Economic analysis of ticagrelor therapy from a U.S. perspective: results from the PLATO study.

BACKGROUND: Based on results of the PLATO (Platelet Inhibition and Patient Outcomes) trial comparing ticagrelor with clopidogrel therapy, the U.S. Food and Drug Administration approved ticagrelor in 2011 for reducing thrombotic cardiovascular events in patients with acute coronary syndrome (ACS) with the proviso that it be taken with low-dose aspirin. OBJECTIVES: This study sought to assess the cost and cost effectiveness of ticagrelor therapy relative to clopidogrel in treating ACS patients from the perspective of the U.S. health care system. METHODS: We estimated within-trial resource use and costs using U.S. low-dose aspirin patients in PLATO (n = 547). Quality-adjusted life expectancy was estimated using the total PLATO population (n = 18,624), combined with baseline risk and long-term survival data from an external ACS patient cohort. Study drugs were valued at current costs. Cost effectiveness was assessed, as was the sensitivity of results to sampling and methodological uncertainties. RESULTS: One year of ticagrelor therapy, relative to that of generic clopidogrel, cost $29,665/quality-adjusted life-year gained, with 99% of bootstrap estimates falling under a $100,000 willingness-to-pay threshold. Results were robust to extensive sensitivity analyses, including variations in clopidogrel cost, exclusion of costs in extended years of life, and a recalibrated estimate of survival reflecting a lower underlying mortality risk in the United States. CONCLUSIONS: For PLATO-eligible ACS patients, a U.S. perspective comparison of the current standard of dual antiplatelet therapy of aspirin with clopidogrel versus aspirin plus ticagrelor showed that the ticagrelor regimen increased life expectancy at an incremental cost well within accepted benchmarks of good value for money. (A Comparison of Ticagrelor [AZD6140] and Clopidogrel in Patients With Acute Coronary Syndrome [PLATO]; NCT00391872).

Ticagrelor treatment in patients with acute coronary syndrome is cost-effective in Sweden and Denmark.

OBJECTIVES: To evaluate the cost-effectiveness of treating patients with acute coronary syndromes (ACS) for 12 months with ticagrelor compared with generic clopidogrel in Sweden and Denmark. DESIGN: Decision-analytic model to estimate lifetime costs, life-expectancy, and quality-adjusted life years (QALYs) with ticagrelor and clopidogrel. Event rates, healthcare resource use, and health-related quality of life during 12 months of therapy were estimated from the PLATelet inhibition and patient Outcomes (PLATO) trial. Beyond 12 months, quality-adjusted survival and costs were estimated conditional on events occurring during the 12 months of therapy. When available, country-specific data were employed in the analysis. Incremental cost-effectiveness ratios are presented from a healthcare perspective and a broader societal perspective including costs falling outside the healthcare sector in 2010 local currency. RESULTS: The cost per QALY with ticagrelor compared with generic clopidogrel was SEK 25 022 and DKK 26 892 for Sweden and Denmark, respectively, from a healthcare perspective. The cost per QALY from a broader societal perspective was SEK 24 290 and DKK 25 051 for Sweden and Denmark, respectively. CONCLUSION: The cost per QALY of treating ACS-patients with ticagrelor compared with generic clopidogrel is below the conventional thresholds of cost-effectiveness in Sweden and Denmark.

Cost-effectiveness of treating acute coronary syndrome patients with ticagrelor for 12 months: results from the PLATO study.

AIMS: The efficacy and safety of ticagrelor vs. clopidogrel in patients with acute coronary syndromes (ACS) are well documented in the PLATelet inhibition and patient Outcomes trial (PLATO). The aim of this study was to assess the long-term cost-effectiveness of treating ACS patients for 12 months with ticagrelor compared with generic clopidogrel. METHODS AND RESULTS: Event rates, health-care costs, and health-related quality of life during 12 months of therapy with either ticagrelor or generic clopidogrel were estimated from PLATO. Beyond 12 months, quality-adjusted survival and costs were estimated conditional on whether a non-fatal myocardial infarction (MI), a non-fatal stroke, or no MI or stroke occurred during the 12 months of therapy. Lifetime costs, life expectancy, and quality-adjusted life years (QALYs) were estimated for both treatment strategies. Incremental cost-effectiveness ratios were presented from a health-care perspective in 2010 Euros (€) applying unit costs and life tables from a Swedish setting in the base-case analysis. Treatment with ticagrelor was associated with increased health-care costs of €362 and a QALY gain of 0.13 compared with generic clopidogrel, yielding a cost per QALY gained with ticagrelor of €2753. The cost per life year gained was €2372. The results were consistent in major subgroups. Sensitivity analyses showed a cost per QALY gained with ticagrelor of ∼€7300 under certain scenarios. CONCLUSION: Based on clinical and health-economic evidence from the PLATO study, treating ACS patients with ticagrelor for 12 months is associated with a cost per QALY below generally accepted thresholds for cost-effectiveness. ClinicalTrials.gov Identifier: NCT00391872.

Environmental factors related to the induction of beta-cell autoantibodies in 1-yr-old healthy children.

We studied environmental risk factors which might contribute to the development of beta-cell autoantibodies in healthy children. Here, we investigated 6000 randomly selected children from the large All Babies in Southeast Sweden (ABIS) cohort, including 17 055 newborns recruited between 1997 and 1999. Questionnaires at birth and at 1 yr of age and the levels of autoantibodies to glutamic acid decarboxylase (GADA) and autoantibodies to tyrosine phosphatase (IA-2A) at 1 yr of age were analyzed. The 99th percentile cutoff for autoantibodies was proposed to identify children at risk of type 1 diabetes (T1D) and the 90th percentile cutoff to identify children in whom beta-cell autoimmunity has been induced. Using the 90th percentile cutoff level, 1156 children had either IA-2A (n = 574) or GADA (n = 582), while 126 children had both GADA and IA-2A. When the 99th percentile cutoff level was used, 114 children had either IA-2A (n = 57) or GADA (n = 57), and six children had both GADA and IA-2A. In logistic regression analysis, celiac disease in grandparents [odds ratio (OR) 2.2] and maternal gastrointestinal infection (OR 1.1) represented a risk for simultaneous occurrence of both IA-2A and GADA above the 90th percentile. Birth in spring (March to May) (OR 1.5) and male gender (OR 1.3) were risk factors for induction of IA-2A. Mother's low education represented a risk for induction of IA-2A (OR 1.5) and GADA (OR 1.4). T1D in first-degree relatives increased the risk for beta-cell autoimmunity above the 99th percentile (OR 2.6), whereas type 2 diabetes in grandparents was associated with GADA (OR 2.1). Exposure to cow's milk formulas <2 months of age implied an OR of 2.9 for IA-2A above the 99th percentile.

Comparison of a shiga toxin enzyme-linked immunosorbent assay and two types of PCR for detection of shiga toxin-producing Escherichia coli in human stool specimens.

Shiga toxin (Stx)-producing Escherichia coli (STEC) is a major cause of sporadic cases of disease as well as serious outbreaks worldwide. The spectrum of illnesses includes mild nonbloody diarrhea, hemorrhagic colitis, and hemolytic-uremic syndrome. STEC produces one or more Stxs, which are subdivided into two major classes, Stx1 and Stx2. The ingestion of contaminated food or water, person-to-person spread, and contact with animals are the major transmission modes. The infective dose of STEC may be less than 100 organisms. Effective prevention of infection is dependent on rapid detection of the causative bacterial pathogen. In the present study, we examined 295 stool specimens for the presence of Stx-producing E. coli by three different methods: an Stx enzyme-linked immunosorbent assay, a conventional PCR assay, and a LightCycler PCR (LC-PCR) assay protocol recently developed by our laboratory at the Institute of Medical Microbiology at Hannover Medical School. Our intent was to compare these three methods and to examine the utility of the STEC LC-PCR protocol in a clinical laboratory. The addition of a control DNA to each sample to clearly discriminate inhibited specimens from negative ones enhanced the accuracy of the LC-PCR protocol. From our results, it can be concluded that LC-PCR is a very useful tool for the rapid and safe detection of STEC in clinical samples.