Cost-Effectiveness Analysis of Empagliflozin for Treatment of Patients With Heart Failure With Reduced Ejection Fraction in the United States.

BACKGROUND: In the EMPEROR-Reduced trial (Empagliflozin Outcome Trial in Patients with Chronic Heart Failure and a Reduced Ejection Fraction), empagliflozin plus standard of care reduced the composite of cardiovascular death or hospitalization for heart failure versus standard of care in adults with heart failure with reduced ejection fraction. This analysis investigated the cost-effectiveness of the 2 regimens from the perspective of US payors. METHODS AND RESULTS: A Markov cohort model was developed based on Kansas City Cardiomyopathy Questionnaire Clinical Summary Score quartiles and death. Transition probabilities between health states, risk of cardiovascular/all-cause death, hospitalization for heart failure and adverse events, treatment discontinuation, and health utilities were estimated from trial data. Medicare and commercial payment rates were combined for treatment acquisition, acute event management, and disease management. An annual discount rate of 3% was used. Empagliflozin plus standard of care yielded 18% fewer hospitalizations for heart failure and 6% fewer deaths versus standard of care over a lifetime, providing cost-offsets while adding 0.19 life years and 0.19 quality-adjusted life years at an incremental cost of $16 815/patient. The incremental cost-effectiveness ratio was $87 725/quality-adjusted life years gained. Results were consistent across payors, subpopulations, and in deterministic sensitivity analyses. In probabilistic sensitivity analyses, empagliflozin plus standard of care was cost-effective in 3%, 62%, and 80% of iterations at thresholds of $50 000, $100 000, and $150 000/quality-adjusted life years. CONCLUSIONS: Empagliflozin plus standard of care may prevent hospitalizations for heart failure, extend life, and increase quality-adjusted life years for patients with heart failure with reduced ejection fraction at an acceptable cost for US payors.

Public Health Impact and Cost-Effectiveness of Empagliflozin (JARDIANCE®) in the Treatment of Patients with Heart Failure with Preserved Ejection Fraction in France, Based on the EMPEROR-Preserved Clinical Trial.

INTRODUCTION: The efficacy and safety of empagliflozin in the treatment of heart failure with preserved ejection fraction (HFpEF) were demonstrated in the EMPEROR-Preserved trial, which showed a 21% reduction in combined risks of cardiovascular death or HF hospitalization [hazard ratio (HR) 0.79; 95% confidence interval (CI) 0.69-0.90, p < 0.001] and a 27% reduction in the total number of HF hospitalizations (HR 0.73; 95% CI 0.61-0.88, p < 0.001) compared with placebo. On the basis of these results, the present study aimed to assess the cost-effectiveness of empagliflozin + standard of care (SoC) compared with SoC alone in the treatment of HFpEF. METHODS: A published Markov model was adapted to compare the health and economic outcomes in France, considering a collective perspective, in patients treated with empagliflozin in addition to SoC versus patients treated by SoC alone. The model simulated the intention-to-treat (ITT) population of the trial, transitioning between four mutually exclusive health states representing the quartiles of the Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score (KCCQ-CSS). For each arm, the model estimated (over a lifetime time horizon) the economics and the health outcomes (HF hospitalizations avoided, and life years and quality-adjusted life years (QALYs) gained) to calculate the incremental cost-effectiveness ratios (ICERs). The resources used were derived by pairing the FREnch Survey on HF (FRESH) cohort data to French health insurance claims data, and the utilities were derived on the basis of the EQ-5D-5L questionnaire valued on the French tariff. Both economic and health outcomes were discounted at a 2.5% annual rate. RESULTS: The model predicted that treatment of HFpEF patients with empagliflozin would prevent, for 1000 patients treated, 74 HF hospitalizations and 15 deaths attributable to cardiovascular events, resulting on average in a gain of 1 month in overall survival (7.24 versus 7.16 years with placebo) and 0.11 QALYs (6.14 versus 6.03 with placebo). Empagliflozin costs were partially offset by the cost savings from avoided hospitalizations. The ICERs were €18,597 per life year gained and €13,980 per QALY gained. The sensitivity analyses conducted showed that empagliflozin has a 65% probability to be cost-effective under the €25,000/QALY threshold. CONCLUSIONS: The base-case results showed that empagliflozin is a cost-effective strategy for management of HFpEF, in addition to the impact on public health by preventing HF-hospitalizations and deaths in France. Sensitivity analyses suggest that 65% of simulations are under the €25,000/QALY threshold.

Empagliflozin cost-effectiveness analysis in Japanese heart failure with mildly reduced and preserved ejection fraction.

AIMS: Empagliflozin, a sodium-glucose co-transporter 2 inhibitor, was shown to be effective in patients with heart failure with preserved ejection fraction (HFpEF) in the EMPEROR-Preserved trial. The present study aims to evaluate the cost-effectiveness of empagliflozin among Japanese patients with HFpEF. METHODS AND RESULTS: A Markov cohort model was developed to evaluate the cost-effectiveness of empagliflozin added to standard of care (SoC) compared with SoC alone in patients with HFpEF from the perspective of the Japanese healthcare system and with a lifetime horizon. In addition to clinical events, the progression of disease severity was modelled based on the migration of Kansas City Cardiomyopathy Questionnaire-Clinical Summary Scores (KCCQ-CSS). Model inputs, including risk of clinical events, costs, and utilities/disutilities, were derived from EMPEROR-Preserved trial data, a claims database and published literature. The generalizability of model results was investigated by applying various subgroups including age, body mass index (BMI), and region Asia, based on the subgroup analysis of EMPEROR-Preserved data. In the base-case analysis, empagliflozin yielded additional quality-adjusted life years (QALYs; 0.11) with an incremental cost of $1408 per patient for Japanese patients with HFpEF. Incremental cost, mainly derived from drug acquisition cost ($1963 per patient), was largely offset by reduced cost in hospitalization for heart failure (HHF) and cardiovascular death (-$537 per patient and -$166 per patient, respectively). Treatment of empagliflozin provided incremental 0.11 QALYs and 0.08 life years compared with SoC alone. The incremental cost-effectiveness ratio (ICER) was $12 772 (¥1 662 689)/QALY, which was below the Japanese willingness-to-pay (WTP) threshold of $38 408 (¥5 000 000)/QALY. The results were consistent across all the subgroups considered, and empagliflozin was dominant over SoC alone in the region Asia and BMI < 25 kg/m2 subgroups. ICERs for the remaining subgroups ranged from $7520/QALY (¥978 972/QALY, patients with baseline age ≥ 75 years) to $31 049/QALY (¥4 041 896/QALY, patients with baseline New York Heart Association class III/IV). Deterministic sensitivity analysis result showed that the treatment effect on HHF is the biggest driver of the cost-effectiveness analysis, while the ICER will be still under the threshold even if no effect of empagliflozin on HHF was assumed. The probabilistic sensitivity analysis result showed that 64% of simulations were cost-effective based on the Japanese WTP threshold. CONCLUSIONS: Empagliflozin was demonstrated to be cost-effective for patients with HFpEF in Japan based on EMPEROR-Preserved trial data.

Resource utilisation and outcomes of people with heart failure in England: a descriptive analysis of linked primary and secondary care data - the PULSE study.

BACKGROUND: Heart failure (HF) is associated with high levels of resource use and mortality, but prior UK studies have not compared outcomes by HF subtype (HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF)) in large patient populations. This study investigated healthcare resource utilisation and mortality in patients with HF in England, overall and by HF subtype. METHODS: This non-interventional cohort study linked data from the Clinical Practice Research Datalink database to Hospital Episode Statistics inpatient and UK Office for National Statistics mortality data. Patients with a recorded HF diagnosis (new (incident) or existing (prevalent)) based on clinical codes or measures of ejection fraction between 2015 and 2019 were included. RESULTS: Of 383 896 patients identified with HF, 100 224 patients (26%) had a recorded subtype: 68 780 patients with HFrEF (69%) and 31 444 patients (31%) with HFpEF. In total, 918 553 person-years (PY) were included (median follow-up: 2.1 years): 625 619 PY (68%) for unknown HF subtype, 204 862 PY (22%) for HFrEF and 88 017 PY (10%) for HFpEF. Overall, 11% of patients experienced ≥1 HF hospitalisation. After age and sex adjustment, hospitalisations for HF (HHF; including recurrent hospitalisations) and HF-related general practitioner consultations occurred at rates of approximately 80/1000 and 124/1000 PY, respectively, and were highest for patients with HFrEF and unknown subtype. Overall, all-cause and cardiovascular mortality rates were 132/1000 and 49/1000 PY, respectively. Patients with unknown subtype had the highest 1-year and 5-year mortality (20% and 48%), followed by HFrEF (8% and 35%) and HFpEF (6% and 25%). CONCLUSIONS: HF is associated with high levels of healthcare resource use, mortality, HHF and comorbidities. Ensuring that patients receive early and appropriate guideline-directed therapies to manage HF and associated comorbidities is likely to improve patient care and reduce the burden of HF on the English healthcare system.

Multinational cost-effectiveness analysis of empagliflozin for heart failure patients with ejection fraction >40.

AIMS: Heart failure is a chronic progressive condition, with considerable burden on patients' quality of life and economic burden for the healthcare systems. Before the approval of empagliflozin, there were no proven effective treatments for patients with heart failure with left ventricular ejection fraction (HF LVEF) > 40%. The aim of this study was to evaluate the cost-effectiveness of empagliflozin + standard of care (SoC) compared with SoC alone for patients with HF LVEF > 40%, from the perspective of the healthcare systems of the United Kingdom (UK), Spain, and France, and to quantify the healthcare costs for these patients. METHODS AND RESULTS: A lifetime Markov cohort state-transition model was developed based on discrete health states defined by Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score quartiles to track disease severity. Model inputs relied primarily on the EMPEROR-Preserved trial data or obtained from published literature or country-specific databases, as well as local guidelines for the requirements for the conduct of the economic evaluation of healthcare technologies. The total lifetime cost of receiving SoC per patient was £10 092, €15 765, and €14 958 in the UK, Spain, and France, respectively, which increased by £1407, €1148, and €1485, respectively, with the addition of empagliflozin to the SoC. Empagliflozin + SoC was associated with significantly reduced number of hospitalization for HF or cardiovascular death compared with SoC alone, which was a key driver offsetting its drug acquisition costs. The incremental cost-effectiveness ratio per quality-adjusted life year (QALY) gained was consistently favourable at £14 851, €11 706, and €15 447 in the UK, Spain, and France, respectively. Scenario analysis using the New York Heart Association functional class showed similar results. Probabilistic sensitivity analyses showed more than 50% probability for cost-effectiveness for a willingness-to-pay (WTP) threshold of £/€20 000/QALY for the three countries. CONCLUSIONS: Empagliflozin was found to be the first targeted treatment option that is clinically effective and cost-effective for patients with HF LVEF > 40%. Prescribing empagliflozin with SoC to patients with HF LVEF > 40% is expected to improve clinical outcomes and patients' quality of life and substantially below accepted WTP threshold for the healthcare systems in the UK, Spain, and France.

Cost-effectiveness of empagliflozin in heart failure patients irrespective of ejection fraction in England.

AIMS: Heart failure (HF) is a complex syndrome commonly categorized into two main phenotypes [left ventricular ejection fraction (LVEF) below or above 40%], and although empagliflozin is the first approved medication with proven clinical effectiveness for both phenotypes, its cost-effectiveness of treating the entire HF population remains unknown. METHODS: The analysis was performed utilizing two preexisting, LVEF phenotype-specific cost-effectiveness models to estimate the cost-effectiveness of empagliflozin in adults for the treatment of symptomatic chronic HF, irrespective of ejection fraction (EF). The results of the phenotype-specific models were combined using a population-weighted approach to estimate the deterministic and probabilistic incremental cost-effectiveness ratios (ICERs). RESULTS: Based on combined results, empagliflozin + standard of care (SoC) is associated with 6.13 life-years (LYs) and 3.92 quality-adjusted life-years (QALYs) compared with 5.98 LYs and 3.76 QALYs for SoC alone over a lifetime, resulting in an incremental difference of 0.15 LYs and 0.16 QALYs, respectively. Total lifetime healthcare costs per patient are £15 246 for empagliflozin + SoC and £13 982 for SoC giving an incremental difference of £1264. The ICER is £7757/QALY, which is substantially lower than the willingness-to-pay (WTP) of £30 000 per QALY used by NICE. The results of the probabilistic sensitivity analyses are in line with the deterministic results. CONCLUSION: Empagliflozin is the first efficacious, approved, and cost-effective treatment option for all HF patients, irrespective of EF. The combined ICER was consistently below the WTP threshold. Therefore, empagliflozin offers value for money for the treatment of the full HF population in England.

Incidence and prevalence of heart failure in England: a descriptive analysis of linked primary and secondary care data - the PULSE study.

BACKGROUND: Heart failure (HF) is associated with high morbidity and mortality, yet data on HF subtype (HF with reduced ejection fraction [HFrEF] and preserved ejection fraction [HFpEF]) in broad populations are lacking. Additionally, it is unknown whether current HF incidence and prevalence rates are consistent with historical data. Here, we estimate the incidence and prevalence of HF in England and describe the characteristics of patients with HF, both overall and by subtype. METHODS: This was a non-interventional cohort study based on data from the UK Clinical Practice Research Datalink (CPRD), linked to Hospital Episode Statistics data and Office for National Statistics mortality data. Patients aged ≥ 18 years who were registered in the CPRD Aurum database between 1st January 2015 and 31st December 2019 formed the base cohort, from which patients with a recorded chronic HF diagnosis (historical or incident) from 2015-2019 contributed to the incidence and prevalence calculations. RESULTS: The eligible denominator over the study period comprised 11,414,490 patients, from which 383,896 patients with HF were included as prevalent or incident HF cases. From 2015 to 2019, the incidence rate of newly diagnosed HF increased from 4.1/1,000 person-years to 4.9/1,000 person-years, and HF prevalence increased from 2.1% to 2.4%. Phenotype data were available for 100,224 (26.1%) patients, of which 68,780 patients had HFrEF and 31,444 had HFpEF (HFrEF/HFpEF ratio: 70.1%/29.9%). Comorbidity levels were high and broadly similar across HF subgroups. CONCLUSIONS: Primary care recording of HF subtype is suboptimal, with more than 7/10 patients with HF lacking subtype data. In patients with a recorded subtype (n = 100,224), a HFrEF/HFpEF ratio of 70%/30% was observed. Comorbidity levels were high regardless of subtype. Between 2015 and 2019, we observed modest but consistent increases in the incidence and prevalence of chronic HF in adults, in line with historical data.

Cost-effectiveness of adding empagliflozin to the standard of care for patients with heart failure with reduced ejection fraction from the perspective of healthcare system in Malaysia.

Objective: The aim of this study was to determine the cost-effectiveness of adding empagliflozin to the standard of care versus SoC alone for the treatment of patients with heart failure (HF) with reduced ejection fraction (HFrEF) from the perspective of the Ministry of Health of Malaysia. Methods: A cohort-based transition-state model, with health states defined as Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS) quartiles and death, was used to determine the lifetime direct medical costs and quality-adjusted life years (QALYs) for both treatment groups. The risks of all-cause death, cardiovascular death, and health state utilities were estimated from the EMPEROR-Reduced trial. The incremental cost-effectiveness ratio (ICER) was assessed against the cost-effectiveness threshold (CET) as defined by the country's gross domestic product per capita (RM 47,439 per QALY) to determine cost-effectiveness. Sensitivity analyses were conducted to assess the key model parameters' uncertainty in respect to the incremental cost-effectiveness ratio. A scenario analysis was performed using health states as defined by the New York Heart Association classes. Results: Compared to SoC alone, empagliflozin + SoC for the treatment of HFrEF was more expensive (RM 25,333 vs. RM 21,675) but gained more health utilities (3.64 vs. 3.46), resulting in an ICER of RM 20,400 per QALY in the KCCQ-CSS model. A NYHA-based scenario analysis generated an ICER of RM 36,682 per QALY. A deterministic sensitivity analysis confirmed the robustness of the model in identifying the empagliflozin cost as the main driver of cost-effectiveness. The ICER was reduced to RM 6,621 when the government medication purchasing prices were used. A probabilistic sensitivity analysis with a CET of 1xGDP per capita reached 72.9% probability for empagliflozin + SoC against SoC being cost-effective. Conclusion: Empagliflozin + SoC compared to SoC alone for the treatment of HFrEF patients was cost-effective from the perspective of the MoH of Malaysia.

Medical Costs of Chronic Kidney Disease and Type 2 Diabetes Among Newly Diagnosed Heart Failure Patients With Reduced, Mildly Reduced, and Preserved Ejection Fraction.

The economic burden of heart failure (HF) is enormous, but studies of HF costs typically consider the disease to be a single entity. We sought to distinguish the medical costs for patients with HF with reduced ejection fraction (HFrEF), mildly reduced ejection fraction (HFmrEF), and HF with preserved ejection fraction (HFpEF). We identified 16,516 adult patients with an incident HF diagnosis and an echocardiogram from 2005 to 2017 in the electronic medical record of Kaiser Permanente Northwest. Using the echocardiogram nearest to the first diagnosis date, we classified patients with HFrEF (ejection fraction [EF] ≤40%), HFmrEF (EF 41% to 49%), or HFpEF (EF ≥50%). We calculated annualized inpatient, outpatient, emergency, pharmaceutical medical utilization and costs and total costs in $2,020, adjusted for age and gender using generalized linear models, with further analysis of the effects of co-morbid chronic kidney disease (CKD) and type 2 diabetes (T2D). For all HF types, 1 in 5 patients were affected by both CKD and T2D, and costs were significantly higher when both co-morbidities were present. Total per-person costs were significantly higher for HFpEF ($33,740, 95% confidence interval $32,944 to $34,536) than HFrEF ($27,669, $25,649 to $29,689) or HFmrEF ($29,484, $27,166 to $31,800), driven by in- and outpatient visits. Across HF types, visits approximately doubled with the presence of both co-morbidities. Due to greater prevalence, HFpEF accounted for the majority of total and resource-specific treatment costs of HF, regardless of the presence of CKD and/or T2D. In summary, the economic burden was greater per HFpEF patient and was further amplified by co-morbid CKD and T2D. HFpEF accounted for the large majority of total HF costs, underscoring the need to implement effective treatments.

Cost-effectiveness analysis of empagliflozin in patients with heart failure with reduced ejection fraction in Japan based on the EMPEROR-Reduced trial.

BACKGROUND: Several studies have reported the cost-effectiveness of sodium-glucose co-transporter 2 inhibitors in heart failure patients; however, their economic implications have not been sufficiently elucidated in Japan. METHODS: A Markov cohort model was developed to evaluate the cost-effectiveness of empagliflozin plus standard of care (SoC) vs. SoC for patients with heart failure with reduced ejection fraction (HFrEF) in Japan. Model inputs, including risk of clinical events, costs, and utilities based on Kansas City Cardiomyopathy Questionnaire Clinical Summary Scores were derived from EMPEROR-Reduced trial data, published literature, and a claims database. RESULTS: The model predicted lower lifetime hospitalizations for heart failure (HHFs) and additional quality-adjusted life-years (QALYs; 0.21) for empagliflozin plus SoC vs. SoC in the overall population. Increased costs of ¥100,495/patient ($772/patient), primarily driven by higher drug costs of ¥239,558/patient ($1,840/patient), were largely offset by reduced HHF management costs of -¥166,160/patient (-$1,276/patient), yielding an incremental cost-effectiveness ratio (ICER) of ¥469,672/QALY ($3,608/QALY). Results were consistent among subgroups and sensitivity analyses. In probabilistic sensitivity analysis, 82.5 % of runs were below the Japanese ICER reference value of ¥5,000,000/QALY ($38,408/QALY). CONCLUSIONS: Empagliflozin was demonstrated to be cost-effective for HFrEF patients in Japan based on the EMPEROR-Reduced trial data.

Cost-Effectiveness of Empagliflozin on Top of Standard of Care for Heart Failure With Reduced Ejection Fraction in Singapore.

OBJECTIVES: The prevalence of heart failure (HF) and its risk factors are high in Singapore. The EMPEROR-Reduced trial demonstrated that add-on empagliflozin resulted in a reduction in the risk of cardiovascular death or hospitalization for HF compared with standard of care (SoC). This study aimed to estimate the cost-effectiveness of empagliflozin+SoC versus SoC in patients with HF with reduced ejection fraction from a Singaporean healthcare perspective. METHODS: A Markov cohort model simulated progression through health states based on New York Heart Association classes over a lifetime horizon using a cycle length of 1 month. Transition probabilities, and the risk of transient events (hospitalization for HF and cardiovascular/all-cause death) were modeled based on the EMPEROR-Reduced trial. Costs for HF-related events, adverse events, and for monitoring were estimated from a combination of published literature and publicly available fees for public hospitals/polyclinics. RESULTS: Empagliflozin+SoC was estimated to be very cost-effective versus SoC alone with an incremental cost-effectiveness ratio of<8000 Singapore Dollars/quality-adjusted life-year gained. The base-case results were robust as evidenced from the consistency of various scenario and sensitivity analyses performed. When using Kansas City Cardiomyopathy Questionnaire - Clinical Summary Score quartiles as the health states, the incremental cost-effectiveness ratio reduced significantly to 4625 Singapore Dollars/quality-adjusted life-year. CONCLUSION: The use of empagliflozin on top of SoC represents a highly cost-effective solution for the treatment of patients with HF with reduced ejection fraction in Singapore when considering its efficacy, relative affordability, and the growing economic burden of HF in Singapore.

A European multinational cost-effectiveness analysis of empagliflozin in heart failure with reduced ejection fraction.

PURPOSE: This research examined the cost-effectiveness of adding empagliflozin to standard of care (SoC) compared with SoC alone for treatment of heart failure with reduced ejection fraction (HFrEF) from the perspective of healthcare payers in the United Kingdom (UK), Spain and France. METHODS: A lifetime Markov cohort model was developed to simulate patients' progression through health states based on Kansas City Cardiomyopathy Questionnaire Clinical Summary Score. The model predicted risk of death, hospitalisation for worsening heart failure (HHF), treatment-related adverse events, and treatment discontinuation each monthly cycle. Clinical inputs and utilities were derived from EMPEROR-Reduced trial data, supplemented by published literature and national costing databases. Costs (2021 pound sterling/euro) and quality-adjusted life-years (QALYs) were discounted annually for the UK (3.5%), Spain (3.0%) and France (2.5%). RESULTS: In the UK, Spain and France, empagliflozin plus SoC yielded additional QALYs (0.19, 0.23 and 0.21) at higher cost (£1185, €1770 and €1183 per patient) than SoC alone, yielding incremental cost-effectiveness ratios of £6152/QALY, €7736/QALY and €5511/QALY, respectively. Reduced HHF incidence provided most cost offsets for empagliflozin plus SoC. Similar results were obtained for a range of subgroups and sensitivity analyses. Probabilistic sensitivity results indicated empagliflozin plus SoC remained cost-effective vs. SoC at willingness-to-pay thresholds of £20,000/QALY, €20,000/QALY and €30,000/QALY in 79.6%, 75.5% and 97.3% of model runs for the UK, Spain and France, respectively. CONCLUSIONS: Empagliflozin added to SoC leads to health benefits for patients with HFrEF and is a cost-effective treatment option for payers in multiple European countries (UK, Spain, France).

Medication Use for ADHD and the Risk of Driving Citations and Crashes Among Teenage Drivers: A Population-Based Cohort Study.

Objectives: To evaluate the real-world effectiveness of ADHD medications on adverse driving outcomes in teenage drivers with ADHD. Method: We retrospectively followed 15- to 20-year-old ADHD patients with valid driver's license to compare the risk for crashes and citations between periods with and without ADHD medication use, using Florida Medicaid records linked to Department of Motor Vehicles data from 1999 to 2004. Patient-level demographic, clinical, and driver licensing characteristics as well as county-level crash and traffic statistics were adjusted in Cox models. Results: A total of 2,049 patients had 67 crashes and 319 citations. Adjusted hazard ratios comparing ADHD medication use versus no use were 1.22 (95% confidence interval [CI] = [0.66, 1.90]) and 0.89 (95% CI = [0.69, 1.13]) for crashes and citations, respectively. Conclusion: Our study showed no evidence that ADHD medication use was associated with a reduced risk of adverse driving outcomes among teenage drivers enrolled in Medicaid programs. Limitations in interpreting this finding are presented.

Cost-effectiveness of empagliflozin in the UK in an EMPA-REG OUTCOME subgroup with type 2 diabetes and heart failure.

AIMS: Heart failure (HF) and type 2 diabetes (T2D), common co-morbidities, translate into worse patient prognoses and higher direct costs than for either condition alone. Empagliflozin has been shown to markedly reduce cardiovascular (CV) deaths and HF hospitalizations (HHF) in HF patients with T2D. This study evaluated the lifetime cost-effectiveness of supplementing standard of care (SoC) with empagliflozin, relative to SoC alone, in HF patients with T2D from the UK payer perspective. METHODS AND RESULTS: An existing discrete-event simulation model was adapted for the economic evaluation. Risk equations developed from time-dependent parametric survival analyses using patient-level HF subpopulation data from the EMPA-REG OUTCOME trial were employed to predict CV and renal events. Non-CV death, utility weights, and costs were drawn from UK sources. Quality-adjusted life years (QALYs) and costs were discounted at 3.5% per annum. Relative to SoC, empagliflozin with SoC yielded fewer first HHF, recurrent HHF, CV death, and non-fatal myocardial infarction but more non-fatal stroke events. Empagliflozin with SoC vs. SoC alone was associated with increased average life expectancy (10.80 vs. 9.59 LYs) and quality of life (6.27 vs. 5.62 QALYs), though at higher lifetime cost (£18 197 vs. £16 829) per person, resulting in an incremental cost-effectiveness ratio of £2093 per QALY. The probability of empagliflozin being cost-effective in the HF subpopulation at a £20 000 per QALY willingness-to-pay threshold was 91%. CONCLUSIONS: This analysis suggests that adding empagliflozin to SoC in HF patients with T2D constitutes a cost-effective use of UK healthcare resources and may provide long-term health benefits to patients.

Comorbidities and relevant outcomes, commonly associated with cancer, of patients newly diagnosed with advanced non-small-cell lung cancer in Sweden.

OBJECTIVE: The objective was to describe the prevalence of baseline comorbidities in patients with advanced NSCLC and the incidence rate of relevant outcomes commonly associated with NSCLC, and its treatments, in the year after diagnosis. METHODS: A non-interventional cohort study compared adult patients newly diagnosed with advanced NSCLC during 2006-2013 with the general population. The prevalence of comorbidities one year before and incidence of relevant outcomes one year after NSCLC diagnosis were informed by data on all healthcare visits from two large regional registers. Main summary measures were prevalence, median survival, odds ratios (ORs), incidence rate (IR) and mortality rate (MR) with corresponding 95% confidence intervals (CIs). RESULTS: A total of 3,834 NSCLC patients were matched to 15,332 comparators. The prevalence of analysed comorbidities was significantly higher for NSCLC patients compared to the general population, with an OR of 2.44 (95% CI 2.27-2.63). Overall, the majority of IRs were higher for NSCLC patients, compared to the general population. The all-cause MR for the NSCLC cohort was significantly higher leading to an IR ratio of 32.5 (95% CI 31.0-34.2). CONCLUSIONS: Advanced NSCLC patients presented with significantly more comorbidities in the year before diagnosis and relevant outcomes of interest in the year after.

Global named patient use program of afatinib in advanced non-small-cell lung carcinoma patients who progressed following prior therapies.

AIM: A global afatinib named patient use program in non-small-cell lung carcinoma (NSCLC) commenced in 2010. MATERIALS & METHODS: Eligible NSCLC patients had progressed after clinical benefit on prior erlotinib/gefitinib and/or had activating EGFR/HER2 mutations, exhausted all other treatments, and were ineligible for afatinib trials. RESULTS: Data, as of January 2016, were reported on 3966 heavily pretreated NSCLC patients (41 countries; six continents). Among 2595/3966 (65.4%) patients with tumor EGFR status, 2407 (92.8%) were EGFR mutation positive. Median time to treatment failure (2862/3966 [72.2%] patients with available data) was 4.4 months. Among 1141/2862 (39.9%) patients with response reported, objective response rate was 23.4% (267/1141). Safety findings were as expected. CONCLUSION: Time to treatment failure durations and objective response rates were encouraging.

Risk of Suicidal Events With Atomoxetine Compared to Stimulant Treatment: A Cohort Study.

BACKGROUND: Antidepressant effects on increased suicidality in children have raised public concern in recent years. Approved in 2002 for attention-deficit/hyperactivity disorder treatment, the selective noradrenalin-reuptake-inhibitor atomoxetine was initially investigated for the treatment of depression. In post-hoc analyses of clinical trial data, atomoxetine has been associated with an increased risk of suicidal ideation in children and adolescents. We analyzed whether the observed increased risk of suicidal ideation in clinical trials translates into an increased risk of suicidal events in pediatric patients treated with atomoxetine compared with stimulants in 26 Medicaid programs. METHODS: Employing a retrospective cohort design, we used propensity score-adjusted Cox proportional hazard models to evaluate the risk of suicide and suicide attempt in pediatric patients initiating treatment with atomoxetine compared with stimulants from 2002 to 2006. RESULTS: The first-line treatment cohort included 279 315 patients. During the first year of follow-up, the adjusted hazard ratio for current atomoxetine use compared with current stimulant use was 0.95 (95% CI 0.47-1.92, P = .88). The second-line treatment cohort included 220 215 patients. During the first year of follow-up, the adjusted hazard ratio for current atomoxetine use compared with current stimulant use was 0.71 (95% CI 0.30-1.67, P = .43). CONCLUSIONS: First- and second-line treatment of youths age 5 to 18 with atomoxetine compared with stimulants was not significantly associated with an increased risk of suicidal events. The low incidence of suicide and suicide attempt resulted in wide confidence intervals and did not allow stratified analysis of high-risk groups or assessment of suicidal risk associated with long-term use of atomoxetine.

High-dose magnesium sulfate infusion protocol for status asthmaticus: a safety and pharmacokinetics cohort study.

PURPOSE: To assess the safety and pharmacokinetics of high-dose magnesium sulfate (MgSO(4)) infusion in pediatric patients with status asthmaticus. METHODS: A prospective cohort study within a 20-bed pediatric intensive care unit in an academic community hospital. Patients 2-18 years of age admitted with status asthmaticus between 10/2009 and 8/2010 were included in the study. All patients received standard therapy for asthma, while the treatment group received an intravenous magnesium sulfate bolus of 50-75 mg/kg (0.2-0.3 mmol/kg) followed by 40 mg/kg/h (0.16 mmol/kg/h) for 4 h. Patients were monitored for cardiorespiratory complications. The treatment group underwent four blood draws to assess pharmacokinetic parameters. RESULTS: Nineteen patients were in the treatment group and 38 patients in the control group after exclusion criteria and consenting were completed. No clinically significant differences were found between groups. There were no interventions or discontinuations of MgSO(4) due to adverse events. In the treatment group, three patients had mild infusion-related reactions. Heart rate and respiratory rate were statistically significantly lower in the magnesium treatment group. CONCLUSIONS: The continuous infusions of MgSO(4) were safe at the studied doses and maintained serum magnesium (SrMg) and ionized magnesium levels similar to levels required to produce smooth muscle relaxation in other clinical settings. Further studies are needed to investigate the efficacy of high-dose continuous MgSO(4) infusion as an adjunctive treatment for severe asthma treatment and determine the SrMg level required to maintain airway smooth muscle relaxation.

Cardiovascular safety of central nervous system stimulants in children and adolescents: population based cohort study.

OBJECTIVES: To evaluate the cardiac safety of central nervous system stimulants in children and adolescents. DESIGN: Population based retrospective cohort study. SETTING: Automated healthcare claims data from 1,219,847 children and young people eligible for 28 state Medicaid programmes from 1999 to 2006 linked to the Social Security Death Master File and the National Death Index. PARTICIPANTS: Children and young people age 3-18 entered the cohort at the first diagnosis of a mental health condition commonly treated with stimulants (such as attention-deficit/hyperactivity disorder) after a minimum period of six months' eligibility and were followed until loss of eligibility, their 19th birthday, admission to hospital for longer than 30 days, or death. Exclusion criteria included transplant recipients, receipt of dialysis, or claims indicating substance misuse. We retained high risk groups with similar use of stimulants as low risk children (such as children with congenital heart disease). Sociodemographic characteristics, cardiac risk factors, and psychiatric diagnoses obtained from before the index period were summarised with a propensity score. We used discrete survival analysis to estimate the relative risk for periods of stimulant use and non-use, adjusted for propensity score and antipsychotic use for the full cohort and the high risk and low risk groups. MAIN OUTCOME MEASURES: Composite endpoint of stroke, acute myocardial infarction, or sudden cardiac death; a secondary composite endpoint added ventricular arrhythmia RESULTS: A total of 66 (95 including ventricular arrhythmia) events occurred during 2,321,311 years of follow-up. The odds ratio adjusted for propensity score and antipsychotic use for current versus no stimulant use was 0.62 (95% confidence interval 0.27 to 1.44), with a corresponding adjusted incidence rate of 2.2 and 3.5 per 100,000 patient years for current stimulant and non-use, respectively. Twenty six events occurred in high risk patients (incidence rate 63 per 100,000 patient years) with an odds ratio of 1.02 (0.28 to 3.69). Odds ratios for the secondary endpoint were similar to those for the primary endpoint (0.74, 0.38 to 1.46). CONCLUSIONS: Treatment of children with central nervous stimulants is not significantly associated with an increase in the short term risk of severe cardiac events. Analyses cannot be generalised to children with long term use of stimulants. Furthermore, long term effects of slight increases in heart rate or blood pressure are unknown.

Patient counseling practices in U.S. pharmacies: effects of having pharmacists hand the medication to the patient and state regulations on pharmacist counseling.

OBJECTIVES: To determine the amount and type of oral counseling given to shoppers posing as new patients with new prescriptions and to determine how state regulations, pharmacy and pharmacist characteristics, and environmental factors affect oral counseling practices. DESIGN: Cross-sectional, observational, correlational study. SETTING: 41 states and the District of Columbia between January 28 and March 31, 2008. PARTICIPANTS: 365 community pharmacy staff members had interactions with shopper-patients. INTERVENTION: Shoppers presented new prescriptions in community pharmacies and recorded observations related to oral communication with pharmacy staff. MAIN OUTCOME MEASURES: Oral provision of medication information and risk information to shoppers by pharmacy staff, as well as questions asked of shoppers by pharmacy staff. RESULTS: Some form of oral communication related to a medication was reported in 68% of encounters. At least one informational item for either medication was provided for approximately 42% of encounters. At least one risk information item was provided in 22% of encounters. Logistic regression findings indicated that the strongest predictor of oral counseling, either providing information or asking questions, was the pharmacist being the pharmacy staff member who handed the medication to the patient, controlling for all other variables in the models. In addition, having strict state regulations specifying that pharmacists must counsel all patients receiving new prescriptions predicted whether patients received counseling. A more private area for prescription pick up also was a significant predictor. CONCLUSION: The importance of the direct encounter between the pharmacist and patient and strict state regulations mandating that pharmacists counsel patients with new prescriptions were highlighted by these findings.