Heart rate, beta-blocker use, and outcomes of heart failure with reduced ejection fraction.

Aims: High resting heart rate (HR ≥70 b.p.m.) is associated with worse clinical outcomes in heart failure with reduced ejection fraction (HFrEF). Heart rate, guideline-directed medical therapy (GDMT) with beta-blocker (BB), and cardiovascular outcomes were evaluated in a large integrated health network. Methods and results: Using electronic health records we examined patients with chronic HFrEF (ejection fraction ≤35%) in sinus rhythm with at least 1 year of follow-up and available serial HR and medication data between 1 January 2000 and 31 December 2014. Among 6071 patients followed for median of 1330 days across 73 586 total visits, median HR remained stable over time with 61.2% of the follow-up period with HR ≥70 b.p.m. At baseline, 27.9% of patients were on ≥ 50% GDMT target BB dose, 16.2% subjects at baseline, and 19.4% at the end of follow-up had HR ≥70 b.p.m. despite receiving ≥50% of target BB dose. In adjusted analyses, baseline HR was associated with all-cause mortality/heart failure (HF) hospitalization (hazard ratio 1.28 per 15 b.p.m. Heart rate increase; P < 0.001). In comparison, hazard ratio for BB dose was 0.97 (per 77.2 mg increase; P = 0.36). When evaluating patients based on HR and BB dose there was a significant difference in the cumulative hazard for all-cause mortality or HF hospitalization (P < 0.001). For HF hospitalization, hazard appeared to be more closely associated with HR rather than BB dose (P = 0.01). Conclusion: In a real-world analysis, high resting HR was common in HFrEF patients and associated with adverse outcomes. Opportunities exist to improve GDMT and achieve HR control.

Development of Prescription Drug Information Leaflets: Impact of Cognitive Effort and Patient Involvement on Prescription Medication Information Processing.

OBJECTIVE: The objective of this study was to develop a one-page (1-page) prescription drug information leaflet (PILs) and assess their impact on the information processing variables, across 2 levels of patient involvement. METHODS: One-page PILs were developed using cognitive principles to lower mental effort and improve comprehension. An experimental, 3 × 2 repeated measures study was conducted to determine the impact of cognitive effort, manipulated using leaflet type on comprehension across 2 levels (high/low) of patient involvement. Adults (≥18 years) in a university setting in Houston were recruited for the study. Each participant was exposed to 3 different types of prescription drug information leaflet (the current practice, preexisting 1-page text-only, and 1-page PILs) for the 3 drugs (Celebrex, Ventolin HFA, Prezista) for a given involvement scenario. A prevalidated survey instrument was used to measure product knowledge, attitude toward leaflet, and intention to read. RESULTS: Multivariate analysis of variance indicated significant positive effect of cognitive effort, involvement, and their interaction effect across all measured variables. Mean scores for product knowledge, attitude toward leaflet, and intention to read were highest for PILs ( P < .001), indicating that PILs exerted lowest cognitive effort. Univariate and post hoc analysis indicate that product knowledge significantly increases with high involvement. CONCLUSION: Patients reading PILs have higher comprehension compared with the current practice and text-only prototype leaflets evaluated. Higher levels of involvement further improve participant knowledge about the drug, increase their intention to read the leaflet, and change their attitude toward the leaflet. Implementation of PILs would improve information processing for consumers by reducing their cognitive effort.

Role of Information Anxiety and Information Load on Processing of Prescription Drug Information Leaflets.

In this study, we evaluate the role of information anxiety and information load on the intention to read information from prescription drug information leaflets (PILs). These PILs were developed based on the principals of information load and consumer information processing. This was an experimental prospective repeated measures study conducted in the United States where 360 (62% response rate) university students (>18 years old) participated. Participants were presented with a scenario followed by exposure to the three drug product information sources used to operationalize information load. The three sources were: (i) current practice; (ii) pre-existing one-page text only; and (iii) interventional one-page prototype PILs designed for the study. Information anxiety was measured as anxiety experienced by the individual when encountering information. The outcome variable of intention to read PILs was defined as the likelihood that the patient will read the information provided in the leaflets. A survey questionnaire was used to capture the data and the objectives were analyzed by performing a repeated measures MANOVA using SAS version 9.3. When compared to current practice and one-page text only leaflets, one-page PILs had significantly lower scores on information anxiety (p < 0.001) and information load (p < 0.001). The intention to read was highest and significantly different (p < 0.001) for PILs as compared to current practice or text only leaflets. Information anxiety and information load significantly impacted intention to read (p < 0.001). Newly developed PILs increased patient's intention to read and can help in improving the counseling services provided by pharmacists.

Economic burden of hospitalizations of Medicare beneficiaries with heart failure.

OBJECTIVE: The objective of this study was to assess the costs associated with the hospitalization and the cumulative 30-, 60-, and 90-day readmission rates in a cohort of Medicare beneficiaries with heart failure (HF). METHODS: This was a retrospective, observational study based on data from the national 5% sample of Medicare beneficiaries. Inpatient data were gathered for Medicare beneficiaries with at least one HF-related hospitalization between July 1, 2005, and December 31, 2011. The primary end point was the average per-patient cost of hospitalization for individuals with HF. Secondary end points included the cumulative rate of hospitalization, the average length of hospital stay, and the cumulative 30-, 60-, and 90-day readmission rates. RESULTS: Data from 63,678 patients with a mean age of 81.8 years were included in the analysis. All costs were inflated to $2,015 based on the medical care component of the Consumer Price Index. The mean per-patient cost of an HF-related hospitalization was $14,631. The mean per-patient cost of a cardiovascular (CV)-related or all-cause hospitalization was $16,000 and $15,924, respectively. The cumulative rate of all-cause hospitalization was 218.8 admissions per 100 person-years, and the median length of stay for HF-related, CV-related, and all-cause hospitalizations was 5 days. Also, 22.3% of patients were readmitted within 30 days, 33.3% were readmitted within 60 days, and 40.2% were readmitted within 90 days. CONCLUSION: The costs associated with hospitalization for Medicare beneficiaries with HF are substantial and are compounded by a high rate of readmission.

Financial impact of ivabradine on reducing heart failure penalties under the Hospital Readmission Reduction Program.

OBJECTIVE: The introduction of the Hospital Readmission Reduction Program (HRRP) has led to renewed interest in developing strategies to reduce 30 day readmissions among patients with heart failure (HF). In this study, a model was developed to investigate whether the addition of ivabradine to a standard-of-care (SoC) treatment regimen for patients with HF would reduce HRRP penalties incurred by a hypothetical hospital with excess 30 day readmissions. RESEARCH DESIGN: A model using a Monte Carlo simulation framework was developed. Model inputs included national hospital characteristics, hospital-specific characteristics, and the ivabradine treatment effect as quantified by a post hoc analysis of the Systolic Heart failure treatment with the If inhibitor ivabradine Trial (SHIFT). RESULTS: The model computed an 83% reduction in HF readmission penalty payments in a hypothetical hospital with a readmission rate of 22.95% (excess readmission ratio = 1.056 over the national average readmission rate of 21.73%), translating into net savings of $44,016. A sensitivity analysis indicated that the readmission penalty is affected by the specific characteristics of the hospital, including the readmission rate, size of the ivabradine-eligible population, and ivabradine utilization. CONCLUSIONS: The results of this study indicate that the addition of ivabradine to an SoC treatment regimen for patients with HF may lead to a reduction in the penalties incurred by hospitals under the HRRP. This highlights the role ivabradine can play as part of a wider effort to optimize the care of patients with HF.

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.

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

STUDY OBJECTIVE: 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. DESIGN: Retrospective analysis. DATA SOURCE: Electronic health record database that includes clinical, laboratory, and administrative data for all facilities of the University of Utah Health Care System. PATIENTS: 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. MEASUREMENTS AND MAIN RESULTS: The cohort had a mean age of 64 ± 15 years and was predominantly white (71%) and male (74%). Patients received ß-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 ß-blockers, ACEIs, and ARBs at rates of only 24%, 31%, and 13%, respectively. Overall, 58% of patients were prescribed dual therapy with a ß-blocker and an ACEI or ARB, and 19% were prescribed triple therapy (ß-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. CONCLUSION: 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.

Relation of Elevated Heart Rate in Patients With Heart Failure With Reduced Ejection Fraction to One-Year Outcomes and Costs.

There are limited data describing outcomes associated with an elevated heart rate in patients with heart failure with reduced ejection fraction (HFrEF) in routine clinical practice. We identified patients with HFrEF at Duke University Hospital undergoing echocardiograms and heart rate assessments without paced rhythms or atrial fibrillation. Outcomes (all-cause mortality or hospitalization and medical costs per day alive) were assessed using electronic medical records, hospital cost accounting data, and national death records. Patients were stratified by heart rate (<70 and ≥70 beats/min) and compared using generalized linear models specified with gamma error distributions and log links for costs and proportional hazard models for mortality/hospitalization. Of 722 eligible patients, 582 patients (81%) were treated with ß blockers. The median heart rate was 81 beats/min (25th and 75th percentiles 69 to 96) and 527 patients (73%) had a heart rate ≥70 beats/min. After multivariate adjustment, a heart rate ≥70 beats/min was associated with increased 1-year all-cause mortality or hospitalization, hazard ratio 1.37 (95% CI 1.07 to 1.75) and increased medical costs per day alive, cost ratio 2.03 (95% CI 1.53 to 2.69). In conclusion, at a large tertiary care center, despite broad use of ß blockers, a heart rate ≥70 beats/min was observed in 73% of patients with HFrEF and associated with worse 1-year outcomes and increased direct medical costs per day alive.

Expanding Consumer Medication Access: The Time Is Now.

The US FDA is proposing an expanded over-the-counter (OTC) medication policy to improve patient access to medications under the supervision of a pharmacist. Higher levels of medication access via multiple medication categories are common in other industrialized nations. Pharmacists are well trained and widely available. Expanding medication access can help alleviate the physician shortage by directing patients with appropriate health conditions that can be managed with medication to community pharmacists. Examples include migraine headaches and seasonal allergies, which have a significant impact on patients' quality of life and work productivity. Clinically relevant medications and dosages should be selected. Medication use guidelines should not be so restrictive as to defeat the policy intent. The proposed FDA policy is a long-overdue change that will help optimize available health personnel resources for patient care.

An analysis of the warning letters issued by the FDA to pharmaceutical manufacturers regarding misleading health outcomes claims / Análisis de las cartas de advertencia enviadas por la FDA a industrias farmacéuticas sobre propagandas engañosas de resultados en salud

Objective: To evaluate the number and type of warning letters issued by the US Food and Drug Administration (FDA) to pharmaceutical manufacturers for promotional violations. Methods: Two reviewers downloaded, printed and independently evaluated warning letters issued by the FDA to pharmaceutical manufacturers from years 2003-2008. Misleading claims were broadly classified as clinical, Quality-of-Life (QoL), and economic claims. Clinical claims included claims regarding unsubstantiated efficacy, safety and tolerability, superiority, broadening of indication and/or omission of risk information. QoL claims included unsubstantiated quality of life and/or health-related quality of life claims. Economic claims included any form of claim made on behalf of the pharmaceutical companies related to cost superiority of or cost savings from the drug compared to other drugs in the market. Results: In the 6-year study period, 65 warning letters were issued by FDA, which contained 144 clinical, three QoL, and one economic claim. On an average, 11 warning letters were issued per year. Omission of risk information was the most frequently violated claim (30.6%) followed by unsubstantiated efficacy claims (18.6%). Warning letters were primarily directed to manufacturers of cardiovascular (14.6%), anti-microbial (14.6%), and CNS (12.5%) drugs. Majority of the claims referenced in warning letters contained promotional materials directed to physicians (57%). Conclusion: The study found that misleading clinical outcome claims formed the majority of the promotional violations, and majority of the claims were directed to physicians. Since inadequate promotion of medications may lead to irrational prescribing, the study emphasizes the importance of disseminating reliable, credible, and scientific information to patients, and more importantly, physicians to protect public health(AU)

Objetivo: Evaluar el número y el tipo de cartas de advertencia enviadas por la US Food and Drug Admisnitration (FDA) a industrias farmacéuticas por violaciones promocionales. Métodos: Dos revisores descargaron, imprimieron y evaluaron independientemente las cartas de advertencia enviadas por la FDA a industrias farmacéuticas entre os años 2003-2008. Las propagandas engañosas se clasificaron como propagandas clínicas, de calidad de vida (QoL) y económicas. Las propagandas clínicas incluían propagandas de eficacia, seguridad y tolerabilidad, superioridad, amplitud de indicación no sustanciadas, y/u omisión de información de riesgos. Las propagandas de QoL incluían propagandas de calidad de vida o de calidad de vida relacionada con la salud no sustanciadas. Las propagandas económicas incluían cualquier forma de propaganda de las compañías farmacéuticas relacionada con superioridad de costes o ahorro de costes del medicamento comparado con otros en el mercado. Resultados: En los 6 años de estudio, la FDA envió 65 cartas de advertencia que contenían 144 propagandas clínicas, 3 de QoL, y una económica. De media, se enviaron 11 cartas de advertencia por año. La violación más frecuentemente encontrada fue la omisión de la información de riesgo (30,6%), seguida de propagandas de eficacia insustanciadas (18,6%). Las cartas de advertencia fueron dirigidas principalmente a medicamentos cardiovasculares (14,6%), antimicrobianos (14,6%) y del SNC (12,5%). La mayoría de las propagandas referidas en las cartas contenía materiales promocionales dirigidos a los médicos (57%). Conclusión: El estudio encontró que las propagandas engañosas de resultados clínicos consituian la mayoría de las violaciones promocionales, y la mayoría de estas propagandas estaban dirigidas a médicos. Como la promoción inadecuada puede llevar a una prescripción irracional, este estudio enfatiza la importancia de diseminar información fiable, creíble y científica a los pacientes, y más importante a los médicos para así proteger la salud pública(AU)

An analysis of the warning letters issued by the FDA to pharmaceutical manufacturers regarding misleading health outcomes claims.

OBJECTIVE: To evaluate the number and type of warning letters issued by the US Food and Drug Administration (FDA) to pharmaceutical manufacturers for promotional violations. METHODS: Two reviewers downloaded, printed and independently evaluated warning letters issued by the FDA to pharmaceutical manufacturers from years 2003-2008. Misleading claims were broadly classified as clinical, Quality-of-Life (QoL), and economic claims. Clinical claims included claims regarding unsubstantiated efficacy, safety and tolerability, superiority, broadening of indication and/or omission of risk information. QoL claims included unsubstantiated quality of life and/or health-related quality of life claims. Economic claims included any form of claim made on behalf of the pharmaceutical companies related to cost superiority of or cost savings from the drug compared to other drugs in the market. RESULTS: In the 6-year study period, 65 warning letters were issued by FDA, which contained 144 clinical, three QoL, and one economic claim. On an average, 11 warning letters were issued per year. Omission of risk information was the most frequently violated claim (30.6%) followed by unsubstantiated efficacy claims (18.6%). Warning letters were primarily directed to manufacturers of cardiovascular (14.6%), anti-microbial (14.6%), and CNS (12.5%) drugs. Majority of the claims referenced in warning letters contained promotional materials directed to physicians (57%). CONCLUSIONS: The study found that misleading clinical outcome claims formed the majority of the promotional violations, and majority of the claims were directed to physicians. Since inadequate promotion of medications may lead to irrational prescribing, the study emphasizes the importance of disseminating reliable, credible, and scientific information to patients, and more importantly, physicians to protect public health.