RESUMEN
BACKGROUND: The choice of antiplatelet therapy after acute coronary syndrome (ACS) is complicated: Ticagrelor and prasugrel are novel alternatives to clopidogrel, patients with some genotypes may not respond to clopidogrel, and low-cost generic formulations of clopidogrel are available. OBJECTIVE: To determine the most cost-effective strategy for dual antiplatelet therapy after percutaneous coronary intervention for ACS. DESIGN: Decision-analytic model. DATA SOURCES: Published literature, Medicare claims, and life tables. TARGET POPULATION: Patients having percutaneous coronary intervention for ACS. TIME HORIZON: Lifetime. PERSPECTIVE: Societal. INTERVENTION: Five strategies were examined: generic clopidogrel, prasugrel, ticagrelor, and genotyping for polymorphisms of CYP2C19 with carriers of loss-of-function alleles receiving either ticagrelor (genotyping with ticagrelor) or prasugrel (genotyping with prasugrel) and noncarriers receiving clopidogrel. OUTCOME MEASURES: Direct medical costs, quality-adjusted life years(QALYs), and incremental cost-effectiveness ratios (ICERs). RESULTS OF BASE-CASE ANALYSIS: The clopidogrel strategy produced$179 301 in costs and 9.428 QALYs. Genotyping with prasugrel was superior to prasugrel alone, with an ICER of $35 800 per QALY relative to clopidogrel. Genotyping with ticagrelor was more effective than genotyping with prasugrel ($30 200 per QALY relative to clopidogrel). Ticagrelor was the most effective strategy($52 600 per QALY relative to genotyping with ticagrelor). RESULTS OF SENSITIVITY ANALYSIS: Stronger associations between genotype and thrombotic outcomes rendered ticagrelor substantially less cost-effective ($104 800 per QALY). Genotyping with prasugrel was the preferred therapy among patients who could not tolerate ticagrelor. LIMITATION: No randomized trials have directly compared genotyping strategies or prasugrel with ticagrelor. CONCLUSION: Genotype-guided personalization may improve the cost-effectiveness of prasugrel and ticagrelor after percutaneous coronary intervention for ACS, but ticagrelor for all patients may bean economically reasonable alternative in some settings.
Asunto(s)
Síndrome Coronario Agudo/tratamiento farmacológico , Inhibidores de Agregación Plaquetaria/economía , Inhibidores de Agregación Plaquetaria/uso terapéutico , Síndrome Coronario Agudo/cirugía , Adenosina/efectos adversos , Adenosina/análogos & derivados , Adenosina/economía , Adenosina/uso terapéutico , Alelos , Hidrocarburo de Aril Hidroxilasas/genética , Clopidogrel , Trombosis Coronaria/prevención & control , Análisis Costo-Beneficio , Citocromo P-450 CYP2C19 , Técnicas de Apoyo para la Decisión , Costos Directos de Servicios , Quimioterapia Combinada , Medicamentos Genéricos/efectos adversos , Medicamentos Genéricos/economía , Medicamentos Genéricos/uso terapéutico , Genotipo , Hemorragia/inducido químicamente , Humanos , Intervención Coronaria Percutánea , Piperazinas/efectos adversos , Piperazinas/economía , Piperazinas/uso terapéutico , Inhibidores de Agregación Plaquetaria/efectos adversos , Polimorfismo Genético , Clorhidrato de Prasugrel , Años de Vida Ajustados por Calidad de Vida , Factores de Riesgo , Tiofenos/efectos adversos , Tiofenos/economía , Tiofenos/uso terapéutico , Ticagrelor , Ticlopidina/efectos adversos , Ticlopidina/análogos & derivados , Ticlopidina/economía , Ticlopidina/uso terapéuticoRESUMEN
PURPOSE: To evaluate the importance of angiogenesis in plaque progression after stent placement, this study examines stent-based controlled delivery of the antiangiogenic agent, angiostatin, in a rabbit model. MATERIALS AND METHODS: Controlled release biodegradable microspheres delivering angiostatin or polymer-only microspheres (polylactic-co-glycolic-acid-polyethylene glycol; PLGA/PEG) were loaded in channeled stents, anchored, and deployed in the aorta of adult New Zealand white rabbits (n = 6 animals per group, three each per time point). The stented aortas were harvested at 7 days and 28 days and evaluated for neovascularization, local inflammation, vascular smooth muscle cell proliferation, and in-stent plaque progression. RESULTS: At 7 days, neovascularization was significantly decreased in the angiostatin groups (1.6 +/- 1.6 neovessels per mm(2) plaque) versus the control group (15.4 +/- 2.6 neovessels per mm(2) plaque; P =.00081), as were local inflammation where angiostatin-treated groups demonstrated significantly lower macrophage recruitment per cross section (34.9 +/- 4.9 cells per cross section) relative to the control group (55.2 +/- 3.84 cells per cross section; P =.0037). And a significant decrease in the overall vascular smooth muscle cell proliferation (143.8 +/- 26.3 Ki-67 positive cells per mm(2)) relative to the control group (263.2 +/- 16.6 Ki-67 positive cells per mm(2); P =.00074). At both 7 and 28 days, in-stent plaque progression in the angiostatin groups was successfully limited relative to the control group by 54% (0.255 +/- 0.019% of cross section; P =.00016) and 19% (1.981 +/- 0.080; P =.0033) respectively and resulted in reduction of in-stent restenosis relative to the control group. CONCLUSION: Angiostatin-eluting stents may limit neovascularity after arterial implantation, offer insight into in-stent restenosis, and allow future refinement of bioactive stent designs and clinical strategies, particularly in light of evidence that intimal smooth muscle cells may in part be marrow-derived.