Clinical Characteristics and Incidence of Hemorrhagic Complications in Patients Taking Factor Xa Inhibitors in Spain: A Long-Term Observational Study.

Objective. To analyze the clinical characteristics of patients taking Factor Xa inhibitors (FXai), either direct FXai or enoxaparin (only in active cancer patients), and to estimate the incidence of and risk factors for major bleeding during FXai use. Methods. A retrospective cohort study, which included secondary data from computerized health records of primary care centers and hospitals in seven Spanish Autonomous Communities. Results. 9374 patients were analyzed, with 8972 taking direct FXai and 402 enoxaparin. At baseline, the mean age (SD) was 71.8 (9.4) years, 56.0% were women, 76.3% had hypertension, 33.6% had type 2 diabetes, and 25.5% had heart failure. The most common indication for FXai use was atrial fibrillation (72.3%), followed by venous thromboembolism (22.2%) and non-mechanical cardiac-valve replacement (5.6%). At the end of the follow-up period, the incidence rates of major bleeding overall, gastrointestinal, and intracranial were 10.2, 9.0, and 0.8 per 100 person-years, respectively. The total incidence of fatal major bleeding was 0.5 per 100 person-years. Incidence rates of all bleedings progressively decreased over time, with 62.5% of the first events occurring in the initial three months and reaching 76.8% within six months following initiation of treatment. Only 4.8% of the 1st major bleedings led to death, 2.3% in the case of major gastrointestinal bleeding, and 30.8% after an intracranial bleeding. 65.9% of patients discontinued anticoagulation after experiencing major bleeding. Conclusions. In Spain, patients taking FXai were old and had many comorbidities. Despite incidence rates of major bleeding were high, incidence rates of intracranial and fatal bleedings were low, but more efforts are required due to their relevant clinical impact.

Differences in clinical outcomes, health care resource utilization and costs in heart failure patients according to left ventricular ejection fraction.

INTRODUCTION AND OBJECTIVES: The impact of left ventricular ejection fraction (LVEF) on health care resource utilization (HCRU) and cost in heart failure (HF) patients is not well known. We aimed to compare outcomes, HCRUs and costs according to LVEF groups. METHODS: Retrospective, observational study of all patients with an emergency department (ED) visit or admission to a tertiary hospital in Spain 2018 with a primary HF diagnosis. We excluded patients with newly diagnosed heart failure. One-year clinical outcomes, costs and HCRUs were compared according to LVEF (reduced [HFrEF], mildly reduced [HFmrEF], and preserved [HFpEF]). RESULTS: Among 1287 patients with a primary diagnosis of HF in the ED, 365 (28.4%) were discharged to home (ED group), and 919 (71.4%) were hospitalized (hospital group [HG]). In total, 190 patients (14.7%) had HFrEF, 146 (11.4%) HFmrEF, and 951 (73.9%) HFpEF. The mean age was 80.1±10.7 years; 57.1% were female. The median [interquartile range] of costs per patient/y was €1889 [259-6269] in the ED group and €5008 [2747-9589] in the HG (P <.001). Hospitalization rates were higher in patients with HFrEF in the ED group. The median costs of HFrEF per patient/y were higher in patients in both groups: €4763 [2076-17 155] vs €3900 [590-8013] for HFmrEF vs €3812 [259-5486] for HFpEF in the ED group, and €6321 [3335-796] vs €6170 [3189-10484] vs €4636 [2609-8977], respectively, in the hospital group (all P <.001). This difference was driven by the more frequent admission to intensive care units, and greater use of diagnostic and therapeutic tests among HFrEF patients. CONCLUSIONS: In HF, LVEF significantly impacts costs and HCRU. Costs were higher in patients with HFrEF, especially those requiring hospitalization, than in those with HFpEF.

Risk of outcomes in a Spanish population with chronic kidney disease.

Objectives: To assess mortality and cardiovascular and renal outcomes among patients with chronic kidney disease (CKD) (primary objective), with a particular focus on heart failure (HF) risk following diagnosis of CKD (secondary objective) in Spain. Methods: We conducted an observational study comprising cross-sectional and longitudinal retrospective analyses using secondary data from electronic health records. For the primary objective, adults with prevalent CKD [estimated glomerular filtration rate (eGFR) <60 or ≥60 mL/min/1.73 m2 with a urine albumin:creatinine ratio (UACR) ≥30 mg/g at the index date (1 January 2017)] were included. For the secondary objective, adults with incident CKD in 2017 were enrolled. Results: In the prevalent population, 46 786 patients with CKD without HF [75.8 ± 14.4 years, eGFR 51.4 ± 10.1 mL/min/1.73 m2; 75.1% on renin-angiotensin system inhibitors (RASis)] and 8391 with CKD and HF (79.4 ± 10.9 years, eGFR 46.4 ± 9.8 mL/min/1.73 m2) were included. In the prevalent population, the risk of all-cause death {hazard ratio [HR] 1.107 [95% confidence interval (CI) 1.064-1.153]}, HF hospitalization [HR 1.439 (95% CI 1.387-1.493)] and UACR progression [HR 1.323 (95% CI 1.182-1.481)] was greater in those patients with CKD and HF versus CKD only. For the incident population, 1594 patients with CKD without HF and 727 with CKD and HF were included. Within 24 months from the CKD diagnosis (with/without HF at baseline), 6.5% of patients developed their first HF hospitalization. Although 60.7% were taking RASis, only 3.4% were at maximal doses and among diabetics, 1.3% were taking sodium-glucose cotransporter-2 inhibitors. Conclusions: The presence of HF among CKD patients markedly increases the risk of outcomes. CKD patients have a high risk of HF, which could be partially related to insufficient treatment.

Primary vs. Secondary Heart Failure Diagnosis: Differences in Clinical Outcomes, Healthcare Resource Utilization and Cost.

Background: There is scarce information on patients with secondary heart failure diagnosis (sHF). We aimed to compare the characteristics, burden, and outcomes of sHF with those with primary HF diagnosis (pHF). Methods: Retrospective, observational study on patients ≥18 years with emergency department (ED) visits during 2018 with pHF and sHF in ED or hospital (ICD-10-CM) diagnostic codes. Baseline characteristics, 30-day and 1-year mortality, readmission and re-ED visit rates, and costs were compared between sHF and pHF. Results: Out of the 797 patients discharged home from the ED, 45.5% had sHF, and these presented lower 1-year hospitalization, re-ED visit rates, and costs. In contrast, out of the 2,286 hospitalized patients, 55% had sHF and 45% pHF. Hospitalized sHF patients had significantly (p < 0.01) greater comorbidity, lower use of recommended HF therapies, longer length of stay (10.8 ± 10.1 vs. 9.7 ± 7.9 days), and higher in-hospital and 1-year mortality (32 vs. 25.8%) with no significant differences in readmission rates and lower 1-year re-ED visit rate. Hospitalized sHF patients had higher total costs (€12,262,422 vs. €9,144,952, p < 0.001), mean cost per patient-year (€9,755 ± 13,395 vs. €8,887 ± 12,059), and average daily cost per patient. Conclusion: Hospitalized sHF patients have a worse initial prognosis, greater use of healthcare resources, and higher costs.

Cost-effectiveness analysis of dapagliflozin for the treatment of type 2 diabetes mellitus in Spain: results of the DECLARE-TIMI 58 study.

BACKGROUND: The objective of this study was to carry out a cost-effectiveness analysis of dapagliflozin, as an add-on therapy to standard of care (SoC), for the treatment of type 2 diabetes mellitus (T2DM) in Spain, based on the results of the DECLARE-TIMI 58 trial. METHODS: A discrete event simulation model (Cardiff T2DM) based on the data observed in the DECLARE-TIMI 58 trial was adapted to the Spanish setting to estimate the costs and health outcomes of treatment with dapagliflozin in patients with T2DM who had or were at risk of atherosclerotic cardiovascular disease. Macrovascular events (hospitalization for heart failure, myocardial infarction, stroke, and unstable angina), end-stage renal disease and cardiovascular and non-cardiovascular mortality were modeled according to the survival equations of the DECLARE-TIMI 58 study. Microvascular events (blindness and ulcers) were estimated based on the risk equations of the UK Prospective Diabetes Study. The analysis was conducted from the Spanish National Health System perspective and the time horizon was 30 years. The results were evaluated in terms of cost per quality-adjusted life year (QALY) gained. Only direct health costs were included, and a 3% discount rate was applied to costs and health outcomes. Univariate and probabilistic sensitivity analyses (PSA) were made to assess the robustness of the results. RESULTS: In the main analysis, dapagliflozin was a dominant therapeutic option compared with placebo, with greater effectiveness (0.08 QALYs) and lower associated total costs per patient (€ -2,921). The univariate sensitivity analysis and the PSA confirmed the robustness of the results. The PSA showed the probability that dapagliflozin was a dominant alternative compared with placebo was 84.2% and that it was cost-effective of 92.1%, under a willingness-to-pay of € 20,000/QALY gained. CONCLUSIONS: The analysis of data from the DECLARE-TIMI 58 trial shows that dapagliflozin would be a cost-effective option in Spain for the treatment of adult patients with T2DM, as an add-on therapy to SoC, compared with placebo.

Epidemiology, clinical profile, management, and two-year risk complications among patients with chronic kidney disease in Spain / Epidemiología, perfil clínico, manejo y riesgo de complicaciones a 2 años en pacientes con enfermedad renal crónica en España

Objectives: To describe the epidemiology, clinical profile, treatments, and to determine cardiovascular and renal outcomes after two years of follow-up in a contemporary chronic kidneay disease (CKD) population in Spain. This was also analyzed among the DAPA-CKD-like population (patients who met most inclusion criteria of DAPA-CKD trial). Methods: Observational, retrospective, population-based study using BIG-PAC database. The CKD population was defined as patients ≥18 years, with at least one diagnostic code of CKD prior to the index date (January 1st, 2018). CKD was defined as estimated glomerular filtration rate (eGFR) <60mL/min/1.73m2 (CKD-EPI), or albuminuria >30mg/g. Results: We identified 56,435 CKD patients after exclusions (76.4 years, 52.2% men, urine albumin-to-creatinine ratio 390.8mg/g, eGFR 49.7mL/min/1.73m2). CKD prevalence was 4.91% and incidence 2.10 per 1000 patient-years. Regarding treatments, 69.2% were taking renin-angiotensin system inhibitors (only 4.2% at maximal doses) and 3.5% of diabetic patients SGLT-2 inhibitors. During the two years of follow-up, rates of heart failure, all-cause death, myocardial infarction, stroke, and CKD were 17.9, 12.1, 7.2, 6.3, and 5.9 events per 100 patient-years, respectively. During this period, 44% of patients were hospitalized, and 6.8% died during hospitalization. Cardiovascular outcomes were more common in the DAPA-CKD-like population. Conclusions: In Spain, CKD population is older and comorbidities, including diabetes and heart failure, are common. Cardiovascular and renal outcomes are frequent. There is room for improvement in CKD management, particularly through the use of drugs with proven cardiovascular and renal benefit. (AU)

Objetivos: Describir la epidemiología, el perfil clínico, los tratamientos y los eventos cardiovasculares y renales, tras 2 años de seguimiento en una población contemporánea con enfermedad renal crónica (ERC) en España. También se analizó en la población tipo DAPA-CKD (pacientes que cumplían la mayoría de criterios del estudio DAPA-CKD). Métodos: Estudio observacional, retrospectivo, poblacional, empleando la base de datos BIG-PAC. La población con ERC se definió como pacientes ≥18 años, con al menos un código diagnóstico de ERC antes de la fecha índice (01/01/2018). La ERC se definió como filtrado glomerular estimado (FGe)<60ml/min/1,73m2 (CKD-EPI) o albuminuria >30mg/g. Resultados: Se identificaron 56.435 pacientes con ERC, tras exclusiones (76,4 años, 52,2% varones, cociente albúmina-creatinina 390,8mg/g, FGe 49,7ml/min/1,73m2). La prevalencia fue del 4,91% y la incidencia 2,10/1.000 pacientes/año. El 69,2% tomaba inhibidores del sistema renina-angiotensina (solo el 4,2% a dosis máximas) y el 3,5% de los diabéticos inhibidores SGLT-2. Tras 2 años, las tasas de insuficiencia cardiaca, muerte, infarto de miocardio, ictus y ERC fueron 17,9; 12,1; 7,2; 6,3; 5,9 eventos/100 pacientes/año, respectivamente. Además, el 44% hospitalizaron y el 6,8% murieron durante la hospitalización. Los eventos cardiovasculares fueron más frecuentes en la población tipo DAPA-CKD. Conclusiones: En España, la población con ERC es mayor, y las comorbilidades, incluyendo diabetes e insuficiencia cardiaca, comunes. Los eventos cardiovasculares y renales son frecuentes. Hay margen de mejora en el manejo de la ERC, especialmente a través del empleo de fármacos con beneficio cardiovascular y renal. (AU)

Epidemiology, clinical profile, management, and two-year risk complications among patients with chronic kidney disease in Spain.

OBJECTIVES: To describe the epidemiology, clinical profile, treatments, and to determine cardiovascular and renal outcomes after two years of follow-up in a contemporary chronic kidneay disease (CKD) population in Spain. This was also analyzed among the DAPA-CKD-like population (patients who met most inclusion criteria of DAPA-CKD trial). METHODS: Observational, retrospective, population-based study using BIG-PAC database. The CKD population was defined as patients ≥18 years, with at least one diagnostic code of CKD prior to the index date (January 1st, 2018). CKD was defined as estimated glomerular filtration rate (eGFR) <60mL/min/1.73m2 (CKD-EPI), or albuminuria >30mg/g. RESULTS: We identified 56,435 CKD patients after exclusions (76.4 years, 52.2% men, urine albumin-to-creatinine ratio 390.8mg/g, eGFR 49.7mL/min/1.73m2). CKD prevalence was 4.91% and incidence 2.10 per 1000 patient-years. Regarding treatments, 69.2% were taking renin-angiotensin system inhibitors (only 4.2% at maximal doses) and 3.5% of diabetic patients SGLT-2 inhibitors. During the two years of follow-up, rates of heart failure, all-cause death, myocardial infarction, stroke, and CKD were 17.9, 12.1, 7.2, 6.3, and 5.9 events per 100 patient-years, respectively. During this period, 44% of patients were hospitalized, and 6.8% died during hospitalization. Cardiovascular outcomes were more common in the DAPA-CKD-like population. CONCLUSIONS: In Spain, CKD population is older and comorbidities, including diabetes and heart failure, are common. Cardiovascular and renal outcomes are frequent. There is room for improvement in CKD management, particularly through the use of drugs with proven cardiovascular and renal benefit.

Costs and healthcare utilisation of patients with chronic kidney disease in Spain.

BACKGROUND: Data about the impact of chronic kidney disease (CKD) on health care costs in Spain are scarce This study was aimed to evaluate cumulative costs and healthcare utilisation in CKD in Spain. METHODS: Observational, retrospective, population-based study, which included adults who received care for CKD between 2015 and 2019. Healthcare and medication costs were summarized on a yearly basis starting from the index date (1st January 2015), and then cumulatively until 2019. RESULTS: We identified 44,214 patients with CKD (year 2015: age 76.4 ± 14.3 years, 49.0% women, albumin-to-creatinine ratio 362.9 ± 176.8 mg/g, estimated glomerular filtration rate 48.7 ± 13.2 mL/min/1.73 m2). During the 2015-2019 period, cumulative CKD associated costs reached 14,728.4 Euros, being cardiovascular disease hospitalizations, particularly due to heart failure and CKD, responsible for 77.1% of costs. Total medication cost accounted for 6.6% of the total cost. There was a progressive decrease in cardiovascular disease hospital costs per year (from 2741.1 Euros in 2015 to 1.971.7 Euros in 2019). This also occurred with cardiovascular and diabetic medication costs, as well as with the proportion of hospitalizations and mortality. Costs and healthcare resources use were higher in the DAPA-CKD like population, but also decreased over time. CONCLUSIONS: Between 2015 and 2019, costs of patients with CKD in Spain were high, with cardiovascular hospitalizations as the key determinant. Medication costs were responsible for only a small proportion of total CKD costs. Improving CKD management, particularly with the use of cardiovascular and renal protective medications may be helpful to reduce CKD burden.

Epidemiology, clinical profile, management, and two-year risk complications among patients with chronic kidney disease in Spain.

OBJECTIVES: To describe the epidemiology, clinical profile, treatments, and to determine cardiovascular and renal outcomes after two years of follow-up in a contemporary chronic kidneay disease (CKD) population in Spain. This was also analyzed among the DAPA-CKD-like population (patients who met most inclusion criteria of DAPA-CKD trial). METHODS: Observational, retrospective, population-based study using BIG-PAC database. The CKD population was defined as patients ≥18 years, with at least one diagnostic code of CKD prior to the index date (January 1st, 2018). CKD was defined as estimated glomerular filtration rate (eGFR) <60mL/min/1.73m2 (CKD-EPI), or albuminuria >30mg/g. RESULTS: We identified 56,435 CKD patients after exclusions (76.4 years, 52.2% men, urine albumin-to-creatinine ratio 390.8mg/g, eGFR 49.7mL/min/1.73m2). CKD prevalence was 4.91% and incidence 2.10 per 1000 patient-years. Regarding treatments, 69.2% were taking renin-angiotensin system inhibitors (only 4.2% at maximal doses) and 3.5% of diabetic patients SGLT-2 inhibitors. During the two years of follow-up, rates of heart failure, all-cause death, myocardial infarction, stroke, and CKD were 17.9, 12.1, 7.2, 6.3, and 5.9 events per 100 patient-years, respectively. During this period, 44% of patients were hospitalized, and 6.8% died during hospitalization. Cardiovascular outcomes were more common in the DAPA-CKD-like population. CONCLUSIONS: In Spain, CKD population is older and comorbidities, including diabetes and heart failure, are common. Cardiovascular and renal outcomes are frequent. There is room for improvement in CKD management, particularly through the use of drugs with proven cardiovascular and renal benefit.

Costs and healthcare utilisation of patients with heart failure in Spain.

BACKGROUND: Increasing the knowledge about heart failure (HF) costs and their determinants is important to ascertain how HF management can be optimized, leading to a significant decrease of HF costs. This study evaluated the cumulative costs and healthcare utilisation in HF patients in Spain. METHODS: Observational, retrospective, population-based study using BIG-PAC database, which included data from specialized and primary care of people ≥18 years, from seven autonomous communities in Spain, who received care for HF between 2015 and 2019. The healthcare and medication costs were summarized on a yearly basis starting from the index date (1st January 2015), and then cumulatively until 2019. RESULTS: We identified 17,163 patients with HF (year 2015: mean age 77.3 ± 11.8 years, 53.5% men, 51.7% systolic HF, 43.6% on NYHA functional class II). During the 2015-2019 period, total HF associated costs reached 15,373 Euros per person, being cardiovascular disease hospitalizations the most important determinant (75.8%), particularly HF hospitalizations (51.0%). Total medication cost accounted for 7.0% of the total cost. During this period, there was a progressive decrease of cardiovascular disease hospital costs per year (from 2834 Euros in 2015 to 2146 Euros in 2019, P < 0.001), as well as cardiovascular and diabetic medication costs. CONCLUSIONS: During the 2015-2019 period, costs of HF patients in Spain were substantial, being HF hospitalizations the most important determinant. Medication costs represented only a small proportion of total costs. Improving HF management, particularly through the use of drugs that reduce HF hospitalization may be helpful to reduce HF burden.

Real-life retrospective observational study to determine the prevalence and economic burden of severe asthma in Spain.

Objective: We determined the percentage of patients with severe asthma and exacerbations and evaluated the costs of the disease based on blood eosinophil counts.Methods: A retrospective observational study based on the review of medical records in Spain was carried out. Patients ≥18 years of age requiring care during the years 2014-2015; diagnosed with asthma with at least 2 years of continuous records (at least one year prior to the index date defined as the first asthma medication prescription and at least one year after the index date) were included. Study groups: eosinophil counts <300 cells/µl and ≥300 cells/µl. Main variables: comorbidity, clinical parameters, exacerbations and annual asthma total costs.Results: A total of 268 severe asthmatic patients in Spain were included, representing 6.3% of the asthma population, with 58.6% having eosinophil count ≥300 cells/µl and 41.4% eosinophil count <300 cells/µl. The mean age was 56.1 years (63.4% women). Patients with eosinophilic inflammation (≥300 cells/µl) had lower FEV1 values (54.3% vs. 60.7%; p < .001), poorer treatment adherence (65.6% vs. 77.3%; p < .001), and a greater mean number of exacerbations (3.3 vs. 1.9; p < .001). Exacerbations were correlated to FEV1 (ß=‒.606), eosinophils (ß = .255), immunoglobulin E (ß = .152), and age (ß = .128), p < .001. The mean total asthma annual cost (ANCOVA) was 6222 vs. 4152 euros, respectively (p = .016). Health costs were associated with age (ß = .323), FEV1 (ß = .239), eosinophils (ß = .177) and exacerbations (ß = .158), p < .01.Limitations: Those inherent to retrospective studies; the possible inaccuracy of diagnostic coding referring to severe asthma and other comorbidities and the external validity of the results.Conclusions: Health costs of patients with severe asthma were high. Total annual asthma costs and resource use were greater in patients with ≥300 cells/µl. Age, eosinophilia, exacerbations and FEV1 were associated with greater resource utilization and costs for the health system.

Cost-Effectiveness Analysis of Exenatide versus GLP-1 Receptor Agonists in Patients with Type 2 Diabetes Mellitus.

OBJECTIVE: The aim of this study was to assess the efficiency of exenatide 2 mg/week compared with other glucagon-like peptide-1 (GLP-1) receptor agonists (dulaglutide 1.5 mg/week, liraglutide 1.2 mg/day, liraglutide 1.8 mg/day and lixisenatide 20 µg/day) in adult patients with type 2 diabetes mellitus (T2DM) not adequately controlled on metformin alone from the perspective of the Spanish National Health System (NHS). METHODS: Quality-adjusted life-years (QALYs) gained and total costs of each assessed drug combined with metformin (2 g/day) were estimated over a 40-year time horizon using the Cardiff Diabetes Model (based on UK Prospective Diabetes Study [UKPDS] 68 equations), which simulates disease progression considering the T2DM-related micro- and macrovascular complications, hypoglycaemia, nausea, body mass index (BMI) changes and treatment discontinuation due to adverse effects (AEs). Drug efficacy derived from an indirect comparison performed in a network meta-analysis. Patient characteristics were obtained from the literature. The baseline utility value (0.80) was derived from the PANORAMA study, applying utility decrements to micro- and macrovascular complications, hypoglycaemia episodes and changes in BMI. Treatment discontinuation due to AEs or poorly controlled diabetes (HbA1c > 7.5%) involved switching to second-line (basal insulin) or third-line (basal-bolus insulin) treatment. Total cost (€, 2018) included the costs of drug acquisition, hypoglycaemia, weight gain, micro- and macrovascular complications, nausea and treatment discontinuation due to AEs. An annual discount rate of 3% was applied to costs and outcomes. Deterministic and probabilistic sensitivity analyses (SA) were performed. RESULTS: In base-case, exenatide 2 mg/week resulted in more QALYs (8.26) than dulaglutide 1.5 mg/week (8.19 QALYs), liraglutide 1.2 mg/day (8.10 QALYs), liraglutide 1.8 mg/day (8.20 QALYs) and lixisenatide 20 µg/day (8.13 QALYs). Total cost/patient was €20,423.27 (exenatide 2 mg/week), €22,611.94 (dulaglutide 1.5 mg/week), €21,065.97 (liraglutide 1.2 mg/day), €24,865.69 (liraglutide 1.8 mg/day) and €21,334.58 (lixisenatide 20 µg/day). Deterministic SA confirmed the robustness of the model. In the probabilistic SA, 95-99% of the 1000 Monte Carlo iterations performed were under a hypothetical willingness-to-pay threshold of €20,000/QALY gained. CONCLUSIONS: Exenatide 2 mg/week would be a dominant strategy (more effective and less costly) versus the other GLP-1 receptor agonists assessed for the treatment of T2DM patients who are not adequately controlled on metformin alone.

Cost-Effectiveness of Fixed-Dose Combinations Therapies for Chronic Obstructive Pulmonary Disease Treatment.

BACKGROUND AND OBJECTIVE: Chronic obstructive pulmonary disease (COPD), a progressive lung disorder associated with decline of respiratory function, affects 10.2% of Spanish adults (40-80 years of age). This study aimed to assess the cost-effectiveness of two fixed-dose combinations of long-acting muscarinic antagonist and long-acting ß2-agonist therapies for COPD, with Spanish National Health System perspective. METHODS: A Markov model with five health states based on severity levels defined by GOLD 2010 criteria was used to simulate in monthly cycles the evolution along a 5-year period of a cohort of moderate-to-severe COPD patients, treated with aclidinium-formoterol (ACL/FF) 400/12 µg or tiotropium-olodaterol (TIO/OLO) 5/5 µg fixed-dose combinations. Clinical data on lung-function improvement were obtained from a network meta-analysis and applied to mean baseline forced-expiratory-volume in 1 s (FEV1) for the first 24-weeks period. Natural history for lung-function decline (41 ml/year) was applied until the end of simulation. Risk of exacerbation and pneumonia occurrence were considered. Pharmaceutical costs were calculated with dosages according to indication and public ex-factory prices. The health state-specific disease management and event costs, and utilities were derived from the literature. Total costs (€ 2016) and benefits [life-year-gained (LYG) and quality-adjusted-life-year (QALY)] were discounted (3.0% yearly). Sensitivity analyses were performed. RESULTS: Both therapies provided the same outcomes (4.073 LYG and 2.928 QALY) at 5-year period. ACL/FF 400/12 µg provided marginally lower costs (€ - 332) compared to TIO/OLO 5/5 µg. CONCLUSION: ACL/FF 400/12 µg was a cost-saving therapy in patients with moderate-to-severe COPD in Spain, and provided equivalent effects compared to TIO/OLO 5/5 µg.

Eficiencia de la combinación naproxeno/esomeprazol para el tratamiento de la artrosis en España / Efficiency of naproxen/esomeprazole in association for osteoarthrosis treatment in Spain

Objetivo: Evaluar, desde la perspectiva del Sistema Nacional de Salud, la eficiencia de la combinación a dosis fija de naproxeno y esomeprazol (naproxeno/esomeprazol) en artrosis frente a otros AINE en monoterapia o combinados con un inhibidor de la bomba de protones (IBP). Métodos: Se empleó un modelo de Markov con estados de salud definidos por episodios gastrointestinales (GI): dispepsia, úlcera péptica sintomática o complicada; o cardiovasculares (CV): infarto agudo de miocardio, ictus o insuficiencia cardiaca. El modelo es semejante al utilizado por el NICE en su evaluación de AINE en artrosis publicada en 2008. Se estimaron, en un horizonte temporal de 1 año (ciclos de 3 meses), los costes totales (D , 2012), incluyendo coste farmacológico y de manejo de episodios, y los resultados en salud, expresados en años de vidaajustados por calidad (AVAC), en pacientes mayores de 65 años con riesgo GI aumentado, tras 6 meses de tratamiento con celecoxib (200 mg/día), celecoxib + IBP, diclofenaco (150 mg/día) + IBP, etoricoxib (60 mg/día), etoricoxib + IBP, ibuprofeno (1.800 mg/día) + IBP, naproxeno (1.000 mg/día) + IBP o naproxeno/ esomeprazol (naproxeno 1.000 mg/esomeprazol 40 mg/día). El IBP fue omeprazol (20 mg/día). Resultados: Naproxeno/esomeprazol resultó dominante (más efectivo y menor coste) respecto a celecoxib, etoricoxib y diclofenaco + IBP. Celecoxib + IBP y etoricoxib + IBP fueron más efectivos. Considerando un umbral de 30.000 D /AVAC adicional, naproxeno/esomeprazol resultó coste-efectivo respecto a ibuprofeno + IBP y naproxeno + IBP con valores de relación coste-efectividad incremental de 15.154D y 5.202 D /AVAC adicional, respectivamente. Conclusiones: La combinación a dosis fijas de naproxeno y esomeprazol en pacientes con artrosis y riesgo GI aumentado es una alternativa coste-efectiva e incluso dominante frente a otras opciones (AU)

Objective: To assess, from the perspective of the National Healthcare System, the efficiency of a fixed-dose combination of naproxen and esomeprazole (naproxen/esomeprazole) in the treatment of osteoarthritis (OA) compared to other NSAID, alone or in combination with a proton pump inhibitor (PPI). Methods: A Markov model was used; it included different health states defined by gastrointestinal (GI) events: dyspepsia, symptomatic or complicated ulcer; or cardiovascular (CV) events: myocardial infarction, stroke or heart failure. The model is similar to the one used by NICE in its NSAID evaluation of OA published in 2008 The total costs (D , 2012), including drug and event-related costs, and the health outcomes expressed in quality-adjusted life years (QALY) were estimated in patients with increased GI risk, aged 65 or over, for a 1-year time horizon and a 6-month treatment with celecoxib (200 mg/day), celecoxib + PPI, diclofenac (150 mg/day) + PPI, etoricoxib (60 mg/day), etoricoxib + PPI, ibuprofen (1,800 mg/day) + PPI, naproxen (1,000 mg/day) + PPI or naproxen/esomeprazole (naproxen 1,000 mg/esomeprazole 40 mg/day). The selected PPI was omeprazole (20 mg/day). Results: Naproxen/esomeprazole was a dominant strategy (more effective and less costly) compared to celecoxib, etoricoxib and diclofenac + PPI. Celecoxib + PPI and etoricoxib + PPI were more effective. Considering a cost-effectiveness threshold of D 30,000 per additional QALY, naproxen/esomeprazole was cost-effective compared to ibuprofen + PPI and naproxen + PPI with incremental cost-effectiveness ratios (ICER) of D15,154 and D 5,202 per additional QALY, respectively. Conclusions: A fixed-dose combination of naproxen and esomeprazole is a cost-effective, and even dominant, alternative compared to other options in OA patients with increased GI risk (AU)

Efficiency of naproxen/esomeprazole in association for osteoarthrosis treatment in Spain.

OBJECTIVE: To assess, from the perspective of the National Healthcare System, the efficiency of a fixed-dose combination of naproxen and esomeprazole (naproxen/esomeprazole) in the treatment of osteoarthritis (OA) compared to other NSAID, alone or in combination with a proton pump inhibitor (PPI). METHODS: A Markov model was used; it included different health states defined by gastrointestinal (GI) events: dyspepsia, symptomatic or complicated ulcer; or cardiovascular (CV) events: myocardial infarction, stroke or heart failure. The model is similar to the one used by NICE in its NSAID evaluation of OA published in 2008. The total costs (€, 2012), including drug and event-related costs, and the health outcomes expressed in quality-adjusted life years (QALY) were estimated in patients with increased GI risk, aged 65 or over, for a 1-year time horizon and a 6-month treatment with celecoxib (200mg/day), celecoxib+PPI, diclofenac (150mg/day)+PPI, etoricoxib (60mg/day), etoricoxib+PPI, ibuprofen (1,800mg/day)+PPI, naproxen (1,000mg/day)+PPI or naproxen/esomeprazole (naproxen 1,000mg/esomeprazole 40mg/day). The selected PPI was omeprazole (20mg/day). RESULTS: Naproxen/esomeprazole was a dominant strategy (more effective and less costly) compared to celecoxib, etoricoxib and diclofenac+PPI. Celecoxib+PPI and etoricoxib+PPI were more effective. Considering a cost-effectiveness threshold of €30,000 per additional QALY, naproxen/esomeprazole was cost-effective compared to ibuprofen+PPI and naproxen+PPI with incremental cost-effectiveness ratios (ICER) of €15,154 and €5,202 per additional QALY, respectively. CONCLUSIONS: A fixed-dose combination of naproxen and esomeprazole is a cost-effective, and even dominant, alternative compared to other options in OA patients with increased GI risk.

Cost-effectiveness analysis of rosuvastatin vs generic atorvastatin in Spain.

OBJECTIVE: The objective of this study was to carry out a long-term cost-effectiveness analysis of rosuvastatin compared with generic atorvastatin in the treatment of patients at high cardiovascular (CV) risk (≥ 5% Systematic COronary Risk Evaluation [SCORE]) and patients with prior cardiovascular disease (CVD) in Spain. METHODS: The efficacy data from the Statin Therapies for Elevated Lipid Levels compared Across doses to Rosuvastatin (STELLAR) study were used to simulate achievement of low-density lipoprotein cholesterol targets with different doses of rosuvastatin and generic atorvastatin for an initial period of 1 year. A Markov model was used to estimate the number of CV complications, quality-adjusted life years (QALYs), and healthcare costs (lipid-lowering treatment and CV events) for up to 20 years after initial treatment. The analysis was carried out from the perspective of the Spanish National Health System, with costs (in year 2010 euros) and effects being discounted at 3% per year. RESULTS: Compared with generic atorvastatin, rosuvastatin was cost-effective (cost per QALY gained of less than €30,000) for the primary prevention of CV events in high-risk patients in most sub-groups analyzed. In patients with prior CVD, rosuvastatin was cost-effective in all sub-groups of men and most sub-groups of women. Key limitations of this study were the need to extrapolate data from a single trial to long-term modeled outcomes and the absence of other treatment options in the analysis. CONCLUSIONS: For the treatment of dyslipidemic patients with high CV risk, rosuvastatin is more effective than generic atorvastatin in terms of survival and quality-of-life adjusted survival, with incremental cost-effectiveness ratios within the range generally used in Spain, in most sub-populations defined by various combinations of CV risk factors.

A comparison of budesonide/formoterol maintenance and reliever therapy versus conventional best practice in asthma management in Spain.

OBJECTIVE: To study the effectiveness and safety in a real-life setting of budesonide/formoterol (Symbicort) Maintenance And Reliever Therapy® (Symbicort SMART®), a simplified management approach with one inhaler, compared with conventional best practice (CBP) with multiple inhalers in patients with persistent asthma. DESIGN: Open-label randomized controlled parallel-group trial, 6-month treatment. PARTICIPANTS: A total of 654 adult patients, with persistent asthma receiving treatment with inhaled corticosteroids (ICS), either alone or in conjunction with long-acting ß(2)-agonist. MAIN OUTCOME MEASURES: Time to first severe asthma exacerbation and number of severe asthma exacerbations. RESULTS: No difference between groups was seen in time to first severe exacerbation (p = .2974). Exacerbation rates were low in both groups. A total of 22 patients in the Symbicort SMART group experienced a total of 24 severe asthma exacerbations, and 31 patients in the CBP group experienced a total of 34 severe asthma exacerbations (annual rate 0.16 vs. 0.22, p = .2869). The mean daily dose of ICS expressed in beclomethasone dipropionate equivalent was significantly lower in the Symbicort SMART group (including as-needed use) versus the CBP group (799 µg vs.1184 µg; p < .001). Mean scores in Asthma Control Questionnaire, five-question version, improved significantly in the SMART group compared with the CBP group (p = .0292). Symbicort SMART and CBP were equally well tolerated. The mean drug cost per patient per 6 months was lower for the patients in the SMART group compared with patients receiving CBP (€295.32 vs. €387.98, p < .0001). CONCLUSIONS: A simplified regimen using budesonide/formoterol maintenance and reliever therapy (Symbicort SMART) was at least as effective at improving clinical control compared with CBP with a significantly lower ICS dose and lower drug costs.