Cost-effectiveness of systematic screening and treatment of transthyretin amyloid cardiomyopathy (ATTR-CM) in patients with heart failure with preserved ejection fraction (HFpEF) in United States.

BACKGROUND: Transthyretin amyloid cardiomyopathy (ATTR-CM) is an underdiagnosed cause of heart failure in clinical practice. 99mTc-pyrophosphate scintigraphy (PYP-scan) improves the accuracy of ATTR-CM detection, enabling timely initiation of tafamidis, a drug that slows the progression of ATTR-CM and lowers the risk of adverse cardiac events. PYP-scans, serum free light-chain (FLC) test and immunofixation electrophoresis (IFE) are critical components of a systematic screening. We assessed the cost-effectiveness of universal systematic screening (USS) compared to standard-of-care (SoC) selected clinical referrals for the systematic screening in patients aged 60 years or older with heart failure with preserved ejection fraction (HFpEF) and ventricular wall thickness of at least 12 mm. METHODS: Two screening strategies, USS versus SoC screening for ATTR-CM were compared in a model-based assessment. Treatment decisions were based upon the accuracy of each screening strategy, which was followed by Markov state transitions across New York Heart Association (NYHA) functional classes and death. Model inputs were identified from a literature review. We calculated lifetime cost in 2022 US dollars and quality adjusted life-years (QALYs) of each strategy. The primary outcome was the incremental cost-effectiveness ratio (ICER). RESULTS: The USS was associated with a significant increase in lifetime costs ($124,380 vs. $70,412) and modest improvement in QALYs (4.42 QALYs vs 4.36 QALYs). The ICER for the USS was $919,509 per QALY gained. ICER was sensitive to the age at the time of ATTR-CM diagnosis, true prevalence rate of ATTR-CM, and daily cost of tafamidis. CONCLUSIONS: Owing to the high cost of treatment with tafamidis, USS along with PYP scan for ATTR-CM in older HFpEF patients with ventricular wall thickening is unlikely to become a cost-effective strategy at a liberal WTP threshold.

Cost-Effectiveness of Strategies to Personalize the Selection of P2Y12 Inhibitors in Patients with Acute Coronary Syndrome.

PURPOSE: Perform a cost-effectiveness analysis comparing strategies for selecting P2Y12 inhibitors in acute coronary syndrome (ACS). METHODS: Six strategies for selection of P2Y12 inhibitors in ACS were compared from the US healthcare system perspective: (1) clopidogrel for all (universal clopidogrel); (2) ticagrelor guided by platelet reactivity assay (PRA; clopidogrel + phenotype); (3) ticagrelor use only in CYP2C19 poor metabolizers (genotype + conservative ticagrelor); (4) ticagrelor use in both CYP2C19 intermediate and poor metabolizers (genotype + liberal ticagrelor); (5) ticagrelor use only in patients with CYP2C19 polymorphisms and clopidogrel nonresponse by PRA (genotype + phenotype); and (6) ticagrelor for all (universal ticagrelor). A decision model was developed to model major adverse cardiovascular events and bleeding during 1 year of treatment with a P2Y12 inhibitor. Model inputs were identified from the literature. Lifetime costs were adjusted to 2017 US dollars; quality-adjusted life-years (QALYs) were projected using a Markov model. The primary endpoint was the incremental cost-effectiveness compared to the next best option along the cost-effectiveness continuum. Sensitivity analyses were performed on all model inputs to assess their influence on the incremental cost-effectiveness. RESULTS: In the base case analysis, incremental cost-effectiveness ratios (ICER) for the clopidogrel + phenotype, genotype + liberal ticagrelor, and universal ticagrelor strategies were $12,119/QALY, $29,412/QALY, and $142,456/QALY, respectively. Genotype + conservative ticagrelor and genotype + phenotype were not cost-effective due to second-order dominance. Genotype + liberal ticagrelor compared to clopidogrel + phenotype demonstrated the highest acceptance (97%) at a willingness to pay (WTP) threshold of $100,000/QALY. CONCLUSION: Cost-effective strategies to personalize P2Y12 inhibition in ACS include clopidogrel +phenotype and genotype + liberal ticagrelor. Universal ticagrelor may be considered cost-effective at a higher WTP threshold ($150,000/QALY). Genotype + liberal ticagrelor exhibited the highest acceptability compared to clopidogrel + phenotype over the widest range of WTP thresholds and may be preferred.

Comparison of 6-Month Costs Between Oral Antiplatelet Agents Following Acute Coronary Syndrome.

BACKGROUND: In patients with acute coronary syndrome (ACS) treated with percutaneous coronary intervention (PCI), newer antiplatelet agents prasugrel and ticagrelor have lower rates of cardiovascular events when compared with clopidogrel. However, it is unclear whether there are differences in economic outcomes when comparing these agents in ACS-PCI patients. OBJECTIVE: To assess aggregated costs and medical resource utilization among ACS-PCI patients prescribed prasugrel, ticagrelor, or generic clopidogrel, using a large commercial insurance claims database. METHODS: Costs attributable to any medical and pharmacy service and resource utilization including number of admissions, length of hospital stay, emergency room visits, and office visits over the 180-day postdischarge period were compared. All-cause and cardiovascular health care costs and resource utilization were separately analyzed for patients enrolled in the data over the continuous follow-up (CFU) period, and for patients continuously taking their initial treatment for 6 months (CTX). Potential confounders collected over a 6-month baseline assessment period were controlled for, using a generalized linear model. RESULTS: Over the 180-day follow-up, prasugrel and ticagrelor patients underwent fewer admissions (rate ratio [RR] = 0.87, 95% CI = 0.80-0.95) from CFU and RR = 0.81, 95% CI = 0.71-0.89 from CTX) compared with clopidogrel patients. The newer agent cohort incurred more overall health care costs than the generic clopidogrel group, with added costs of $957 (95% CI = $236-$1,725) in the CFU group and $1,122 (95% CI = $455-$1,865) in the CTX group, which were smaller than the increase in all-cause outpatient pharmacy costs associated with the newer agents versus clopidogrel (CFU: $1,175, 95% CI = $1,079-$1,278 and CTX: $1,360, 95% CI = $1,256-$1,487). Overall, there was no statistically significant difference in the economic outcomes associated with prasugrel and ticagrelor. There were, however, significant correlations between all-cause and cardiovascular-related outcomes. CONCLUSIONS: The higher price of prasugrel and ticagrelor was partially offset by a decrease in hospital admission compared with generic clopidogrel over a 6-month postdischarge period. Aggregated medical costs and resource utilization were not significantly different between prasugrel and ticagrelor patients. DISCLOSURES: No funding was received for this study. DiDomenico has received an honorarium from Amgen for preparation of a heart failure drug monograph for Pharmacy Practice News and serves as an advisory board member for a heart failure program at Otsuka America Pharmaceuticals and for Novartis Pharmaceuticals. Touchette has received unrestricted grant funding from Cardinal Health, Sunovion Pharmaceuticals, and Takeda and has served as a consultant to and director of the American College of Clinical Pharmacy Practice-Based Research Network on a study funded by Pfizer. Walton has served as a paid consultant for Bristol-Myers Squibb, Baxter, Merck, Genentech, Primus, Takeda, and Abbott. The other authors have nothing to disclose.

Cost-Effectiveness Analysis of Sacubitril/Valsartan for the Treatment of Heart Failure with Reduced Ejection Fraction in the United States.

OBJECTIVE: Sacubitril/valsartan (SAC/VAL) has been shown to reduce mortality and hospitalization in patients with heart failure with reduced ejection fraction (HFrEF) compared with enalapril but at a substantially higher cost. This study evaluates the cost-effectiveness of SAC/VAL versus enalapril in patients with HFrEF over a 5-year time horizon from the U.S. payer perspective. METHODS: A cohort-based Markov model was developed to compare costs and quality-adjusted life years (QALYs) between SAC/VAL and enalapril in patients with HFrEF over a 5-year time horizon. Markov states included New York Heart Association (NYHA) class (II-IV) and death. Treatment discontinuation, HF-related hospitalizations, and NYHA class progression were modeled as transition states based on data from the PARADIGM trial. Other probabilities, costs, and utilities were obtained from published literature and public databases. RESULTS: In the base case analysis, SAC/VAL cost more than enalapril ($81,943 vs $67,287) and was more effective (2.647 QALYs vs 2.546 QALYs), resulting in an incremental cost-effectiveness ratio of $143,891/QALY gained. At a willingness to pay (WTP) of $100,000/QALY, SAC/VAL was cost-effective up to a cost of $298/month. Results were most sensitive to SAC/VAL cost, SAC/VAL mortality benefit, and NYHA progression probability. SAC/VAL had a 10% and 52% probability of being cost-effective at WTP thresholds of $100,000/QALY and $150,000/QALY, respectively. CONCLUSIONS: SAC/VAL is associated with clinical benefit and may be cost-effective compared with the current standard of care over realistic treatment durations from the payer perspective. Results of this analysis can inform discussions on the value and position of SAC/VAL in the current market.

Clinical pharmacy services in heart failure: an opinion paper from the Heart Failure Society of America and American College of Clinical Pharmacy Cardiology Practice and Research Network.

BACKGROUND: Heart failure (HF) care takes place in multiple settings, with a variety of providers, and generally involves patients who have multiple comorbidities. This situation is a "perfect storm" of factors that predispose patients to medication errors. METHODS AND RESULTS: The goals of this paper are to outline potential roles for clinical pharmacists in a multidisciplinary HF team, to document outcomes associated with interventions by clinical pharmacists, to recommend minimum training for clinical pharmacists engaged in HF care, and to suggest financial strategies to support clinical pharmacy services within a multidisciplinary team. As patients transition from inpatient to outpatient settings and between multiple caregivers, pharmacists can positively affect medication reconciliation and education, assure consistency in management that results in improvements in patient satisfaction and medication adherence, and reduce medication errors. For mechanical circulatory support and heart transplant teams, the Centers for Medicare and Medicaid Services considers the participation of a transplant pharmacology expert (e.g., clinical pharmacist) to be a requirement for accreditation, given the highly specialized and complex drug regimens used. Although reports of outcomes from pharmacist interventions have been mixed owing to differences in study design, benefits such as increased use of evidence-based therapies, decreases in HF hospitalizations and emergency department visits, and decreases in all-cause readmissions have been demonstrated. Clinical pharmacists participating in HF or heart transplant teams should have completed specialized postdoctoral training in the form of residencies and/or fellowships in cardiovascular and/or transplant pharmacotherapy, and board certification is recommended. Financial mechanisms to support pharmacist participation in the HF teams are variable. CONCLUSIONS: Positive outcomes associated with clinical pharmacist activities support the value of making this resource available to HF teams.

Discharge counseling for patients with heart failure or myocardial infarction: a best practices model developed by members of the American College of Clinical Pharmacy's Cardiology Practice and Research Network based on the Hospital to Home (H2H) Initiative.

Hospital to Home is a quality-based initiative led by the American College of Cardiology and the Institute for Healthcare Improvement, aimed at reducing 30-day hospital readmission rates for patients with heart failure or myocardial infarction. Several factors have been shown to attribute to early readmission for these conditions including comorbidities, environmental factors, insufficient discharge planning, lack of health literacy, and nonadherence to drug therapy. Pharmacists play a significant role in reducing readmissions by ensuring that appropriate evidence-based pharmacotherapy regimens have been prescribed during hospitalization; monitoring for drug duplications, medication errors, and adverse reactions; and performing medication reconciliation. Studies have demonstrated the role of pharmacists in reducing medication-related visits to the emergency department as well as hospital readmissions, solely by preventing adverse drug events. Although all of these factors impact early readmissions, providing quality counseling to the patient as well as the patients' caregiver(s) at discharge is critical in order to optimize adherence as well as outcomes. In order to accomplish the goal of reducing readmissions, health care providers must partner together across the continuum of care and include pharmacists as pivotal members of the health care team. In this best practice statement, we summarize key components of discharge counseling for patients with heart failure or myocardial infarction including medication use, medication dose and frequency, drug interactions, medications to avoid, common adverse effects, role of the medication in the disease state, signs and symptoms of the disease, diet, the patient's role in self-care (lifestyle modifications), and when patients should seek medical advice.

Comparison of rate control versus rhythm control for management of atrial fibrillation in patients with coexisting heart failure: a cost-effectiveness analysis.

STUDY OBJECTIVE: To compare lifetime costs and health outcomes of rate control versus rhythm control for management of atrial fibrillation in patients with coexisting heart failure from the third-party payer perspective. DESIGN: A Markov decision analysis model constructed from costs, utility, and transition probability inputs obtained from randomized clinical trials and publically available databases. PATIENTS: A simulated cohort aged 65 years or older with persistent or paroxysmal atrial fibrillation and heart failure. MEASUREMENTS AND MAIN RESULTS: Markov states for rhythm control were cardioversion plus amiodarone and maintenance amiodarone, and those for rate control were ß-blocker, digoxin, and calcium channel blocker. Transition states included treatment success, hospitalizations for atrial fibrillation and/or heart failure, and severe adverse effects. Economic inputs included cost for drugs, cost of hospitalizations for atrial fibrillation and/or heart failure, and cost of management of severe adverse effects. Costs were measured in 2009 U.S. dollars, and clinical outcomes in quality-adjusted life-years (QALYs). One-way and multivariable sensitivity analyses were conducted. Uncertainty intervals (UIs) were obtained from probabilistic sensitivity analyses. Rate control was found to be less costly and more effective than rhythm control. Base case and probabilistic sensitivity analyses cost and effectiveness values for rate control were $7231 (95% UI $5517-9016) and 2.395 QALYs (95% UI 2.366-2.424 QALYs); whereas those for rhythm control were $16,291 (95% UI $11,033-21,434) and 2.197 QALYs (95% UI 2.155-2.237 QALYs). No critical values were found for any model parameters in the one-way sensitivity analyses. The cost-effectiveness acceptability curves showed that rate control was considered cost-effective in 100% of cases at willingness-to-pay ratios between $0 and $200,000/QALY. CONCLUSION: Rate control is less costly and more effective than rhythm control and should be the initial treatment for atrial fibrillation among patients with coexisting heart failure.

Impact of treatment guidelines on clinical and economic outcomes of acute decompensated heart failure.

BACKGROUND: No data exist that demonstrate the impact of comprehensive acute decompensated heart failure (ADHF) treatment guidelines on clinical and economic outcomes in hospitalized patients with this condition. OBJECTIVES: To compare clinical and economic outcomes before and after implementation of treatment guidelines for ADHF. METHODS: A single-center, retrospective, chart review study was conducted in a university hospital. ADHF treatment guidelines were developed and implemented on January 1, 2004. Patients hospitalized for ADHF between January 2003 and November 2004 were identified using the Acute Decompensated Heart Failure Registry. Study periods were 12 months prior to and the 11 months following guideline implementation. RESULTS: This cohort was comprised of 683 ADHF hospitalizations (357 preguideline, 326 postguideline); several patients were admitted more than once. There was a trend toward increased use of intravenous vasoactive drugs (VADs) following guideline implementation (19.9% vs 24.2%; p = 0.05). The duration of intravenous VAD use decreased by more than 40% following guideline implementation, but this was not statistically significant after risk adjustment (p = 0.22). The need for intensive care unit monitoring decreased from 45.1% before guideline implementation to 25.3% following guideline implementation (p < 0.02) in patients treated with intravenous VADs. The need for mechanical ventilation was reduced by nearly 80% (p = 0.04) following guideline implementation. Significantly more patients of the postguideline cohort were prescribed beta-blockers at discharge (54.9% vs 75.2%; p = 0.0001). Costs were not significantly different between the groups. CONCLUSIONS: Implementation of ADHF treatment guidelines was associated with reduced need for mechanical ventilation, improved utilization of beta-blockers at discharge, and trends toward increased use of intravenous VADs, while not significantly changing total costs. More rigorous studies need to be conducted to estimate the true effect of treatment guidelines on ADHF care and outcomes.

Hospital policies for treatment of acute decompensated heart failure.

BACKGROUND: It is unclear to what extent hospitals use guidelines or protocols in treating acute decompensated heart failure (ADHF) and whether nesiritide is included in these guidelines or protocols. OBJECTIVE: To assess the formulary status of currently used drugs, therapeutic guidelines, and perceptions about the appropriateness of treatment of ADHF in community hospitals. METHODS: A Web-based survey of pharmacy directors at community hospitals that were part of a national group purchasing organization was conducted. RESULTS: One hundred seven hospitals participated in the survey (response rate 47.1%). Diuretics such as furosemide and bumetanide were more commonly included (100% and 94.4%, respectively) on hospital formularies than was torsemide (69.2%). Dopamine and dobutamine were more common (94.4% each) on the formulary than was milrinone (68.2%). Nitroprusside and nitroglycerin were listed on the formularies of more than 90% of participating institutions, while nesiritide was listed on the formularies in only 48.6% of hospitals and was placed on restricted status in 36.4% of hospitals. Guidelines for care of patients with ADHF were used in the emergency department (ED), inpatient care units, and outpatient clinics in 18.6%, 43.0%, and 8.5% of hospitals, respectively. Overall, ADHF care, including general treatment as well as specific use of nesiritide, was deemed appropriate in the majority of patients, but nearly twice as many respondents perceived the management of ADHF and specific use of nesiritide as inappropriate in the ED compared with inpatient treatment. Only 41.1% of the respondents reported following Braunwald recommendations for the use of nesiritide. CONCLUSIONS: A sizable percentage of responding community hospitals do not have guidelines for treatment of ADHF despite the existence of such guidelines in the literature. There are opportunities for improvement in the general treatment of ADHF as well as for the use of nesiritide in ADHF, especially in the ED or observation unit versus inpatient units.

Reimbursement mechanisms for glycoprotein IIb/IIIa-receptor inhibitors.

Changes in health care reimbursement policies as they apply to glycoprotein (GP) IIb/IIIa-receptor inhibitors are discussed. GP IIb/IIIa-receptor inhibitors significantly reduce the frequency of myocardial infarction and death in patients with non-ST-segment-elevation (NSTE) acute coronary syndromes (ACSs) and in those undergoing percutaneous coronary intervention (PCI). GP IIb/IIIa-receptor inhibitors are increasingly being used in ambulatory settings, such as the emergency department and the cardiac catheterization laboratory. Recent public policy decisions now provide appropriate reimbursement mechanisms for the outpatient use of GP IIb/IIIa-receptor inhibitors. As a result, small community hospitals and large tertiary care centers can both be appropriately reimbursed for these agents. In August 2000, the Center for Medicare and Medicaid Services developed the Ambulatory Payment Classification system. This system provides compensation for GP IIb/IIIa-receptor inhibitor acquisition and administration and is of special benefit to community hospitals. In addition, recent revisions to the inpatient prospective reimbursement (Diagnosis-Related Group) system increased payment for the use of an early aggressive (invasive) strategy in these patients. Together, these reimbursement mechanisms facilitate the early use of GP IIb/IIIa-receptor inhibitors in patients with NSTE ACSs and in those undergoing PCI. Recent policy changes facilitate reimbursement of hospitals for the use of GP IIb/IIIa-receptor inhibitors.

Preventing exacerbation of an ADE with automated decision support.

This case demonstrates that, despite physician disregard of appropriate expert system warnings during computerized physician order entry, the distribution of alert "override" warnings to non-physician members of the clinical team can help avert adverse drug events.