An economic analysis of tolvaptan compared with fluid restriction among hospitalized patients with hyponatremia.

OBJECTIVE: The vasopressin-receptor antagonist tolvaptan is used for the treatment of hyponatremia (HN) in hospitalized patients with congestive heart failure (CHF) or syndrome of inappropriate antidiuretic hormone secretion (SIADH). The objective of this economic modeling study was to assess the potential cost and health outcomes associated with tolvaptan in comparison with fluid restriction (FR). METHODS: A decision-analytic model was developed to estimate potential cost and health outcomes associated with tolvaptan compared with FR among hospitalized CHF and SIADH patients with severe HN (serum sodium [SS] levels < 125 mEq/L). The model, which was populated with data from the published literature, assumes that response to treatment influences hospital length of stay, probability of an intensive care unit (ICU) admission, and probability of a 30-day all-cause hospital readmission. One-way and probabilistic sensitivity analyses (PSAs) assessed the influence of parameter uncertainty on model results. RESULTS: Model results suggest that, among hospitalized CHF patients with severe HN, the use of tolvaptan compared with FR may lead to reductions of 7.2% and 4.6% in ICU admissions and 30-day readmissions, respectively. Compared with FR, tolvaptan may result in total cost-savings of $156 per hospitalized CHF patient. Among hospitalized SIADH patients with severe HN, the model suggested reductions of 14.6% and 5.1% in ICU admissions and 30-day readmissions, respectively. Compared with FR, tolvaptan may result in total cost-savings of $135 per hospitalized SIADH patient. PSAs found that the probabilities of net cost-savings from the use of tolvaptan compared with FR were 64% and 59% among patients with severe HN with CHF and SIADH, respectively. CONCLUSIONS: Decision-analytic modeling based on published data for hospitalized CHF and SIADH patients with severe HN, indicates that tolvaptan compared with FR has the potential to improve health outcomes and produce cost-savings that more than offset the cost of tolvaptan.

Analyzing Health-Related Quality of Life Data to Estimate Parameters for Cost-Effectiveness Models: An Example Using Longitudinal EQ-5D Data from the SHIFT Randomized Controlled Trial.

INTRODUCTION: The aim of this article is to discuss methods used to analyze health-related quality of life (HRQoL) data from randomized controlled trials (RCTs) for decision analytic models. The analysis presented in this paper was used to provide HRQoL data for the ivabradine health technology assessment (HTA) submission in chronic heart failure. METHODS: We have used a large, longitudinal EuroQol five-dimension questionnaire (EQ-5D) dataset from the Systolic Heart Failure Treatment with the I f Inhibitor Ivabradine Trial (SHIFT) (clinicaltrials.gov: NCT02441218) to illustrate issues and methods. HRQoL weights (utility values) were estimated from a mixed regression model developed using SHIFT EQ-5D data (n = 5313 patients). The regression model was used to predict HRQoL outcomes according to treatment, patient characteristics, and key clinical outcomes for patients with a heart rate ≥75 bpm. RESULTS: Ivabradine was associated with an HRQoL weight gain of 0.01. HRQoL weights differed according to New York Heart Association (NYHA) class (NYHA I-IV, no hospitalization: standard care 0.82-0.46; ivabradine 0.84-0.47). A reduction in HRQoL weight was associated with hospitalizations within 30 days of an HRQoL assessment visit, with this reduction varying by NYHA class [-0.07 (NYHA I) to -0.21 (NYHA IV)]. CONCLUSION: The mixed model explained variation in EQ-5D data according to key clinical outcomes and patient characteristics, providing essential information for long-term predictions of patient HRQoL in the cost-effectiveness model. This model was also used to estimate the loss in HRQoL associated with hospitalizations. In SHIFT many hospitalizations did not occur close to EQ-5D visits; hence, any temporary changes in HRQoL associated with such events would not be captured fully in observed RCT evidence, but could be predicted in our cost-effectiveness analysis using the mixed model. Given the large reduction in hospitalizations associated with ivabradine this was an important feature of the analysis. FUNDING: The Servier Research Group.

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.

Cost-Effectiveness of Ivabradine for Heart Failure in the United States.

BACKGROUND: Ivabradine is a heart rate-lowering agent approved to reduce the risk of hospitalization for worsening heart failure. This study assessed the cost-effectiveness of adding ivabradine to background therapy in the United States from the perspective of a commercial or Medicare Advantage payer. METHODS AND RESULTS: A cost-effectiveness, cohort-based Markov model using a state transition approach tracked a cohort of heart failure patients with heart rate ≥70 beats per minute in sinus rhythm who were treated with ivabradine+background therapy or background therapy alone. Model inputs, including adjusted hazard ratios, rates of hospitalization and mortality, adverse events, and utility-regression equations, were derived from a large US claims database and SHIFT (Systolic Heart failure treatment with the If inhibitor ivabradine Trial). In the commercial population, ivabradine+background therapy was associated with a cost savings of $8594 versus the cost of background therapy alone over a 10-year time horizon, primarily because of reduced hospitalization. Ivabradine was associated with an incremental benefit of 0.24 quality-adjusted life years over a 10-year time horizon. In the Medicare Advantage population, the incremental cost-effectiveness ratio for ivabradine was estimated to be $24 920/quality-adjusted life years. CONCLUSIONS: The cost-effectiveness model suggests that for a commercial population, the addition of ivabradine to background therapy was associated with cost savings and improved clinical outcomes. For a Medicare Advantage population, the analysis indicates that the clinical benefit of ivabradine can be achieved at a reasonable cost.

[Clinical and Economic Efficacy of Ivabradine in Patients Suffered Myocardial Infarction].

OBJECTIVE: to assess the clinical and cost-effectiveness of the addition to the treatment of patients with coronary artery disease, myocardial infarction (MI). If current blocker ivabradine. MATERIAL AND METHODS: as a basis for pharmacoeconomic research results of the program are taken battleships, in which 1226 patients with MI less than 12 months ago, for 16 weeks received ivabradine in addition to standard therapy. When conducting pharmacoeconomic calculations take into account the direct medical and non-medical costs of treating patients with drugs; the call ambulance crews (CAC); on the patients stay in the hospital at admission. To determine the cost of use of ivabradine used data on daily dosages of the drug presented in the program battleships. In this case, using the retail price of drugs taken from the resource pharmindex.ru (date accessed 6/23/14). When calculating the cost of hospitalization and emergency calls using the values specified in the decree of october 18, 2013 No932 "About the state guarantees the free provision of medical care to citizens for 2014 and the planning period of 2015 and 2016.". RESULTS: according to a study LINCOR adding ivabradine to standard therapy resulted in a significant reduction in the frequency of angina attacks, the need for treatment for CACs and hospitalization. Average total cost of a full 16-week course of therapy with a patient ivabradine 1.87 times lower than with the standard therapy alone. The most obvious benefits to health care institutions: the total cost of emergency calls and hospitalization when added to treatment with ivabradine reduced 20,027.79 to 1,630.45 rubles, le 12.3 times. CONCLUSION: despite the increase in direct costs due to the cost of the drug, the addition to the standard therapy of ivabradine in patients with myocardial infarction, pharmaco is more effective than using only standard therapy, due to a significant reduction in the need for emergency calls and hospitalization.

Funding a smoking cessation program for Crohn's disease: an economic evaluation.

OBJECTIVES: Patients with Crohn's disease (CD) who smoke are at a higher risk of flaring and requiring surgery. Cost-effectiveness studies of funding smoking cessation programs are lacking. Thus, we performed a cost-utility analysis of funding smoking cessation programs for CD. METHODS: A cost-utility analysis was performed comparing five smoking cessation strategies: No Program, Counseling, Nicotine Replacement Therapy (NRT), NRT+Counseling, and Varenicline. The time horizon for the Markov model was 5 years. The health states included medical remission (azathioprine or antitumor necrosis factor (anti-TNF), dose escalation of an anti-TNF, second anti-TNF, surgery, and death. Probabilities were taken from peer-reviewed literature, and costs (CAN$) for surgery, medications, and smoking cessation programs were estimated locally. The primary outcome was the cost per quality-adjusted life year (QALY) gained associated with each smoking cessation strategy. Threshold, three-way sensitivity, probabilistic sensitivity analysis (PSA), and budget impact analysis (BIA) were carried out. RESULTS: All strategies dominated No Program. Strategies from most to least cost effective were as follows: Varenicline (cost: $55,614, QALY: 3.70), NRT+Counseling (cost: $58,878, QALY: 3.69), NRT (cost: $59,540, QALY: 3.69), Counseling (cost: $61,029, QALY: 3.68), and No Program (cost: $63,601, QALY: 3.67). Three-way sensitivity analysis demonstrated that No Program was only more cost effective when every strategy's cost exceeded approximately 10 times their estimated costs. The PSA showed that No Program was the most cost-effective <1% of the time. The BIA showed that any strategy saved the health-care system money over No Program. CONCLUSIONS: Health-care systems should consider funding smoking cessation programs for CD, as they improve health outcomes and reduce costs.

Economic evaluation of ivabradine in the treatment of chronic heart failure in Greece.

BACKGROUND: The objective of our study was to assess the cost-effectiveness of ivabradine plus standard care (SoC) in chronic heart failure (CHF) patients with sinus rhythm and a baseline heart rate ≥ 75 b.p.m. in Greece, in comparison with current SoC alone. METHODS: An existing cost-effectiveness model consisting of two health states, was adapted to the Greek health care setting. All clinical inputs of the model (i.e. mortality rates, hospitalization rates, NYHA class distribution and utility values) were estimated from SHIFT trial data. All costing data used in the model reflects the year 2013 (in €). An incremental cost effectiveness ratio (ICER) per quality-adjusted life year (QALY) gained was calculated. Deterministic and probabilistic sensitivity analyses (PSA) were conducted. The horizon of analysis was over patient life time and both cost and outcomes were discounted at 3.5% per year. The analysis was conducted from a Greek third party-payer perspective. RESULTS: The Markov analysis revealed that the discounted quality-adjusted survival was 4.27 and 3.99 QALYs in the ivabradine plus SoC and SoC alone treatment arms, respectively. The cumulative lifetime total cost per patient was €8,665 and €5,873, for ivabradine plus SoC and SoC alone, respectively. The ICER for ivabradine plus SoC versus SoC alone was estimated as €9,986 per QALY gained. The PSA showed that the likelihood of ivabradine plus SoC being cost-effective at a threshold of €36,000/QALY was found to be 95%. CONCLUSIONS: Ivabradine plus SoC may be regarded as a cost-effective option for the treatment in CHF patients in Greece.

[Cost-effectiveness and budget impact of ivabradine in heart failure therapy]. / Costo-utilità e budget impact di ivabradina nella terapia dell'insufficienza cardiaca.

BACKGROUND: Cost-effectiveness of ivabradine was assessed by the National Institute for Health and Clinical Excellence (NICE) in 2012, based on the data derived from the SHIFT trial: NICE considered ivabradine cost-effective for treating chronic heart failure, supporting drug reimbursement by the national healthcare system (NHS). The aim of this study was to assess the cost-effectiveness of ivabradine on top of standard care in heart failure therapy, by adapting a Markovian model to the Italian population and organization, previously developed for submission to national regulatory bodies. METHODS: The demographic and clinical characteristics of the Italian population were derived from both the SHIFT trial and the IN-HF Outcome registry (Italian real practice data). Costs were drawn from the Italian NHS information system. All analyses adopted the Italian NHS perspective. RESULTS: In a lifetime horizon, in the base case, our assessment confirms that adoption of ivabradine seems socially acceptable with a cost per quality-adjusted life year (QALY) of €17,434.86 (incremental cost of €2,952.85 and QALYs gained 0.21). The incremental cost/life-year gained (LYG) is €15,557.24 (LYG gained 0.24) and hospitalization costs avoided are €3,420.77 (avoided hospitalizations 0.76). A probabilistic sensitivity analysis showed that ivabradine on top of standard treatment is cost-effective in more than 87% of cases accepting a threshold of €30,000, and in more than 93% of cases with a threshold of €40,000. CONCLUSIONS: The results obtained for the Italian population and in the organizational context of the Italian NHS show social acceptability (cost per QALY) of ivabradine therapy in the treatment of heart failure.

Cost-effectiveness of tolvaptan for euvolemic or hypervolemic hyponatremia.

PURPOSE: Tolvaptan is clinically effective in increasing serum sodium concentrations for patients with euvolemic or hypervolemic hyponatremia. Appropriate treatment of hyponatremia may reduce the risk of death, hospital resource utilization, and economic burden. The aim of this study was to estimate the cost-effectiveness of tolvaptan treatment in patients who need to be hospitalized for treatment and monitoring of euvolemic or hypervolemic hyponatremia. METHODS: A decision-analytic model was constructed to assess the clinical and economic impact of tolvaptan compared with placebo during a 1-month treatment period. The probabilities, utility weights, resource utilization, and costs in the model were derived from clinical trials, survey research, and the Korean National Health Insurance database. Cost analysis was performed from the perspective of the South Korean health care setting in 2012 Korean won (KRW). The model outcome was the incremental cost per quality-adjusted life-year gained. In addition, subgroup analysis was performed to identify the cost-effectiveness in case of tolvaptan treatment only for patients with marked hyponatremia. Deterministic and probabilistic sensitivity analyses were performed on key model parameters and assumptions. FINDINGS: The total cost per patient was KRW 1,826,771 for tolvaptan treatment and KRW 2,281,926 for placebo. The quality-adjusted life-years for treatment with and without tolvaptan were 0.0481 and 0.0446, respectively. The base-case analysis revealed that tolvaptan was a more effective and less expensive strategy compared with placebo. In the subgroup analysis, this trend was more apparent in case of tolvaptan treatment only for patients with marked hyponatremia. The robustness of the results was confirmed by using deterministic and probabilistic sensitivity analyses. IMPLICATIONS: This cost-effectiveness analysis found that the use of tolvaptan was less expensive and more effective than treatment without tolvaptan in patients with euvolemic or hypervolemic hyponatremia.

A pragmatic, randomized, controlled study evaluating the impact of access to smoking cessation pharmacotherapy coverage on the proportion of successful quitters in a Canadian population of smokers motivated to quit (ACCESSATION).

BACKGROUND: Many smokers find the cost of smoking cessation medications a barrier. Financial coverage for these medications increases utilization of pharmacotherapies. This study assesses whether financial coverage increases the proportion of successful quitters. METHODS: A pragmatic, open-label, randomized, controlled trial was conducted in 58 Canadian sites between March 2009 and September 2010. Smokers (≥10 cigarettes/day) without insurance coverage who were motivated to quit within 14 days were randomized (1:1) in a blinded manner to receive either full coverage eligibility for 26 weeks or no coverage. Pharmacotherapies covered were varenicline, bupropion, or nicotine patches/gum. Investigators/subjects were unblinded to study group assignment after randomization and prior to choosing a smoking cessation method(s). All subjects received brief smoking cessation counseling. The primary outcome measure was self-reported 7-day point prevalence of abstinence (PPA) at week 26. RESULTS: Of the 1380 randomized subjects (coverage, 696; no coverage, 684), 682 (98.0%) and 435 (63.6%), respectively, were dispensed at least one smoking cessation medication dose. The 7-day PPA at week 26 was higher in the full coverage versus no coverage group: 20.8% (n = 145) and 13.9% (n = 95), respectively; odds ratio (OR) = 1.64, 95% confidence interval (CI) 1.23-2.18; p = 0.001. Urine cotinine-confirmed 7-day PPA at week 26 was 15.7% (n = 109) and 10.1% (n = 69), respectively; OR = 1.68, 95% CI 1.21-2.33; p = 0.002. After pharmacotherapy, coverage eligibility was withdrawn from the full coverage group, continuous abstinence between weeks 26 and 52 was 6.6% (n = 46) and 5.6% (n = 38), in the full coverage and no coverage groups, respectively; OR = 1.19, 95% CI 0.76-1.87; p = 0.439. CONCLUSIONS: In this study, the adoption of a smoking cessation medication coverage drug policy was an effective intervention to improve 26-week quit rates in Canada. The advantages were lost once coverage was discontinued. Further study is required on the duration of coverage to prevent relapse to smoking. (clinicaltrials.gov identifier: NCT00818207; the study was sponsored by Pfizer Inc.).

What is the clinical effectiveness and cost-effectiveness of cytisine compared with varenicline for smoking cessation? A systematic review and economic evaluation.

BACKGROUND: Tobacco smoking is one of the leading causes of deaths worldwide. Nearly one-fifth of adults in the UK regularly smoke cigarettes. The ill-health associated with smoking costs the NHS over £3B every year. A number of pharmacological interventions are available that can help people to quit smoking. These include nicotinic receptor partial agonists such as varenicline or cytisine. Varenicline is a synthetic product licensed for use in the UK, while cytisine is derived naturally from the seeds of the plant Cytisus laborinum L. (golden rain acacia). OBJECTIVES: To review the evidence on the clinical effectiveness and safety of cytisine from smoking cessation compared with varenicline; to develop an economic model to estimate the cost-effectiveness of cytisine and varenicline; and to provide recommendations based on value of information analyses as to whether or not a head-to-head trial of cytisine and varenicline would represent effective use of resources. DATA SOURCES: Efficacy and adverse events data were sourced from a recent Cochrane review. These data were supplemented with an updated search of twelve electronic databases, including MEDLINE, EMBASE, Cumulative Index to Nursing and Allied Health Literature and The Cochrane Library, for the period from December 2011 to January 2013. The review included randomised controlled trials (RCTs) of adult smokers attempting to quit using varenicline or cytisine. Further interventions were considered (placebo, nicotine replacement therapy, bupropion) to allow an indirect comparison between varenicline and cytisine. The primary outcome was abstinence at a minimum of 6 months' follow-up. Secondary outcomes were common adverse events such as abnormal dreams, headache, nausea, insomnia and serious adverse events. REVIEW METHODS: A systematic review and network meta-analysis of the clinical evidence was undertaken. A random-effects model was used to allow for heterogeneity between studies. The economic model structure was based on a published model. Probabilistic sensitivity analyses were undertaken to estimate the treatment expected to be most cost-effective given current information. Formal expected value of perfect information, perfect partial information and of sample information were performed. RESULTS: Twenty-three (RCTs) were included in the systematic review, comprising a total of 10,610 participants. Twenty-one trials of varenicline of differing dosing schedules and two trials of cytisine at standard dose met the inclusion criteria. No head-to-head trials comparing varenicline with cytisine were identified. The methodological quality of the studies was judged to be moderate to good. Cytisine was more efficacious than placebo [hazard ratio (HR) 4.27, 95% credible interval (CrI) 2.05 to 10.05], as was standard-dose varenicline (HR 2.58, 95% Crl 2.16 to 3.15). Standard-dose varenicline treatment was associated with significantly higher rates of headache, insomnia and nausea than placebo; there was no significant difference in the rates of abnormal dreams. There were no significant differences in the rates of headache or nausea between cytisine and placebo; data were identified for neither abnormal dreams nor insomnia. Using expected values, cytisine is anticipated to dominate varenicline, in that it produces more quality-adjusted life-years at a lower associated cost. This occurred in approximately 90% of the scenarios performed. However, owing to the large number of people who wish to quit smoking (estimated to be 3 million over a 10-year period), the implications of making an incorrect decision is large. The expected value of sample information indicated that conducting a head-to-head trial of cytisine and varenicline was worthwhile, and that 1000 smokers per arm was an appropriate number to recruit. CONCLUSIONS: On the basis of the evidence included in this review, varenicline and cytisine are both effective interventions to aid smoking cessation when compared with placebo. Cytisine is estimated to be both more clinically effective and cost-effective than varenicline. However, there is uncertainty in the decision, and a head-to-head trial of cytisine and varenicline would appear to be an effective use of resources. STUDY REGISTRATION: The study was registered as PROSPERO CRD42012003455. FUNDING DETAILS: The National Institute for Health Research Health Technology Assessment programme.

Association of out-of-pocket pharmacy costs with adherence to varenicline.

BACKGROUND: Varenicline, a nicotinic acetylcholine receptor partial agonist, is a pharmacotherapy indicated for smoking cessation treatment. To date, no research has examined the relationship between out-of-pocket (OOP) expense and varenicline adherence among Medicare beneficiaries. OBJECTIVES: To (a) characterize medication utilization patterns of varenicline among Medicare members newly initiated on varenicline and (b) examine the relationship between member OOP expense and varenicline medication adherence. METHODS: In this retrospective cohort study, pharmacy claims data were used to identify Medicare Advantage Prescription Drug Plan (MAPD) members newly initiated on varenicline. Demographic and clinical characteristics, varenicline medication utilization patterns, and pharmacy costs (total and varenicline-specific) were determined for members included in the study. Varenicline adherence was measured by calculating the proportion of days covered (PDC) over a period of 84 days (12 weeks) after initiation. Multiple regression analysis was used to examine the relationship between varenicline OOP cost and varenicline medication utilization, while controlling for sociodemographic characteristics, clinical factors, and nonvarenicline pharmacy costs. RESULTS: A total of 15,452 MAPD members were included in the analysis. Mean (SD) subject age was 62.6 (10.0) years; 21.1% (n = 3,256) were dual eligible; and 33.0% (n = 5,106) received a low-income subsidy. Mean (SD) initial varenicline treatment episode duration was 50.8 (37.8) days, with a mean (SD) varenicline days' supply of 47.8 (32.6) obtained by members during the initial treatment episode. Mean (SD) PDC was 0.51 (0.24), and 14.9% (n = 2,302) of members were classified as adherent to treatment (PDC ≥ 0.80). Greater varenicline OOP expense was significantly associated with lower PDC (regression coefficient = -0.058, P less than 0.001) and significantly associated with lower odds of receiving a refill for varenicline (odds ratio 0.594, 95% CI: 0.540-0.655, P less than 0.001). CONCLUSIONS: Among Medicare beneficiaries newly initiated on varenicline, medication adherence was suboptimal, and greater OOP cost was associated with lower adherence and lower odds of refilling varenicline.

The cost effectiveness of ivabradine in the treatment of chronic heart failure from the U.K. National Health Service perspective.

OBJECTIVE: Ivabradine, a specific heart rate lowering therapy, has been shown in a randomised placebo-controlled study, Systolic HF Treatment with the If Inhibitor Ivabradine Trial (SHIfT), to significantly reduce the composite end point of cardiovascular death and hospitalisation for worsening heart failure (HF) in patients with systolic HF who are in sinus rhythm and with a heart rate ≥70 bpm, when added to optimised medical therapy (HR: 0.82, 95% CI 0.75 to 0.90, p<0.0001). We assessed the cost effectiveness of ivabradine, from a UK National Health Service perspective, based on the results of SHIfT. METHODS: A Markov model estimated the cost effectiveness of ivabradine compared with standard care for two cohorts of patients with HF (heart rate ≥75 bpm in line with the EU labelled indication; and heart rate ≥70 bpm in line with the SHIfT study population). Modelled outcomes included death, hospitalisation, quality of life and New York Heart Association class. Total costs and quality adjusted life years (QALYs) for ivabradine and standard care were estimated over a lifetime horizon. RESULTS: The incremental cost per additional QALY for ivabradine plus standard care versus standard care has been estimated as £8498 for heart rate ≥75 bpm and £13 764 for heart rate ≥70 bpm. Ivabradine is expected to have a 95% chance of being cost-effective in the EU licensed population using the current National Institute for Health and Care Excellence cost effectiveness threshold of £20 000 per QALY. These results were robust in sensitivity analyses. CONCLUSIONS: This economic evaluation suggests that the use of ivabradine is likely to be cost-effective in eligible patients with HF from a UK National Health Service perspective.