RESUMEN
Dual antiplatelet therapy (DAPT) use is the standard of practice after flow diversion (FD) for intracranial aneurysms (IAs). Yet, no consensus exists in the literature regarding the optimal regimen. Certain institutions utilize various platelet function testing (PFT) to assess patient responsiveness to DAPT. Clopidogrel is the most commonly prescribed drug during DAPT; however, up to 52% of patients can be non-responders, justifying PFT use. Additionally, prices vary significantly among antiplatelet drugs, often further complicated by insurance restrictions. We aimed to determine the most cost-effective strategy for deciding DAPT regimens for patients after IA treatment. A decision tree with Monte Carlo simulations was performed to simulate patients undergoing various three-month postoperative DAPT regimens. Patients were either universally administered aspirin alongside clopidogrel, ticagrelor, or prasugrel without PFT, or administered one of the former thienopyridine medications based on platelet reactivity unit (PRU) results after clopidogrel. Input data for the model were extracted from the current literature, and the willingness-to-pay threshold (WTP) was defined as $100,000 per QALY as per standard practice in the US. The baseline comparison was with universal clopidogrel DAPT without any PFT. Probabilistic and deterministic sensitivity analyses were performed to evaluate the robustness of the model. Utilizing PFT and switching clopidogrel to prasugrel if resistance is documented was the most cost-effective regimen compared to universal clopidogrel, with a base-case incremental cost-effectiveness ratio (ICER) of $-35,255 (cost $2,336.67, effectiveness 0.85). Performing PFT and switching clopidogrel to ticagrelor (ICER $-4,671; cost $2,995.06, effectiveness 0.84), universal prasugrel (ICER $5,553; cost $3,097.30, effectiveness 0.84), or universal ticagrelor (ICER $75,969; cost $3,801.36, effectiveness 0.84) were all more cost-effective than treating patients with universal clopidogrel (cost $3,041.77, effectiveness 0.83). These conclusions remain robust in probabilistic and deterministic sensitivity analyses. The most cost-effective strategy guiding DAPT after FD for IAs is to perform PFTs and switch clopidogrel to prasugrel if resistance is documented, alongside aspirin. The cost of PFT is strongly justified and recommended when deciding patient-specific DAPT regimens.
Asunto(s)
Análisis Costo-Beneficio , Aneurisma Intracraneal , Inhibidores de Agregación Plaquetaria , Pruebas de Función Plaquetaria , Humanos , Aneurisma Intracraneal/cirugía , Aneurisma Intracraneal/tratamiento farmacológico , Inhibidores de Agregación Plaquetaria/uso terapéutico , Inhibidores de Agregación Plaquetaria/economía , Clopidogrel/uso terapéutico , Clopidogrel/economía , Clorhidrato de Prasugrel/uso terapéutico , Clorhidrato de Prasugrel/economía , Aspirina/uso terapéutico , Aspirina/economía , Ticagrelor/uso terapéutico , Terapia Antiplaquetaria Doble/métodosRESUMEN
We evaluated the cost-effectiveness of a genotype-guided strategy among patients with acute coronary syndromes using a decision-tree model based on the Singapore healthcare payer's perspective over a 1-year time horizon. Three dual antiplatelet strategies were considered: universal clopidogrel, genotype-guided, and universal ticagrelor. The prevalence of loss-of-function alleles was assumed to be 61.7% and model inputs were identified from the literature. Our primary outcome of interest was incremental cost-effectiveness ratio (ICER) compared to universal clopidogrel. Both genotype-guided (72,158 SGD/QALY) and universal ticagrelor (82,269 SGD/QALY) were considered cost-effective based on a willingness-to-pay (WTP) threshold of SGD 88,991. In our secondary analysis, the ICER for universal ticagrelor was 114,998 SGD/QALY when genotype-guided was taken as a reference. Probabilistic sensitivity analysis revealed that genotype-guided was the most cost-effective strategy when the WTP threshold was between SGD 70,000 to 100,000. Until more data are available, our study suggests that funding for a once-off CYP2C19 testing merits a consideration over 1 year of universal ticagrelor.
Asunto(s)
Síndrome Coronario Agudo/tratamiento farmacológico , Síndrome Coronario Agudo/genética , Citocromo P-450 CYP2C19/genética , Inhibidores de Agregación Plaquetaria/economía , Inhibidores de Agregación Plaquetaria/uso terapéutico , Síndrome Coronario Agudo/economía , Clopidogrel/economía , Clopidogrel/uso terapéutico , Análisis Costo-Beneficio/economía , Costos de los Medicamentos , Genotipo , Humanos , Años de Vida Ajustados por Calidad de Vida , Singapur , Ticagrelor/economía , Ticagrelor/uso terapéutico , Ticlopidina/economía , Ticlopidina/uso terapéuticoRESUMEN
BACKGROUND AND OBJECTIVES: Clopidogrel is widely used after the percutaneous coronary intervention (PCI) in patients with acute coronary syndrome (ACS) and requires activation by cytochrome P450 (CYP), primarily CYP2C19. Patients with CYP2C19 loss-of-function alleles are at increased risk of major adverse cardiovascular events, while more expensive novel antiplatelet agents (ticagrelor and prasugrel) are unaffected by the CYP2C19 mutations. This systematic review aims to answer the question about whether overall evidence supports the genotype-guided selection of antiplatelet therapy as a cost-effective strategy in post-PCI ACS. METHODS: A systematic literature search of PubMed, EMBASE, EconLit, and PharmGKB was done to identify all the economic evaluations related to genotype-guided therapy compared to the universal use of antiplatelets in ACS patients. Quality of Health Economic Studies tool was used for quality assessment. RESULTS: The search identified 13 articles, where genotype-guided treatment was compared to universal clopidogrel, ticagrelor, and/or prasugrel. Six studies showed that genotype-guided therapy was cost-effective compared to universal clopidogrel, while 5 studies showed that it was dominant. One study specified that genotype-guided with ticagrelor is cost-effective only in both CYP2C19 intermediate and poor metabolizers. Genotype-guided therapy was dominant when compared to universal prasugrel, ticagrelor, or both in 5, 1, and 3 studies, respectively. Only 2 studies reported that universal ticagrelor was cost-effective compared to genotype-guided treatment. All the included articles had good quality. CONCLUSION: Based on current economic evaluations in the literature, implementing CYP2C19 genotype-guided therapy is a cost-effective approach in guiding the selection of medication in patients with ACS undergoing PCI.
Asunto(s)
Síndrome Coronario Agudo/tratamiento farmacológico , Síndrome Coronario Agudo/economía , Citocromo P-450 CYP2C19/genética , Costos de los Medicamentos , Pruebas de Farmacogenómica/economía , Variantes Farmacogenómicas , Inhibidores de Agregación Plaquetaria/economía , Inhibidores de Agregación Plaquetaria/uso terapéutico , Medicina de Precisión/economía , Síndrome Coronario Agudo/sangre , Síndrome Coronario Agudo/diagnóstico , Toma de Decisiones Clínicas , Clopidogrel/economía , Clopidogrel/uso terapéutico , Citocromo P-450 CYP2C19/metabolismo , Humanos , Selección de Paciente , Inhibidores de Agregación Plaquetaria/efectos adversos , Inhibidores de Agregación Plaquetaria/farmacocinética , Clorhidrato de Prasugrel/economía , Clorhidrato de Prasugrel/uso terapéutico , Valor Predictivo de las Pruebas , Ticagrelor/economía , Ticagrelor/uso terapéutico , Resultado del TratamientoRESUMEN
Current guidelines recommend dual antiplatelet therapy (DAPT) consisting of aspirin and a P2Y12 inhibitors following percutaneous coronary intervention (PCI). CYP2C19 genotype can guide DAPT selection, prescribing ticagrelor or prasugrel for loss-of-function (LOF) allele carriers (genotype-guided escalation). Cost-effectiveness analyses (CEA) are traditionally grounded in clinical trial data. We conduct a CEA using real-world data using a 1-year decision-analytic model comparing primary strategies: universal empiric clopidogrel (base case), universal ticagrelor, and genotype-guided escalation. We also explore secondary strategies commonly implemented in practice, wherein all patients are prescribed ticagrelor for 30 days post PCI. After 30 days, all patients are switched to clopidogrel irrespective of genotype (nonguided de-escalation) or to clopidogrel only if patients do not harbor an LOF allele (genotype-guided de-escalation). Compared with universal clopidogrel, both universal ticagrelor and genotype-guided escalation were superior with improvement in quality-adjusted life years (QALY's). Only genotype-guided escalation was cost-effective ($42,365/QALY) and demonstrated the highest probability of being cost-effective across conventional willingness-to-pay thresholds. In the secondary analysis, compared with the nonguided de-escalation strategy, although genotype-guided de-escalation and universal ticagrelor were more effective, with ICER of $188,680/QALY and $678,215/QALY, respectively, they were not cost-effective. CYP2C19 genotype-guided antiplatelet prescribing is cost-effective compared with either universal clopidogrel or universal ticagrelor using real-world implementation data. The secondary analysis suggests genotype-guided and nonguided de-escalation may be viable strategies, needing further evaluation.
Asunto(s)
Síndrome Coronario Agudo/economía , Síndrome Coronario Agudo/terapia , Citocromo P-450 CYP2C19/genética , Costos de los Medicamentos , Técnicas de Diagnóstico Molecular/economía , Intervención Coronaria Percutánea , Variantes Farmacogenómicas , Inhibidores de Agregación Plaquetaria/economía , Inhibidores de Agregación Plaquetaria/uso terapéutico , Síndrome Coronario Agudo/genética , Aspirina/economía , Aspirina/uso terapéutico , Clopidogrel/economía , Clopidogrel/uso terapéutico , Análisis Costo-Beneficio , Técnicas de Apoyo para la Decisión , Terapia Antiplaquetaria Doble/economía , Humanos , Intervención Coronaria Percutánea/efectos adversos , Inhibidores de Agregación Plaquetaria/efectos adversos , Valor Predictivo de las Pruebas , Años de Vida Ajustados por Calidad de Vida , Ticagrelor/economía , Ticagrelor/uso terapéutico , Factores de Tiempo , Resultado del TratamientoRESUMEN
OBJETIVO: Evaluar la persistencia al tratamiento y el uso de los recursos y sus costes en sujetos que inician tratamiento con clopidogrel de marca frente a genérico para el síndrome coronario agudo (SCA) y la enfermedad arterial periférica (EAP). PACIENTES Y MÉTODOS: Estudio observacional-retrospectivo, realizado a partir de los registros médicos de pacientes ≥18 años, que iniciaron un nuevo tratamiento con clopidogrel (marca vs. genérico) entre el 1 de abril de 2015 y el 31 de marzo de 2017. Se compararon 4 grupos de estudio y el seguimiento fue de un año. Principales medidas: comorbilidad, persistencia al tratamiento, ratio posesión-medicación (RPM) y uso de recursos y costes. Los resultados se analizaron mediante análisis multivariante, p < 0,05. RESULTADOS: Se compararon 4 grupos: a) SCA: clopidogrel-marca (n=1.067) vs. genérico (n=3.504); y b) EAP: clopidogrel-marca (n=425) vs. genérico (n=994). Para el SCA (edad media: 69,7 años; 61,4% hombres), con clopidogrel de marca, la persistencia (65,3% vs. 61,0%; p < 0,001); hazard-ratio ajustado 0,85 y el RPM (89,8% vs. 86,7%; p = 0,045) fueron superiores al genérico. El promedio/unitario del coste fue menor (2.890 vs. 3.865, p = 0,001).Para la EAP se observaron resultados similares con clopidogrel de marca, la persistencia (64,7% vs. 58,9%; p = 0,039), hazard-ratio ajustado 0,86 y el RPM (88,6% vs. 81,7%; p = 0,013) fueron superiores al genérico. El promedio/unitario del coste fue menor (2.880 vs. 3.532, p = 0,044). CONCLUSIONES: Los pacientes que inician tratamiento con clopidogrel de marca vs. genérico, tanto para el SCA como para el EAP, se asociaron a un mayor grado de adherencia al tratamiento, repercutiendo en unos menores costes sanitarios para el Sistema Nacional de Salud
OBJECTIVE: To evaluate the adherence to treatment, resource use, and costs in subjects initiating treatment with brand-name versus generic clopidogrel for acute coronary syndrome (ACS) and peripheral arterial disease (PAD). PATIENTS AND METHODS: Observational, retrospective study based on the medical records of patients aged ≥18 years who initiated treatment with clopidogrel (brand-name vs. generic) between 4 April 2015 and 31 March 2017. Four study groups were compared, and the follow-up was one year. The main measurements were: comorbidity, treatment adherence, medication possession ratio (MPR), resource use, and costs. The results were analysed using multivariate analysis. The level of statistical significance was P<.05. RESULTS: Four groups were compared: a) ACS: brand-name clopidogrel (N=1,067) vs. generic (N=3,504), and b) PAD: brand-name clopidogrel (N=425) vs. generic (N=994). In the ACS comparison (mean age: 69.7 years, 61.4% male), adherence (65.3% vs. 61.0%, P<.001), adjusted hazard ratio 0.85 and MPR (89.8% vs. 86.7%, P=.045) were more superior with brand-name clopidogrel than with the generic and with a lower mean cost per unit (2,890 vs. 3,865, P=.001). In the PAD comparison, similar results were observed: persistence (64.7% vs. 58.9%, P=.039); adjusted hazard-ratio 0.86 and MPR (88.6% vs. 81.7%; P=.013) were more superior with brand-name clopidogrel than for the generic, with a lower mean cost per unit (2,880 vs. 3,532, P=.044). CONCLUSIONS: There was better treatment adherence in patients initiating treatment with brand-name compared with generic clopidogrel for ACS and PAD, resulting in lower health costs for the Spanish National Health System
Asunto(s)
Humanos , Masculino , Femenino , Adolescente , Adulto Joven , Adulto , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Síndrome Coronario Agudo/tratamiento farmacológico , Clopidogrel/administración & dosificación , Medicamentos Genéricos/administración & dosificación , Enfermedad Arterial Periférica/tratamiento farmacológico , Síndrome Coronario Agudo/economía , Clopidogrel/economía , Medicamentos Genéricos/economía , Costos de la Atención en Salud , Cumplimiento de la Medicación/estadística & datos numéricos , Enfermedad Arterial Periférica/economía , Inhibidores de Agregación Plaquetaria/administración & dosificación , Inhibidores de Agregación Plaquetaria/economía , Estudios Retrospectivos , EspañaRESUMEN
Objective: To assess the cost-effectiveness of clopidogrel versus aspirin for high risk patients (pre-existing symptomatic atherosclerosis or multi-vascular territory involvement) with established peripheral arterial disease (PAD) for secondary prevention of atherothrombotic events in a Chinese setting.Methods: A Markov model with a lifetime horizon was developed from the perspective of the national healthcare system in China. The primary outputs are quality adjusted life years (QALYs), direct medical costs, and the incremental cost-effectiveness ratios (ICERs). Clinical efficacy data were obtained from the CAPRIE trial. Drug acquisition cost, other direct medical costs, and utilities were from pricing records and the literature. One-way sensitivity analysis and probabilistic sensitivity analysis (PSA) were conducted to test the robustness of the model on all parameters.Results: In patients with pre-existing atherosclerosis, 2 years of treatment with clopidogrel and aspirin would yield total QALYs of 8.776 and 8.576 at associated costs of ¥18,777 ($2,838) and ¥12,302 ($1,859), respectively, resulting in an ICER of ¥32,382 ($4,893) per QALY gained. In patients with PVD, secondary prevention with the same drugs would expect to lead to total QALYs of 8.836 and 8.632 at associated costs of ¥18,518 ($2,798) and ¥12,041 ($1,820), respectively, resulting in a corresponding ICER of ¥31,743 ($4,797) per QALY gained. The results were most sensitive to the discount rate for future outcomes and costs. The PSA indicated that the probability of clopidogrel being cost-effective was 100% at the willingness-to-pay threshold of 3-times GDP.Conclusions: Secondary prevention with clopidogrel is an attractive cost-effective option compared with aspirin for high risk patients with established PAD from the perspective of the national healthcare system in Chinese settings.
Asunto(s)
Aspirina/economía , Clopidogrel/economía , Enfermedad Arterial Periférica/complicaciones , Inhibidores de Agregación Plaquetaria/economía , Prevención Secundaria/economía , Aspirina/administración & dosificación , Clopidogrel/administración & dosificación , Análisis Costo-Beneficio , Gastos en Salud , Humanos , Cadenas de Markov , Modelos Econométricos , Inhibidores de Agregación Plaquetaria/administración & dosificación , Años de Vida Ajustados por Calidad de Vida , Prevención Secundaria/métodos , Trombosis/etiología , Trombosis/prevención & controlRESUMEN
OBJECTIVE: To evaluate the adherence to treatment, resource use, and costs in subjects initiating treatment with brand-name versus generic clopidogrel for acute coronary syndrome (ACS) and peripheral arterial disease (PAD). PATIENTS AND METHODS: Observational, retrospective study based on the medical records of patients aged ≥18 years who initiated treatment with clopidogrel (brand-name vs. generic) between 4 April 2015 and 31 March 2017. Four study groups were compared, and the follow-up was one year. The main measurements were: comorbidity, treatment adherence, medication possession ratio (MPR), resource use, and costs. The results were analysed using multivariate analysis. The level of statistical significance was P<.05. RESULTS: Four groups were compared: a) ACS: brand-name clopidogrel (N=1,067) vs. generic (N=3,504), and b) PAD: brand-name clopidogrel (N=425) vs. generic (N=994). In the ACS comparison (mean age: 69.7 years, 61.4% male), adherence (65.3% vs. 61.0%, P<.001), adjusted hazard ratio 0.85 and MPR (89.8% vs. 86.7%, P=.045) were more superior with brand-name clopidogrel than with the generic and with a lower mean cost per unit (2,890 vs. 3,865, P=.001). In the PAD comparison, similar results were observed: persistence (64.7% vs. 58.9%, P=.039); adjusted hazard-ratio 0.86 and MPR (88.6% vs. 81.7%; P=.013) were more superior with brand-name clopidogrel than for the generic, with a lower mean cost per unit (2,880 vs. 3,532, P=.044). CONCLUSIONS: There was better treatment adherence in patients initiating treatment with brand-name compared with generic clopidogrel for ACS and PAD, resulting in lower health costs for the Spanish National Health System.
Asunto(s)
Síndrome Coronario Agudo/tratamiento farmacológico , Clopidogrel/administración & dosificación , Medicamentos Genéricos/administración & dosificación , Enfermedad Arterial Periférica/tratamiento farmacológico , Síndrome Coronario Agudo/economía , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Clopidogrel/economía , Medicamentos Genéricos/economía , Femenino , Costos de la Atención en Salud , Humanos , Masculino , Cumplimiento de la Medicación/estadística & datos numéricos , Persona de Mediana Edad , Enfermedad Arterial Periférica/economía , Inhibidores de Agregación Plaquetaria/administración & dosificación , Inhibidores de Agregación Plaquetaria/economía , Estudios Retrospectivos , España , Adulto JovenRESUMEN
Aim: This study aimed to evaluate the cost-effectiveness of CYP2C19 loss-of-function(LOF) allele-guided antiplatelet therapy compared with the universal use of clopidogrel or ticagrelor among Chinese patients with acute coronary syndrome undergoing percutaneous coronary intervention. Methods: A two-part cost-effectiveness model comprising of a 1-year decision tree and a long-term Markov model was utilized to simulate outcomes of three treatment strategies: universal use of clopidogrel (75 mg daily) or universal use of ticagrelor 90 mg twice daily for all patients and CYP2C19 LOF-guided therapy (LOF allele carriers receiving ticagrelor, LOF allele noncarriers receiving clopidogrel). Model outcomes included quality-adjusted life years (QALYs) gained, direct medical costs and incremental cost-effectiveness ratios (ICERs). ICERs less than one-time gross domestic product per capita in China 59,660 yuan/QALY were considered cost-effective. Results: Base-case analysis showed 'universal ticagrelor use' was cost-effective for an ICER of 33,875 yuan per QALY gained compared with 'universal clopidogrel use' of which gained a 1.6932 QALYs at lowest life-long cost of 2450 yuan. CYP2C19 LOF-guided therapy had an effectiveness of 1.6975 QALYs at a cost of 2812 yuan, for an ICER of 84,118 yuan per QALY gained relative to 'universal clopidogrel use'. Sensitivity analysis demonstrated that base-case results were significantly affected by five factors: the risk ratio of 'non-fatal myocardial infarction', 'non-fatal stroke' and 'cardiovascular death' in ticagrelor versus clopidogrel and the annual costs of clopidogrel and ticagrelor. According to the results of Monte Carlo simulation, when willing to pay is about 32,000 yuan, patients willing to receive clopidogrel or ticagrelor are approximately equal. Conclusion: Optimal antiplatelet treatment is affected by lots of factors. The results of our study demonstrated that 'universal ticagrelor use' was cost-effective compared with 'universal clopidogrel use' for Chinese acute coronary syndrome patients with percutaneous coronary intervention.
Asunto(s)
Síndrome Coronario Agudo/tratamiento farmacológico , Análisis Costo-Beneficio , Citocromo P-450 CYP2C19/genética , Inhibidores de Agregación Plaquetaria/administración & dosificación , Síndrome Coronario Agudo/economía , Síndrome Coronario Agudo/genética , Síndrome Coronario Agudo/patología , China/epidemiología , Clopidogrel/administración & dosificación , Clopidogrel/economía , Femenino , Humanos , Mutación con Pérdida de Función/genética , Masculino , Persona de Mediana Edad , Inhibidores de Agregación Plaquetaria/efectos adversos , Ticagrelor/administración & dosificación , Ticagrelor/economíaRESUMEN
No disponible
Asunto(s)
Humanos , Clopidogrel/uso terapéutico , Inhibidores de Agregación Plaquetaria/uso terapéutico , Medicamentos Genéricos/uso terapéutico , Medicamentos Genéricos/economía , Clopidogrel/economía , Inhibidores de Agregación Plaquetaria/economía , Síndrome Coronario Agudo/tratamiento farmacológico , Enfermedad Arterial Periférica/tratamiento farmacológico , Gastos en SaludRESUMEN
BACKGROUND: The threshold of sufficient evidence for adoption of clinically- and genomically-guided precision medicine (PM) has been unclear. OBJECTIVE: To evaluate evidence thresholds for clinically guided PM versus genomically guided PM. METHODS: We develop an "evidence threshold criterion" (ETC), which is the time-weighted difference between expected value of perfect information and incremental net health benefit minus the cost of research, and use it as a measure of evidence threshold that is proportional to the upper bound of disutility to a risk-averse decision maker for adopting a new intervention under decision uncertainty. A larger (more negative) ETC value indicates that only decision makers with low risk aversion would adopt new intervention. We evaluated the ETC plus cost of research (ETCc), assuming the same cost of research for both interventions, over time for a pharmacogenomic (PGx) testing intervention and avoidance of a drug-drug interaction (aDDI) intervention for acute coronary syndrome patients indicated for antiplatelet therapy. We then examined how the ETC may explain incongruous decision making across different national decision-making bodies. RESULTS: The ETCc for PGx increased over time, whereas the ETCc for aDDI decreased to a negative value over time, indicating that decision makers with even low risk aversion will have doubts in adopting PGx, whereas decision makers who are highly risk-averse will continue to have doubts about adopting aDDI. National recommendation bodies appear to be consistent over time within their own decision making, but had different levels of risk aversion. CONCLUSION: The ETC may be a useful metric for assessing policy makers' risk preferences and, in particular, understanding differences in policy recommendations for genomic versus clinical PM.
Asunto(s)
Pruebas de Farmacogenómica/economía , Medicina de Precisión/economía , Evaluación de la Tecnología Biomédica/métodos , Síndrome Coronario Agudo/tratamiento farmacológico , Clopidogrel/economía , Clopidogrel/uso terapéutico , Análisis Costo-Beneficio , Citocromo P-450 CYP2C19/genética , Toma de Decisiones , Interacciones Farmacológicas , Humanos , Modelos Económicos , Pruebas de Farmacogenómica/métodos , Inhibidores de Agregación Plaquetaria/economía , Inhibidores de Agregación Plaquetaria/uso terapéutico , Clorhidrato de Prasugrel/economía , Clorhidrato de Prasugrel/uso terapéutico , Medicina de Precisión/métodos , Inhibidores de la Bomba de Protones/farmacología , Años de Vida Ajustados por Calidad de Vida , Medición de Riesgo , Ticagrelor/economía , Ticagrelor/uso terapéutico , IncertidumbreRESUMEN
BACKGROUND: Clopidogrel has been widely used to prevent atherothrombotic events. Since 2011, pharmacists have offered their patients the opportunity to switch to generic clopidogrel, an economic alternative. Whether bioequivalence of generic cardiovascular drugs translates into clinical equivalence at a population level remains unclear and needs to be further documented. OBJECTIVE: We aimed to evaluate the impact of generic clopidogrel commercialization on adverse events (AEs): hospitalizations or emergency room (ER) consultations. METHODS: This is an interrupted time series analysis using the Quebec Integrated Chronic Disease Surveillance System. We included all patients ≥ 66 years old who were users of the brand-name clopidogrel or a generic version (n = 6) 24 months before and up to 12 months after generics commercialization. Rates of AEs were computed, and periods before and after generics commercialization were analyzed by segmented regression models along with exploratory analyses (generic vs. brand name). Sensitivity analyses were also performed using stratification of the time series by (1) sex, (2) the number of prevalent cardiovascular comorbidities, and (3) socioeconomic status. RESULTS: Time series were constituted of 89,525 clopidogrel users (mean age 78 years, 45% women, 71% ischemic heart disease, 34% stroke). For all users, there was a mean rate of 157 AEs per 1000 user-months, stable trend before (-0.1% [95% confidence interval -0.3 to 0.1] and after (0.0% [- 0.5 to 0.6]) generics commercialization. In exploratory analyses, once generic clopidogrel versions were commercialized, rates of AEs were 19.2% (95% CI 11.7-26.7) higher for generic versus brand-name users. This difference persisted up to 1 year. Sensitivity analyses yielded similar results. CONCLUSIONS: The population treated with clopidogrel had similar rates of hospitalizations or ER consultations before and after generics commercialization. However, differences in rates of hospitalizations or ER consultations between generic and brand-name clopidogrel users may represent a drug safety signal which remains to be validated. Using a different study design, permitting adjustment for potential confounders, could be useful in this regard.
Asunto(s)
Clopidogrel/uso terapéutico , Medicamentos Genéricos/uso terapéutico , Servicio de Urgencia en Hospital/tendencias , Hospitalización/tendencias , Derivación y Consulta/tendencias , Adulto , Anciano , Clopidogrel/efectos adversos , Clopidogrel/economía , Comorbilidad , Costos de los Medicamentos , Medicamentos Genéricos/efectos adversos , Medicamentos Genéricos/economía , Medicamentos Genéricos/farmacología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Quebec , Análisis de Regresión , Equivalencia Terapéutica , Resultado del TratamientoRESUMEN
BACKGROUND: Balancing ischemic and bleeding risk is an evolving framework. METHODS AND RESULTS: Our objectives were to simulate changes in risks for adverse events and event-driven costs with use of ticagrelor or prasugrel versus clopidogrel according to varying levels of ischemic and bleeding risk. Using the validated PARIS risk functions, we estimated 1-year ischemic (myocardial infarction or stent thrombosis) and bleeding (Bleeding Academic Research Consortium types 3 or 5) event rates among PARIS study participants who underwent percutaneous coronary intervention with drug-eluting stent implantation for an acute coronary syndrome and were discharged with aspirin and clopidogrel (n=1497). Simulated changes in adverse events with ticagrelor or prasugrel were calculated by applying treatment effects from randomized trials for a 1-year time horizon. Event costs were estimated using National Inpatient Sample data. Net costs were calculated between antiplatelet therapy groups according to level of ischemic and bleeding risk. After weighting events for quality-of-life impact, we calculated event rates and costs for risk-tailored treatment versus clopidogrel under multiple drug pricing assumptions. One-year rates (per 1000 person-years) for ischemic events were 12.6, 24.1, and 66.1, respectively, among those at low (n=630), intermediate (n=536), and high (n=331) ischemic risk. Analogous bleeding rates were 11.0, 23.9, and 66.2, respectively, among low (n=728), intermediate (n=634), and high (n=135) bleeding risk patients. Mean per event costs were $22 174 (ischemic) and $12 203 (bleeding). When risks for ischemia matched or exceeded bleeding, simulated utility-weighted event rates favored ticagrelor/prasugrel, whereas clopidogrel reduced utility-weighted events when bleeding exceeded ischemic risk. One-year costs were sensitive to drug pricing assumptions, and risk-tailored treatment with either agent progressed from cost incurring to cost saving with increasing generic market share. CONCLUSIONS: Tailoring antiplatelet therapy intensity to patient risk may improve health utility and could produce cost savings in the first year after percutaneous coronary intervention. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT00998127.
Asunto(s)
Síndrome Coronario Agudo/terapia , Clopidogrel/administración & dosificación , Trombosis Coronaria/prevención & control , Isquemia Miocárdica/prevención & control , Intervención Coronaria Percutánea , Inhibidores de Agregación Plaquetaria/administración & dosificación , Clorhidrato de Prasugrel/administración & dosificación , Ticagrelor/administración & dosificación , Síndrome Coronario Agudo/economía , Síndrome Coronario Agudo/epidemiología , Anciano , Anciano de 80 o más Años , Toma de Decisiones Clínicas , Clopidogrel/efectos adversos , Clopidogrel/economía , Trombosis Coronaria/economía , Trombosis Coronaria/epidemiología , Ahorro de Costo , Análisis Costo-Beneficio , Costos de los Medicamentos , Stents Liberadores de Fármacos , Europa (Continente)/epidemiología , Femenino , Hemorragia/inducido químicamente , Hemorragia/economía , Hemorragia/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Isquemia Miocárdica/economía , Isquemia Miocárdica/epidemiología , Intervención Coronaria Percutánea/efectos adversos , Intervención Coronaria Percutánea/economía , Intervención Coronaria Percutánea/instrumentación , Inhibidores de Agregación Plaquetaria/efectos adversos , Inhibidores de Agregación Plaquetaria/economía , Clorhidrato de Prasugrel/efectos adversos , Clorhidrato de Prasugrel/economía , Sistema de Registros , Medición de Riesgo , Factores de Riesgo , Ticagrelor/efectos adversos , Ticagrelor/economía , Factores de Tiempo , Resultado del Tratamiento , Estados Unidos/epidemiologíaRESUMEN
BACKGROUND: Antiplatelet agents are the cornerstone of medical treatment in acute coronary syndromes. The aim of this study was to evaluate the clinical epidemiology of patients after an acute coronary syndrome treated with different antiplatelet agent regimens in a large real community setting. METHODS: The ARCO database, including more than 12 million inhabitants, was evaluated. Antiplatelet agent prescriptions were analysed as follows: aspirin, clopidogrel, other antiplatelet agents used alone; the free and fixed combination of clopidogrel and aspirin; the free combination of aspirin with other antiplatelet agents. Healthcare costs included drug prescriptions (prices reimbursed by the Italian National Health System), outpatient specialist services and hospitalisations (Italian national tariffs). RESULTS: From 1 January to 31 December 2014, 26,834 patients were discharged after an acute coronary syndrome. Of these, 19,333 (77%) were prescribed with an antiplatelet agent. Among patients undergoing a revascularisation procedure either percutaneous or surgical (47% of the total population), antiplatelet agents were prescribed in 90% of cases. Dual antiplatelet agent therapy was prescribed in 49.6% of the total population and in 68.5% of those treated invasively. Prescription continuity was observed in just 75% of patients. The highest adherence was observed for the fixed combination of aspirin/clopidogrel (81.5%). Throughout one year of follow-up re-hospitalisation occurred in 47.9% of the patients and the direct cost per patient treated with an antiplatelet agent was 13,297 versus 16,647 in patients not treated with antiplatelet agents. CONCLUSIONS: This study highlights that antiplatelet agent prescriptions, specifically dual antiplatelet agent therapy, are at least suboptimal as well as in prescription continuity. Hospitalisations were frequent and were the main driver of the costs, accounting for 84% of the total costs for the Italian National Health System.
Asunto(s)
Síndrome Coronario Agudo/tratamiento farmacológico , Aspirina/uso terapéutico , Clopidogrel/uso terapéutico , Inhibidores de Agregación Plaquetaria/uso terapéutico , Síndrome Coronario Agudo/epidemiología , Síndrome Coronario Agudo/cirugía , Cuidados Posteriores , Anciano , Anciano de 80 o más Años , Aspirina/administración & dosificación , Aspirina/economía , Clopidogrel/administración & dosificación , Clopidogrel/economía , Bases de Datos Factuales , Quimioterapia Combinada , Femenino , Costos de la Atención en Salud/estadística & datos numéricos , Hospitalización/estadística & datos numéricos , Humanos , Italia/epidemiología , Masculino , Cumplimiento de la Medicación/estadística & datos numéricos , Persona de Mediana Edad , Alta del Paciente , Intervención Coronaria Percutánea/métodos , Inhibidores de Agregación Plaquetaria/administración & dosificación , Inhibidores de Agregación Plaquetaria/economía , Clorhidrato de Prasugrel/administración & dosificación , Clorhidrato de Prasugrel/economía , Clorhidrato de Prasugrel/uso terapéutico , Antagonistas del Receptor Purinérgico P2Y/administración & dosificación , Antagonistas del Receptor Purinérgico P2Y/economía , Antagonistas del Receptor Purinérgico P2Y/uso terapéutico , Estudios Retrospectivos , Ticagrelor/administración & dosificación , Ticagrelor/economía , Ticagrelor/uso terapéuticoRESUMEN
PURPOSE: Monotherapy with either aspirin or clopidogrel is recommended for long-term use after discontinuation of dual-antiplatelet therapy (DAPT) for acute coronary syndrome (ACS) management after percutaneous coronary intervention (PCI). The present study is to evaluate the cost-effectiveness of clopidogrel versus aspirin after 12-month DAPT for patients with ACS who underwent PCI in China. METHODS: A 2-part model was developed to estimate the cost-effectiveness of clopidogrel compared with aspirin. The short-term part was a decision tree that included health states such as myocardial infarction (MI), stroke, MI and stroke, cardiovascular death, and death from other causes with a treatment horizon of 1 year (base case), 2 years or 3 years after 12-month DAPT. Major bleeding was included. The long-term (lifetime) part was a Markov model that included different health states such as MI, after MI, stroke, after stroke, and death. Drug acquisition cost and other direct medical costs were based on pricing records, literature, and expert panels. Clinical outcomes and utilities were based on literature. The model output included incremental cost-effectiveness ratio of quality-adjusted life-years (QALYs) and total costs per patient. Both 1-way sensitivity analysis and probabilistic sensitivity analysis (PSA) were conducted. FINDINGS: In the base-case scenario, the total costs of the treatment with clopidogrel and aspirin were ¥12,590 ($1849/1590) and ¥10,642 ($1563/1344), respectively; the total QALYs of the 2 patient populations were 9.7341 and 9.6894, respectively. The incremental cost-effectiveness ratio of ¥43,593 ($6402/5515) per QALY gained was lower than 3 times of gross domestic product (GDP) per capita in China (¥161,940, $23,786/20,449). Both 1-way sensitivity analysis and PSA confirmed the robustness of the results. PSA results indicated that clopidogrel was cost effective versus aspirin in 80.5% of the simulations, considering >3 times the GDP per capita as the threshold. Results in other scenarios (clopidogrel or aspirin for 2 or 3 years after 12-month DAPT) also indicated that clopidogrel was more cost effective than aspirin for patients with ACS after 12-month DAPT. IMPLICATIONS: Compared with aspirin monotherapy, clopidogrel monotherapy for 1 year after 12-month DAPT was cost effective for patients with ACS who underwent PCI in China. Furthermore, when the duration of clopidogrel the monotherapy extended up to 3 years, clopidogrel was still cost effective compared with aspirin. The study was limited by lack of high-quality efficacy data among the Chinese population.
Asunto(s)
Síndrome Coronario Agudo/tratamiento farmacológico , Aspirina/uso terapéutico , Clopidogrel/uso terapéutico , Inhibidores de Agregación Plaquetaria/uso terapéutico , Síndrome Coronario Agudo/economía , Anciano , Anciano de 80 o más Años , Aspirina/economía , China , Clopidogrel/economía , Análisis Costo-Beneficio , Árboles de Decisión , Femenino , Humanos , Reembolso de Seguro de Salud , Masculino , Cadenas de Markov , Intervención Coronaria Percutánea , Inhibidores de Agregación Plaquetaria/economía , Años de Vida Ajustados por Calidad de VidaRESUMEN
BACKGROUND: Although switching between ticagrelor and clopidogrel is common in clinical practice, the efficacy and safety of this de-escalation remain controversial. HYPOTHESIS: We assessed the occurrences, reasons, and outcomes of switching from ticagrelor to clopidogrel in patients with ST-segment elevation myocardial infarction (STEMI) undergoing successful primary percutaneous coronary intervention (PCI). METHODS: A total of 653 patients with STEMI were randomly assigned to receive loading dose of ticagrelor or clopidogrel before PCI and then received maintenance dose, respectively, for 12 months follow-up. The primary outcome was major adverse cardiac events (MACE), including cardiovascular death, nonfatal myocardial infarction, and stroke. The secondary outcome included unexpected rehospitalization for angina, coronary revascularization, and stent thrombosis. The safety outcome was bleeding described by the Bleeding Academic Research Consortium (BARC) criteria. RESULTS: A total of 602 participants completed the study. The rate of switching from ticagrelor to clopidogrel was 48.6% and the main reason was financial burden. The rate of secondary ischemic events in the de-escalation group was higher than that in the ticagrelor group (15.1% vs 5.6%, P = 0.008), but lower than that in the clopidogrel group (15.1% vs 24.6%, P = 0.03), while there were no significant differences in MACE among the three groups (P = 0.16). De-escalation, ticagrelor, and clopidogrel did not cause significant differences in the rates of major bleeding among the three groups (BARC ≥ 2, P = 0.34). CONCLUSION: Switching from ticagrelor to clopidogrel is very common in patients with STEMI in China. De-escalation might be safe but associated with high risk of ischemic events as compared to ticagrelor.
Asunto(s)
Clopidogrel/administración & dosificación , Sustitución de Medicamentos , Intervención Coronaria Percutánea , Inhibidores de Agregación Plaquetaria/administración & dosificación , Infarto del Miocardio con Elevación del ST/cirugía , Ticagrelor/administración & dosificación , Anciano , China , Clopidogrel/efectos adversos , Clopidogrel/economía , Trombosis Coronaria/etiología , Trombosis Coronaria/terapia , Costos de los Medicamentos , Sustitución de Medicamentos/efectos adversos , Sustitución de Medicamentos/mortalidad , Femenino , Hemorragia/inducido químicamente , Humanos , Masculino , Persona de Mediana Edad , Readmisión del Paciente , Intervención Coronaria Percutánea/efectos adversos , Intervención Coronaria Percutánea/mortalidad , Inhibidores de Agregación Plaquetaria/efectos adversos , Estudios Prospectivos , Recurrencia , Factores de Riesgo , Infarto del Miocardio con Elevación del ST/sangre , Infarto del Miocardio con Elevación del ST/economía , Infarto del Miocardio con Elevación del ST/mortalidad , Accidente Cerebrovascular/etiología , Accidente Cerebrovascular/mortalidad , Ticagrelor/efectos adversos , Ticagrelor/economía , Factores de Tiempo , Resultado del TratamientoRESUMEN
AIM: Antiplatelets have been used for decades to prevent atherothrombotic disease, but there is limited 'real-life' prescribing data. We hereby report the prescribing patterns for oral antiplatelets in Wales, UK. METHODS/RESULTS: Retrospective analysis of anonymized data in Wales from 2005 to 2016 revealed differences in prescribing patterns of oral antiplatelets. Aspirin and dipyridamole use declined with a corresponding increase in clopidogrel prescription. Costs declined with a sharp decrease coinciding with clopidogrel coming off patent. Prasugrel and ticagrelor have shown significant cost contribution (29% of total) despite only forming 1% of total items prescribed in 2016. CONCLUSION: This first-look analysis of real-life antiplatelet data demonstrates a decrease in the overall prescribing costs with varying patterns. This may aid policy-makers in reviewing funding strategies.
Asunto(s)
Inhibidores de Agregación Plaquetaria/uso terapéutico , Pautas de la Práctica en Medicina/estadística & datos numéricos , Administración Oral , Aspirina/economía , Aspirina/uso terapéutico , Clopidogrel/economía , Clopidogrel/uso terapéutico , Dipiridamol/economía , Dipiridamol/uso terapéutico , Humanos , Inhibidores de Agregación Plaquetaria/economía , Clorhidrato de Prasugrel/economía , Clorhidrato de Prasugrel/uso terapéutico , Estudios Retrospectivos , Ticagrelor/economía , Ticagrelor/uso terapéutico , GalesRESUMEN
BACKGROUND: Despite improvements in percutaneous coronary intervention (PCI), intraprocedural thrombotic events (IPTE) and bleeding complications occur and are prognostically important. These have not been included in prior economic studies. METHODS: PHOENIX ECONOMICS was a substudy of the CHAMPION PHOENIX trial, evaluating cangrelor during PCI. Hospital bills were reviewed from 1,171 patients enrolled at 22 of 63 US sites. Costs were estimated using standard methods including resource-based accounting, hospital billing data, and the Medicare fee schedule. Bleeding and IPTE, defined as abrupt vessel closure (transient or sustained), new/suspected thrombus, new clot on wire/catheter, no reflow, side-branch occlusion, procedural stent thrombosis or urgent need for CABG were identified. Costs were calculated according to whether a complication occurred and type of event. Multivariate analyses were used to estimate the incremental costs of IPTE and postprocedural events. RESULTS: IPTE occurred in 4.3% and were associated with higher catheterization laboratory and overall index hospitalization costs by $2,734 (95%CI $1,117, $4,351; P = 0.001) and $6,354 (95% CI $4,122, $8,586; P < 0.001), respectively. IPTE were associated with MI (35.4% vs. 3.6%; P < 0.001), out-of-laboratory stent thrombosis (4.2% vs. 0.1%; 0 = 0.005), ischemia driven revascularization (12.5% vs. 0.3%; P < 0.001), but not mortality (2.1% vs. 0.2%; P = 0.12) vs. no procedural thrombotic complication. By comparison, ACUITY minor bleeding increased hospitalization cost by $1,416 (95%CI = 312, $2,519; P = 0.012). ACUITY major bleeding increased cost of hospitalization by $7,894 (95%CI $4,154, $11,635; P < 0.001). CONCLUSIONS: IPTE and bleeding complications, though infrequent, are associated with substantial increased cost. These complications should be collected in economic assessments of PCI.
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Trombosis Coronaria/economía , Trombosis Coronaria/terapia , Costos de los Medicamentos , Hemorragia/economía , Hemorragia/terapia , Costos de Hospital , Intervención Coronaria Percutánea/efectos adversos , Intervención Coronaria Percutánea/economía , Inhibidores de Agregación Plaquetaria/efectos adversos , Inhibidores de Agregación Plaquetaria/economía , Adenosina Monofosfato/efectos adversos , Adenosina Monofosfato/análogos & derivados , Adenosina Monofosfato/economía , Anciano , Clopidogrel/efectos adversos , Clopidogrel/economía , Trombosis Coronaria/etiología , Trombosis Coronaria/mortalidad , Análisis Costo-Beneficio , Método Doble Ciego , Femenino , Hemorragia/inducido químicamente , Hemorragia/mortalidad , Mortalidad Hospitalaria , Humanos , Tiempo de Internación/economía , Masculino , Persona de Mediana Edad , Modelos Económicos , Intervención Coronaria Percutánea/mortalidad , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento , Estados UnidosRESUMEN
BACKGROUND: Clopidogrel is one of the most commonly prescribed medications because of its ability to improve clinical outcomes for a broad range of cardiovascular conditions. After patent protection expired for Plavix in 2012, many healthcare systems adopted generic clopidogrel as a strategy to reduce healthcare costs. METHODS AND RESULTS: We conducted a population-based observational study to determine whether generic clopidogrel was noninferior to Plavix. Patients who were hospitalized with an acute coronary syndrome (ACS) from 2009 to 2014 in Ontario, Canada, >65 years, survived ≥7 days after discharge, were eligible for inclusion. The primary outcome was a composite of death and recurrent ACS at 1 year. The noninferiority margin was prespecified at a relative hazard difference of 10%. Inverse propensity of treatment weighting of the propensity score was used to account for differences in baseline characteristics between the treatment groups. The effect of clopidogrel on the hazard of clinical outcomes was estimated using a Cox proportional hazards model within the propensity-weighted cohort using Plavix as a reference. Our study included 24 530 patients with ACS, 12 643 were prescribed Plavix and 11 887 were prescribed generic clopidogrel at hospital discharge. The mean age was 77 years, 57% were men, and 21% had an ST-segment-elevation myocardial infarction. At 1 year, 17.6% of patients prescribed Plavix and 17.9% of patients prescribed clopidogrel experienced the primary outcome (hazard ratio, 1.02; 95% confidence interval, 0.96-1.08; P=0.005 for noninferiority). No significant differences between rates of death, all-cause readmission, ACS, stroke or transient ischemic attack, or bleeding were observed. CONCLUSIONS: Generic clopidogrel was noninferior to Plavix with respect to the composite end point of death and recurrent hospitalization for ACS at 1 year among adults >65 years after an ACS hospitalization. Our findings support generic clopidogrel in ACS, which could lead to substantial healthcare cost savings.
Asunto(s)
Síndrome Coronario Agudo/tratamiento farmacológico , Clopidogrel/uso terapéutico , Medicamentos Genéricos/uso terapéutico , Admisión del Paciente , Inhibidores de Agregación Plaquetaria/uso terapéutico , Antagonistas del Receptor Purinérgico P2Y/uso terapéutico , Síndrome Coronario Agudo/sangre , Síndrome Coronario Agudo/economía , Síndrome Coronario Agudo/mortalidad , Anciano , Anciano de 80 o más Años , Clopidogrel/efectos adversos , Clopidogrel/economía , Ahorro de Costo , Análisis Costo-Beneficio , Bases de Datos Factuales , Costos de los Medicamentos , Sustitución de Medicamentos/economía , Medicamentos Genéricos/efectos adversos , Medicamentos Genéricos/economía , Femenino , Hemorragia/inducido químicamente , Humanos , Masculino , Ontario , Admisión del Paciente/economía , Readmisión del Paciente , Inhibidores de Agregación Plaquetaria/efectos adversos , Inhibidores de Agregación Plaquetaria/economía , Antagonistas del Receptor Purinérgico P2Y/economía , Recurrencia , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Resultado del TratamientoRESUMEN
Optimal antiplatelet therapy after coronary artery bypass graft (CABG) surgery remains controversial. This study evaluated the role of dual antiplatelet therapy using aspirin and clopidogrel (DAPT) versus antiplatelet therapy using aspirin only (ASA) on post-CABG clinical outcomes and costs. In the Department of Veterans Affairs Randomized On/Off Bypass (ROOBY) trial, clopidogrel use after CABG was prospectively collected beginning in year 2 of this study to include 1,525 of the 2,203 original ROOBY patients who received aspirin after CABG. Discretionarily, surgeons after CABG administered either DAPT or ASA treatments. The ROOBY trial's primary 30-day composite (mortality or perioperative morbidity), 1-year composite (all-cause death, repeat revascularization, or nonfatal myocardial infarction), and costs were compared for these 2 strategies. Of the 1,525 subjects, 511 received DAPT and 1,014 received ASA. DAPT subjects, compared with ASA subjects, had lower rates of preoperative left ventricular ejection fraction of ≥45% (78.8% vs 85.7%, p <0.001), on-pump CABG (36.6% vs 57.1%, p = 0.001), and endoscopic vein harvesting (30.0% vs 42.8%, p <0.001). ASA patients were more likely to have earlier aspirin administration and receive 325 versus 81 mg dosages. The 30-day composite outcome rate was significantly lower for DAPT patients compared with ASA patients (3.3% vs 7.1%, p = 0.003), but the 1-year composite outcome was equal between the 2 groups (12.0% vs12.0%, p = 1.0). At 1 year, there were no cost differences between the 2 groups. Propensity analyses did not significantly alter the results. In conclusion, DAPT appeared safe and was associated with fewer 30-day adverse outcomes than aspirin only and with no 1-year outcome or cost differences.