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      Evaluación económica del tratamiento con ácido acetilsalicílico más esomeprazol comparado con clopidogrel en la prevención de la hemorragia gastrointestinal Translated title: Economic evaluation of the treatment of aspirin plus esomeprazole compared to clopidogrel in gastrointestinal bleeding prevention

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          Abstract

          Objetivo: Evaluar la eficiencia del ácido acetilsalicílico (AAS) más esomeprazol frente a clopidogrel en la prevención de la hemorragia gastrointestinal. Métodos: Análisis coste-efectividad (árbol de decisión de 2 ramas: AAS más esomeprazol y clopidogrel) respecto a la evitación de casos de hemorragia gastrointestinal en 2 años, y análisis de sensibilidad. Resultados: El coste total del tratamiento con AAS más esomeprazol (2.865 S por paciente libre de hemorragia) fue inferior al clopidogrel (2.965 S). El tratamiento con AAS resultó dominante. En todos los análisis de sensibilidad la combinación siguió siendo dominante. Al sustituir esomeprazol 40 mg por omeprazol 40 mg, el coste del tratamiento combinado descendió hasta 1.934S/por episodio evitado. Conclusiones: La asociación de esomeprazol y AAS es más coste-efectiva que clopidogrel en la prevención de la hemorragia gastrointestinal. La combinación con omeprazol resulta aún más coste-efectiva.

          Translated abstract

          Objective: To evaluate the use of aspirin plus esomeprazole vs. clopidogrel in the prevention of gastrointestinal bleeding. Methods: We performed a cost-effectiveness analysis (two-branch decision tree: aspirin plus esomeprazole or clopidogrel) of prevention of gastrointestinal bleeding over a 2-year period, as well as sensitivity analyses. Results: The total cost of aspirin plus esomeprazole treatment (2,865S/patient free of hemorrhage) was lower than that of clopidogrel (2,965S). Aspirin treatment was dominant. The combination continued to be dominant in all sensitivity analyses. When esomeprazole 40 mg was substituted by omeprazole 40 mg, the cost of combination therapy decreased to 1,934 S/prevented hemorrhage. Conclusions: The association of esomeprazole and aspirin is more cost-effective than clopidogrel in preventing gastrointestinal bleeding. Aspirin plus omeprazole was even more cost-effective.

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          Clopidogrel versus aspirin and esomeprazole to prevent recurrent ulcer bleeding.

          Concurrent therapy with a proton-pump inhibitor is a standard treatment for patients receiving aspirin who are at risk for ulcer. Current U.S. guidelines also recommend clopidrogel for patients who have major gastrointestinal intolerance of aspirin. We compared clopidogrel with aspirin plus esomeprazole for the prevention of recurrent bleeding from ulcers in high-risk patients. We studied patients who took aspirin to prevent vascular diseases and who presented with ulcer bleeding. After the ulcers had healed, we randomly assigned patients who were negative for Helicobacter pylori to receive either 75 mg of clopidogrel daily plus esomeprazole placebo twice daily or 80 mg of aspirin daily plus 20 mg of esomeprazole twice daily for 12 months. The end point was recurrent ulcer bleeding. We enrolled 320 patients (161 patients assigned to receive clopidogrel and 159 to receive aspirin plus esomeprazole). Recurrent ulcer bleeding occurred in 13 patients receiving clopidogrel and 1 receiving aspirin plus esomeprazole. The cumulative incidence of recurrent bleeding during the 12-month period was 8.6 percent (95 percent confidence interval, 4.1 to 13.1 percent) among patients who received clopidogrel and 0.7 percent (95 percent confidence interval, 0 to 2.0 percent) among those who received aspirin plus esomeprazole (difference, 7.9 percentage points; 95 percent confidence interval for the difference, 3.4 to 12.4; P=0.001). Among patients with a history of aspirin-induced ulcer bleeding whose ulcers had healed before they received the study treatment, aspirin plus esomeprazole was superior to clopidogrel in the prevention of recurrent ulcer bleeding. Our finding does not support the current recommendation that patients with major gastrointestinal intolerance of aspirin be given clopidogrel. Copyright 2005 Massachusetts Medical Society.
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            Association between aspirin and upper gastrointestinal complications: systematic review of epidemiologic studies.

            Because of the widespread use of aspirin for prevention of cardiovascular diseases, side-effects associated with thromboprophylactic doses are of interest. This study summarizes the relative risk (RR) for serious upper gastrointestinal complications (UGIC) associated with aspirin exposure in general and with specific aspirin doses and formulations in particular. After a systematic review, 17 original epidemiologic studies published between 1990 and 2001 were selected according to predefined criteria. Heterogeneity of effects was explored. Pooled estimates were calculated according to different study characteristics and patterns of aspirin use. The overall relative risk of UGIC associated with aspirin use was 2.2 (95% confidence interval (CI): 2.1, 2.4) for cohort studies and nested case-control studies and 3.1 (95% CI: 2.8, 3.3) for non-nested case-control studies. Original studies found a dose-response relationship between UGIC and aspirin, although the risk was still elevated for doses lower or up to 300 mg day(-1). The summary RR was 2.6 (95% CI: 2.3, 2.9) for plain, 5.3 (95% CI: 3.0, 9.2) for buffered, and 2.4 (95% CI: 1.9, 2.9) for enteric-coated aspirin formulations. Aspirin was associated with UGIC even when used at low doses or in buffered or enteric-coated formulations. The latter findings may be partially explained by channeling of susceptible patients to these formulations.
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              CYP2C19 polymorphism and proton pump inhibitors.

              Proton pump inhibitors such as omeprazole (esomeprazole), lansoprazole, pantoprazole and rabeprazole are eliminated by the hepatic route and the polymorphic CYP2C19 is mainly involved in their metabolism. In different populations three phenotypes have been identified: extensive metabolizers, poor metabolizers and individuals carrying one wild type and one mutant allele (het extensive metabolizers). Systemic exposure to the proton pump inhibitors as expressed by the AUC (area under the plasma level time profiles) is 5-12-times higher in poor metabolizers than in extensive metabolizers. As the pharmacodynamic response (elevation of intragastric pH) to the proton pump inhibitors is related directly to their AUC, a much higher pH can be monitored over 24 hr in poor metabolizers than in extensive metabolizers. Furthermore, clinical efficacy of all proton pump inhibitors depend on maintaining intragastric pH above certain threshold levels and significantly higher eradication rates of Helicobacter pylori have been observed in patients of the poor metabolizers and het extensive metabolizers phenotype if compared to extensive metabolizers. Likewise, limited data suggest that proton pump inhibitors-induced healing rates in gastro-oesophageal reflux disease are apparently higher in poor metabolizers/het extensive metabolizers than in extensive metabolizers of CYP2C19. Therefore initial genotyping for this enzyme and higher dosage in extensive metabolizers is likely to improve the clinical efficacy of proton pump inhibitors.
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                Author and article information

                Journal
                gs
                Gaceta Sanitaria
                Gac Sanit
                Ediciones Doyma, S.L. (Barcelona, Barcelona, Spain )
                0213-9111
                February 2006
                : 20
                : 1
                : 54-57
                Affiliations
                [01] Barcelona orgnameQuímica Farmacéutica Bayer, S.A. orgdiv1Unidad de Farmacoeconomía y Relaciones Institucionales España
                Article
                S0213-91112006000100009 S0213-9111(06)02000100009
                10.1157/13084128
                70fbbd3d-bafd-4cd4-93ef-457b17ed1793

                This work is licensed under a Creative Commons Attribution-NonCommercial 3.0 International License.

                History
                : 18 May 2005
                : 29 September 2005
                Page count
                Figures: 0, Tables: 0, Equations: 0, References: 11, Pages: 4
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                SciELO Public Health

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                Ácido acetilsalicílico,Esomeprazol,Clopidogrel,Análisis coste-efectividad,Hemorragia gastrointestinal,Prevención de eventos cardiovasculares,Omeprazol,Aspirin,Esomeprazole,Cost-effectiveness analysis,Gastrointestinal bleeding,Cardiovascular events prevention,Omeprazole

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