Pharmacoeconomic evaluation of stroke and myocardial infarction prevention in hypertensive patients: Markov model based on the ACCOMPLISH trial.

OBJECTIVE: We evaluated the pharmacoeconomics of amlodipine combined with benazepril and hydrochlorothiazide combined with benazepril in the treatment of hypertension using a Markov model to provide an evidence-based reference for clinical drug use. METHODS: In this retrospective study, we constructed two types of Markov model using data from the ACCOMPLISH (Avoiding Cardiovascular Events through Combination Therapy in Patients Living with Systolic Hypertension) trial to dynamically simulate the development of hypertension. The models were subjected to rollback analysis and cohort analysis to obtain the cost and effectiveness of the two drug regimens in preventing stroke and myocardial infarction in hypertensive patients. We conducted sensitivity analysis to determine the stability of the results. RESULTS: The cost-effectiveness of amlodipine combined with benazepril was 66,196.97 RMB with 6.59 QALYs and that of hydrochlorothiazide combined with benazepril was 74,588.50 RMB with 6.46 QALYs. The incremental cost-effectiveness ratio of hydrochlorothiazide + benazepril was -64,550.23 compared with amlodipine + benazepril. The amlodipine + benazepril regimen was therefore more cost-effective than hydrochlorothiazide combined with benazepril. The sensitivity analysis results showed that the model was robust. CONCLUSION: Compared with the hydrochlorothiazide + benazepril treatment regimen, the amlodipine + benazepril regimen showed greater economic benefits.

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.

Heart Failure Therapy in 2016: SHIFTing the PARADIGM From Antiquated Therapies Toward Novel Agents.

Heart failure (HF) continues to afflict millions of Americans, resulting in substantial clinical and economic burden to our society. Recent literature has highlighted the role of 2 novel therapies (an angiotensin receptor blocker/neprilysin inhibitor and ivabradine) in further reducing residual disease in HF. Simultaneously, evidence has mounted suggesting that older therapies like digoxin are not effective in contemporary practice and, in fact, may be harmful. This editorial summarizes the most recently published articles pertaining to both new and old HF therapies and provides a call to action to pharmacists on how to shift patients toward effective drug regimens.

Tolvaptan Reduces Long-Term Total Medical Expenses and Length of Stay in Aquaporin-Defined Responders.

The vasopressin type-2 antagonist tolvaptan (TLV) has clinical advantages including amelioration of congestion and normalization of hyponatremia in patients with decompensated heart failure (HF). However, there have been no studies on the cost-effectiveness of TLV therapy. We enrolled 60 consecutive hospitalized patients with stage D HF who received TLV [TLV (+) group], and 60 propensity score-matched HF patients without TLV treatment [TLV (-) group]. We excluded 54 patients who died or received cardiac replacement therapy within 1 year, and finally enrolled 32 patients who received TLV and 34 who did not, who were followed for > 1 year. Among 45 aquaporin-defined responders, whose urine aquaporin-2 relative to plasma arginine vasopressin level was > 1.4 × 10(3) L/g Cre, the TLV (+) group required significantly lower total medical expenses and shorter lengths of stay (LOS) compared with the TLV (-) group [11.2 (1.233.3) versus 31.2 (2.2-71.4) × 10(5) JPY/year, P < 0.001; 30 (0-304) versus 70 (20-221) days, P = 0.030]. In contrast, among the remaining 21 aquaporin-defined non-responders, medical expenses and LOS were comparable irrespective of TLV administration (P = 0.087 and P = 0.407). In conclusion, TLV therapy may reduce total medical expenses in aquaporin-defined responders with stage D 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.

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.

Cost-effectiveness of tolvaptan for the treatment of hyponatraemia secondary to syndrome of inappropriate antidiuretic hormone secretion in Sweden.

BACKGROUND: Tolvaptan is the only vasopressin V2 receptor antagonist licensed by the European Medicines Agency for the treatment of hyponatraemia (HN) secondary to the syndrome of inappropriate antidiuretic hormone secretion (SIADH). We have investigated the cost-effectiveness of tolvaptan versus no active treatment (NAT) in adult patients within the licensed indication who have either failed to respond to fluid restriction or for whom the use of fluid restriction is not suitable, from the societal perspective in Sweden. METHODS: A cost-utility analysis, considering a 'general SIADH' population and two subpopulations of patients (small-cell lung cancer [SCLC] and pneumonia) to broadly represent the complex clinical pathway of SIADH, was performed. A discrete event simulation was developed to model the progression of individuals through inpatient admissions over a 30-day time horizon (180 days for the SCLC cohort). Clinical data were derived from tolvaptan trials and observational data sources. All costs are given in Swedish kronor (SEK). RESULTS: In the 'general SIADH' population, tolvaptan was associated with reduced costs (SEK 5,779 per patient [€624]) and increased quality-adjusted life-years (QALYs) (0.0019) compared with NAT and was therefore the dominant treatment strategy. Tolvaptan was also associated with reduced costs and increased QALYs in the SCLC and pneumonia subpopulations. The most influential variables in our analysis were reduction in hospital length of stay, duration of treatment and long term treatment with tolvaptan in SCLC patients. CONCLUSIONS: Tolvaptan represents a cost-effective treatment option in Sweden for hospitalised patients with HN secondary to SIADH who have either failed to respond to or are unsuitable for fluid restriction.

Ivabradina para o tratamento de insuficiência cardíaca crônica moderada a grave em indivíduos com frequência cardíaca ≥70 bpm e que toleram menos de 50% da dose alvo recomendada de agentes betabloqueadores / Ivabradine for the treatment of moderate to severe chronic heart failure in subjects with heart rate ≥70 bpm and tolerating less than 50% of the recommended target dose of beta-blocking agents

Contexto: A insuficiência cardíaca crônica é uma síndrome sistêmica complexa e progressiva que se caracteriza por comprometimento da perfusão tecidual, com sintomas característicos de dispneia, fadiga, além de piora da qualidade de vida. A síndrome está relacionada a altas taxas de mortalidade e hospitalização. Ivabradina é um protótipo de medicamentos que agem na frequência cardíaca e que recentemente foi aprovada para tratamento de insuficiência cardíaca crônica associada a betabloqueadores em indivíduos em estágios mais avançados da doença e que mantêm a frequência cardíaca alta mesmo em tratamento com as doses mais altas toleradas desses medicamentos. Pergunta: A associação de ivabradina ao tratamento convencional com betabloqueadores é eficaz e segura no tratamento de pacientes com insuficiência cardíaca crônica, quando comparada ao tratamento com betabloqueadores? Evidências científicas: Foram avaliados 15 estudos, dentre os quais um ensaio clínico duplo-cego, randomizado e controlado por placebo no qual se incluíram 6.500 indivíduos com insuficiência cardíaca crônica em estágio funcional NYHA II a IV e frequência cardíaca ≥70 bpm. O tratamento com ivabradina em dose média de 6 mg duas vezes ao dia em associação a betabloqueadores por 23 meses diminuiu o risco de internação por piora no quadro de insuficiência cardíaca em 26%, ao que se associa um NNT de 20 (IC 95% 15 a 31). O medicamento não demonstrou efeito no desfecho primário mortalidade por causas cardiovasculares como também não se observou diminuição de risco de mortalidade por todas as causas. Observou-se uma diminuição no risco de mortalidade por insuficiência cardíaca, desfecho secundário, embora associada à imprecisão importante, em função das baixas taxas de eventos e do amplo intervalo de confiança (NNT 83, IC 95% 52 a 333). Por meio de outros estudos sugere-se que o medicamento tenha efeitos na reversão do remodelamento cardíaco associada à progressividade da doença, diminuição de biomarcadores relacionados à insuficiência cardíaca e na diminuição da pós-carga cardíaca, melhorando o funcionamento ventricular e acoplamento ventrículo arterial, sem, entretanto, interferir na função renal. Identificaram-se efeitos na diminuição da frequência cardíaca e da variação da frequência cardíaca. O uso do medicamento está associado a um NNH de 58 (no período de dois anos) em relação ao desfecho fibrilação atrial em indivíduos com frequência cardíaca maior que 70 bpm. Discussão: O principal benefício do medicamento, cujo efeito foi avaliado por meio de evidência de alta qualidade, é evitar internações por piora no quadro de insuficiência cardíaca. O efeito relativo é de uma diminuição de 26% quando se compara ao uso isolado de betabloqueadores. Entretanto, mesmo para o desfecho de maior benefício, o efeito absoluto ainda é muito baixo, atingindo uma diminuição de 4,9% apenas. Para outros desfechos de hospitalização, o efeito absoluto é ainda mais baixo e mais impreciso. Não houve efeito na mortalidade de forma que o uso do medicamento não obteve efeito nos desfechos mortalidade por todas as causas e por causas cardiovasculares. O efeito estatisticamente significativo observado para diminuição em mortalidade por insuficiência cardíaca partiu de uma medida de baixa qualidade e, portanto, um efeito de baixa confiabilidade e bastante passível de modificação por trabalhos futuros. O medicamento aumenta o risco de fibrilação atrial, como um NNH de 83. Os resultados da análise econômica são frágeis e partem de informações imprecisas, principalmente sobre a estimativa, em termos quantitativos, da população elegível ao tratamento com ivabradina. Decisão: Não incorporar a ivabradina para o tratamento de insuficiência cardíaca crônica moderada a grave em indivíduos com frequência cardíaca ≥ 70 bpm e que toleram menos de 50% da dose alvo recomendada de agentes betabloqueadores, no âmbito do Sistema Único de Saúde - SUS. Foi publicada a Portaria Nº 19, de 24 de maio de 2016.

[Assessment of Efficiency of Medicamentous Therapy in Correction of Structurally Functional Changes of The Cardiac Muscle at Patients With Arterial Hypertension in Combination With Bronchial Asthma].

BACKGROUND: Bronchial asthma (BA) is a serious problem. It was found that the frequency of arterial hypertension (AH) detection in patients with asthma is about 30 %. At patients practically all types of violations of a warm rhythm meet a bronkhoobstruktivny syndrome. Emergence of rather new preparations - If-blockers, opens new opportunities in correction of heart rate (HR) and a cardioprotection at a combination of AH and BA. AIM: To assess therapy diltiazem-retard and ivabradine on structurally functional changes of a cardiac muscle and HR at patients with AH in combination with BA. MATERIAL AND METHODS: Patients (n=91) with BA with AH 1, 2. All patients were outpatients and taken therapy on BA with inhaled corticosteroids. The patients used a 2-agonists. All patients were performed the echocardioscopy on Acuson 128XP/ 10c (USA). Holter monitor ECG (HM-EKG) was found myocardium ischemia - 18 patients, research was continued by 73 persons. The patients were divided into 2 groups. In the first group made n=37, age 53+/-7,64, received diltiazem-retard. The second group included n=36, age 51,2+/-7,13 years - ivabradine. Duration of observation is 12 weeks. RESULTS AND CONCLUSION: Therapy ivabradine and diltiazem at patients BA according to HM-EKG reliable decrease in frequency of registration of ventricular extrasistoliya in days and heart rate (HR) (<0,05), the quantity of supraventricular extrasistoliya per day doubtfully decreased. Diltiazem wasn't more effective concerning decrease in HR, ventricular and supraventricular extrasistoliya, when comparing with ivabradine (>0,05). The result of 12 week therapy ivabradine at patients with a combination of AH and BA more significant was observed in comparison with diltiazem, regression a hypertrophy of the left ventricle, improvement of diastolic function and almost full regression of warm ektopiya. The tendency was to decrease and stabilization arterial pressure and decrease in HR to purpose level.

[Regulatory Adaptive Status in Assessment of Efficacy of Pharmacotherapy and Prognostication of Complications in Functional Class III Chronic Heart Failure].

OBJECTIVE: to elucidate significance of regulatory adaptive status (RAS) for assessment of effectiveness of medical treatment and prediction of cardiovascular complications in functional class (FC) III congestive heart failure (CHF). MATERIAL AND METHODS: We included into this study 100 patients with hypertensive disease (HD) or ischemic heart disease (IHD) and FC III CHF with compromised systolic left ventricular (LV) function. All patients were randomized into two groups. In addition to complex background therapy (quinapril, torasemide, spironolactone) patients of group 1 (n=56, age 57.5+/-21.7 years) were given metoprolol succinate (59.1+/-12.1 mg/day) and patients of group 2 (n=44, age 57.1+/-21.4 years) - ivabradine (12.1+/-4.6 mg/day). Examination at baseline and after 6 months included cardiorespiratory synchronism test (in order to quantitatively define RAS), echocardiography, treadmill test, six minute walk test. Cardiovascular complications (CVC) were registered during 12 months of study treatment. RESULTS: Both schemes of complex therapy equally improved structural and functional state of the myocardium, increased tolerance to physical exercise, reduced neurohumoral hyperactivation. Positive impact on RAS was more pronounced in ivabradine group. Clinical efficacy of therapy as well as number of hospitalizations because of CHF decompensation, ischemic strokes, and cardiovascular deaths did not differ substantially between groups. Initially low or unsatisfactory RAS was associated with higher incidence of CVC while initial unsatisfactory RAS was associated with elevated risk of sudden death. CONCLUSION: The data obtained reflect independent value of determination of RAS for assessment of efficacy of pharmacotherapy and prognosis of CVC in patients with FCIII CHF.

[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.

Characterizing patients with chronic heart failure in community care after hospitalization: a potential role for ivabradine.

AIMS: To identify the prevalence and characteristics of recently hospitalized chronic heart failure (CHF) patients in community care who meet the indication for ivabradine. METHODS: A retrospective clinical audit of CHF patients recently hospitalized with acute decompensated heart failure (ADHF) and subsequently referred to the Tayside Heart Failure Nurse Liaison Service (THFNLS), a Scottish nurse-led community heart failure liaison service. Inclusion criteria were previous hospitalization with ADHF, subsequent referral to the THFNLS, data for ≥ 2 nurse visits, and a recorded pulse. The main outcome measure was the proportion of patients who meet the indicated criteria for ivabradine. RESULTS: In the UK, ivabradine is indicated for CHF with systolic dysfunction in patients in sinus rhythm, with a heart rate ≥ 75 bpm, and NYHA class II-class IV. After up-titration of a beta-blocker, 19.0% of patients in the full dataset (158 of 830) met the indication for ivabradine at the last visit. Of these "ivabradine-suitable" patients, 101 of 158 (63.9%) received bisoprolol "at any time" during the study period; 20 of 158 (12.7%) achieved the target dose (10 mg daily); 52 of 158 (32.9%) received 5 mg or 7.5 mg daily; and 93 of 158 (58.9%) received <5 mg daily. CONCLUSIONS: In this group of Scottish patients previously hospitalized with ADHF and under the care of a protocol-driven clinic, 19% met the indication for ivabradine and may benefit from the increased control of CHF that ivabradine can provide. Among these "ivabradine-suitable" patients, <15% achieved the target dose of beta-blockers, illustrating the substantial clinical need for a well-tolerated and effective therapy such as ivabradine.

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.

Cardiovascular and mortality risks in older Medicare patients treated with varenicline or bupropion for smoking cessation: an observational cohort study.

PURPOSE: To compare cardiovascular and mortality risks in elderly patients treated with varenicline or bupropion for smoking cessation. METHODS: Elderly Medicare beneficiaries were entered into new-user cohorts of varenicline or bupropion for smoking cessation and followed on therapy for primary outcomes of acute myocardial infarction (AMI), stroke, mortality, and a composite of any of these events. Secondary outcomes were unstable angina, coronary revascularization, and a composite of any primary or secondary outcome event. Propensity score stratification was used to adjust for baseline differences in potential confounding factors. Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated using Cox proportional hazards, with bupropion as reference. RESULTS: In cohorts of 74 824 varenicline and 14 133 bupropion users, there were 164 AMI, 96 stroke, 87 death, 317 primary composite, and 814 secondary composite events while on therapy. The HRs (95%CI) were 0.79 (0.50-1.24) for AMI, 1.27 (0.63-2.55) for stroke, 0.58 (0.30-1.13) for death, 0.84 (0.58-1.23) for the primary composite, and 0.92 (0.73-1.14) for the secondary composite. The risk of AMI or the primary composite outcome did not differ in subgroups defined by age, diabetes status, or presence of underlying ischemic heart disease. Only 30% of patients remained on either study drug beyond their first prescription. CONCLUSION: Cardiovascular and mortality risks were not increased in older patients treated with varenicline compared with bupropion for smoking cessation. A potential increase in the risk of stroke with varenicline could not be excluded. Treatment persistence with either drug was low. Published 2014. This article is a U.S. Government work and is in the public domain in the USA.