, 1.05; 95% confidence interval, 0.82-1.34). Results were similar in analyses stratified by sex and ß-blocker use. CONCLUSIONS: Digoxin use in patients with incident systolic HF was independently associated with a higher risk of death but no difference in HF hospitalization.

The inpatient experience and predictors of length of stay for patients hospitalized with systolic heart failure: comparison by commercial, Medicaid, and Medicare payer type.

OBJECTIVE: Descriptions of the inpatient experience for patients hospitalized with systolic heart failure (HF) are limited and lack a cross-sectional representation of the US population. While length of stay (LOS) is a primary determinant of resource use and post-discharge events, few models exist for estimating LOS. RESEARCH DESIGN AND METHODS: MarketScan(®) administrative claims data from 1/1/2005-6/30/2008 were used to select hospitalized patients aged ≥18 years with discharge diagnoses for both HF (primary diagnosis) and systolic HF (any diagnostic position) without prior HF hospitalization or undergoing transplantation. RESULTS: Among 17,597 patients with systolic HF; 4109 had commercial; 2118 had Medicaid; and 11,370 had Medicare payer type. Medicaid patients had longer mean LOS (7.1 days) than commercial (6.3 days) or Medicare (6.7 days). In-hospital mortality was highest for patients with Medicaid (2.4%), followed by Medicare (1.3%) and commercial (0.6%). Commercial patients were more likely to receive inpatient procedures. Renal failure, pressure ulcer, malnutrition, a non-circulatory index admission DRG, receipt of a coronary artery bypass procedure or cardiac catheterization, or need for mechanical ventilation during the index admission were associated with increased LOS; receipt of a pacemaker device at index was associated with shorter LOS. LIMITATIONS: Selection of patients with systolic HF is limited by completeness and accuracy of medical coding, and results may not be generalizable to patients with diastolic HF or to international populations. CONCLUSION: Inpatient care, LOS, and in-hospital survival differ by payer among patients hospitalized with systolic HF, although co-morbidity and inpatient procedures consistently influence LOS across payer types. These findings may refine risk stratification, allowing for targeted intensive inpatient management and/or aggressive transitional care to improve outcomes and increase the efficiency of care.

Mode of action and effects of standardized collaborative disease management on mortality and morbidity in patients with systolic heart failure: the Interdisciplinary Network for Heart Failure (INH) study.

BACKGROUND: Trials investigating efficacy of disease management programs (DMP) in heart failure reported contradictory results. Features rendering specific interventions successful are often ill defined. We evaluated the mode of action and effects of a nurse-coordinated DMP (HeartNetCare-HF, HNC). METHODS AND RESULTS: Patients hospitalized for systolic heart failure were randomly assigned to HNC or usual care (UC). Besides telephone-based monitoring and education, HNC addressed individual problems raised by patients, pursued networking of health care providers and provided training for caregivers. End points were time to death or rehospitalization (combined primary), heart failure symptoms, and quality of life (SF-36). Of 1007 consecutive patients, 715 were randomly assigned (HNC: n=352; UC: n=363; age, 69±12 years; 29% female; 40% New York Heart Association class III-IV). Within 180 days, 130 HNC and 137 UC patients reached the primary end point (hazard ratio, 1.02; 95% confidence interval, 0.81-1.30; P=0.89), since more HNC patients were readmitted. Overall, 32 HNC and 52 UC patients died (1 UC patient and 4 HNC patients after dropout); thus, uncensored hazard ratio was 0.62 (0.40-0.96; P=0.03). HNC patients improved more regarding New York Heart Association class (P=0.05), physical functioning (P=0.03), and physical health component (P=0.03). Except for HNC, health care utilization was comparable between groups. However, HNC patients requested counseling for noncardiac problems even more frequently than for cardiovascular or heart-failure-related issues. CONCLUSIONS: The primary end point of this study was neutral. However, mortality risk and surrogates of well-being improved significantly. Quantitative assessment of patient requirements suggested that besides (tele)monitoring individualized care considering also noncardiac problems should be integrated in efforts to achieve more sustainable improvement in heart failure outcomes. CLINICAL TRIAL REGISTRATION: URL: http://www.controlled-trials.com. Unique identifier: ISRCTN23325295.