RESUMO
BACKGROUND: Genetic-guided pharmacotherapy (PGx) is not recommended in clinical guidelines for coronary artery disease (CAD). We aimed to examine the extent and quality of evidence from economic evaluations of PGx in CAD and to identify variables influential in changing conclusions on cost-effectiveness. METHODS AND RESULTS: From systematic searches across 6 databases, 2 independent reviewers screened, included, and rated the methodological quality of economic evaluations of PGx testing to guide pharmacotherapy for patients with CAD. Of 35 economic evaluations included, most were model-based cost-utility analyses alone, or alongside cost-effectiveness analyses of PGx testing to stratify patients into antiplatelets (25/35), statins (2/35), pain killers (1/35), or angiotensin-converting enzyme inhibitors (1/35) to predict CAD risk (8/35) or to determine the coumadin doses (1/35). To stratify patients into antiplatelets (96/151 comparisons with complete findings of PGx versus non-PGx), PGx was more effective and more costly than non-PGx clopidogrel (28/43) but less costly than non-PGx prasugrel (10/15) and less costly and less effective than non-PGx ticagrelor (22/25). To predict CAD risk (51/151 comparisons), PGx using genetic risk scores was more effective and less costly than clinical risk score (13/17) but more costly than no risk score (16/19) or no treatment (9/9). The remaining comparisons were too few to observe any trend. Mortality risk was the most common variable (47/294) changing conclusions. CONCLUSIONS: Economic evaluations to date found PGx to stratify patients with CAD into antiplatelets or to predict CAD risk to be cost-effective, but findings varied based on the non-PGx comparators, underscoring the importance of considering local practice in deciding whether to adopt PGx.
Assuntos
Doença da Artéria Coronariana , Análise Custo-Benefício , Inibidores da Agregação Plaquetária , Humanos , Doença da Artéria Coronariana/tratamento farmacológico , Doença da Artéria Coronariana/economia , Doença da Artéria Coronariana/genética , Inibidores da Agregação Plaquetária/uso terapêutico , Inibidores da Agregação Plaquetária/economia , Testes Farmacogenômicos/economia , Variantes Farmacogenômicos , Custos de Medicamentos , Medicina de Precisão/economia , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Inibidores de Hidroximetilglutaril-CoA Redutases/economia , Medição de RiscoRESUMO
Dual antiplatelet therapy (DAPT) with clopidogrel plus aspirin within 48 h of acute minor strokes and transient ischemic attacks (TIAs) has been indicated to effectively reduce the rate of recurrent strokes. However, the efficacy of clopidogrel has been shown to be affected by cytochrome P450 2C19 (CYP2C19) polymorphisms. Patients carrying loss-of-function alleles (LoFAs) at a low risk of recurrence (ESRS < 3) cannot benefit from clopidogrel plus aspirin at all and may have an increased bleeding risk. In order to optimize antiplatelet therapy for these patients and avoid the waste of medical resources, it is important to identify the subgroups that genuinely benefit from DAPT with clopidogrel plus aspirin through CYP2C19 genotyping. This study sought to assess the cost-effectiveness of CYP2C19 genotyping to guide drug therapy for acute minor strokes or high-risk TIAs in China. A decision tree and Markov model were constructed to evaluate the cost-effectiveness of CYP2C19 genotyping. We used a healthcare payer perspective, and the primary outcomes included quality-adjusted life years (QALYs), costs and the incremental cost-effectiveness ratio (ICER). Sensitivity analyses were performed to evaluate the robustness of the results. CYP2C19 genotyping resulted in a lifetime gain of 0.031 QALYs at an additional cost of CNY 420.13 (US$ 59.85), yielding an ICER of CNY 13,552.74 (US$ 1930.59) per QALY gained. Probabilistic sensitivity analysis showed that genetic testing was more cost-effective in 95.7% of the simulations at the willingness-to-pay threshold of CNY 72,100 (GDP per capita, US$ 10,300) per QALY. Therefore, CYP2C19 genotyping to guide antiplatelet therapy for acute minor strokes and high-risk TIAs is highly cost-effective in China.
Assuntos
Citocromo P-450 CYP2C19/genética , Ataque Isquêmico Transitório/tratamento farmacológico , Ataque Isquêmico Transitório/genética , Inibidores da Agregação Plaquetária/farmacologia , Alelos , China , Clopidogrel/farmacologia , Simulação por Computador , Análise Custo-Benefício , Árvores de Decisões , Método Duplo-Cego , Genótipo , Humanos , Ataque Isquêmico Transitório/economia , Cadeias de Markov , Neurociências , Placebos , Inibidores da Agregação Plaquetária/economia , Polimorfismo Genético , Probabilidade , Anos de Vida Ajustados por Qualidade de Vida , RiscoRESUMO
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.
Assuntos
Síndrome Coronariana Aguda/tratamento farmacológico , Síndrome Coronariana Aguda/genética , Citocromo P-450 CYP2C19/genética , Inibidores da Agregação Plaquetária/economia , Inibidores da Agregação Plaquetária/uso terapêutico , Síndrome Coronariana Aguda/economia , Clopidogrel/economia , Clopidogrel/uso terapêutico , Análise Custo-Benefício/economia , Custos de Medicamentos , Genótipo , Humanos , Anos de Vida Ajustados por Qualidade de Vida , Singapura , Ticagrelor/economia , Ticagrelor/uso terapêutico , Ticlopidina/economia , Ticlopidina/uso terapêuticoRESUMO
BACKGROUND: Acute myocardial infarction (AMI), a major source of morbidity and mortality, is also associated with excess costs. Findings from previous studies were divergent regarding the effect on health care expenditure of adherence to guideline-recommended medication. However, gender-specific medication effectiveness, correlating the effectiveness of concomitant medication and variation in adherence over time, has not yet been considered. METHODS: We aim to measure the effect of adherence on health care expenditures stratified by gender from a third-party payer's perspective in a sample of statutory insured Disease Management Program participants over a follow-up period of 3-years. In 3627 AMI patients, the proportion of days covered (PDC) for four guideline-recommended medications was calculated. A generalized additive mixed model was used, taking into account inter-individual effects (mean PDC rate) and intra-individual effects (deviation from the mean PDC rate). RESULTS: Regarding inter-individual effects, for both sexes only anti-platelet agents had a significant negative influence indicating that higher mean PDC rates lead to higher costs. With respect to intra-individual effects, for females higher deviations from the mean PDC rate for angiotensin-converting enzyme (ACE) inhibitors, anti-platelet agents, and statins were associated with higher costs. Furthermore, for males, an increasing positive deviation from the PDC mean increases costs for ß-blockers and a negative deviation decreases costs. For anti-platelet agents, an increasing deviation from the PDC-mean slightly increases costs. CONCLUSION: Positive and negative deviation from the mean PDC rate, independent of how high the mean was, usually negatively affect health care expenditures. Therefore, continuity in intake of guideline-recommended medication is important to save costs.
Assuntos
Fidelidade a Diretrizes/estatística & dados numéricos , Custos de Cuidados de Saúde/estatística & dados numéricos , Inibidores de Hidroximetilglutaril-CoA Redutases , Adesão à Medicação/estatística & dados numéricos , Infarto do Miocárdio/prevenção & controle , Inibidores da Agregação Plaquetária , Prevenção Secundária/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Continuidade da Assistência ao Paciente , Diabetes Mellitus Tipo 2 , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Inibidores de Hidroximetilglutaril-CoA Redutases/economia , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/tratamento farmacológico , Inibidores da Agregação Plaquetária/administração & dosagem , Inibidores da Agregação Plaquetária/economia , Estudos RetrospectivosRESUMO
BACKGROUND: Cost is frequently cited as a barrier to optimal medication use, but the extent to which copayment assistance interventions are used when available, and their impact on evidence-based medication persistence and major adverse cardiovascular events is unknown. METHODS AND RESULTS: The ARTEMIS trial (Affordability and Real-World Antiplatelet Treatment Effectiveness After Myocardial Infarction Study) randomized 301 hospitals to usual care versus the ability to provide patients with vouchers that offset copayment costs when filling P2Y12 inhibitors in the 1 year post-myocardial infarction. In the intervention group, we used multivariable logistic regression to identify patient and medication cost characteristics associated with voucher use. We then used this model to stratify both intervention and usual care patients by likelihood of voucher use, and examined the impact of the voucher intervention on 1-year P2Y12 inhibitor persistence (no gap in pharmacy supply >30 days) and major adverse cardiovascular events (all-cause death, myocardial infarction, or stroke). Among 10 102 enrolled patients, 6135 patients were treated at hospitals randomized to the copayment intervention. Of these, 1742 (28.4%) never used the voucher, although 1729 (99.2%) voucher never-users filled at least one P2Y12 inhibitor prescription in the 1 year post-myocardial infarction. Characteristics most associated with voucher use included: discharge on ticagrelor, planned 1-year course of P2Y12 inhibitor treatment, white race, commercial insurance, and higher out-of-pocket medication costs (c-statistic 0.74). Applying this propensity model to stratify all enrolled patients by likelihood of voucher use, the intervention improved medication persistence the most in patients with high likelihood of voucher use (adjusted interaction P=0.03, odds ratio, 1.86 [95% CI, 1.48-2.33]). The intervention did not significantly reduce major adverse cardiovascular events in any voucher use likelihood group, although the odds ratio was lowest (0.86 [95% CI, 0.56-1.16]) among patients with high likelihood of voucher use (adjusted interaction P=0.04). CONCLUSIONS: Among patients discharged after myocardial infarction, those with higher copayments and greater out-of-pocket medication costs were more likely to use a copayment assistance voucher, but some classes of patients were less likely to use a copayment assistance voucher. Patients at low likelihood of voucher use benefitted least from copayment assistance, and other interventions may be needed to improve medication-taking behaviors and clinical outcomes in these patients. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02406677.
Assuntos
Custo Compartilhado de Seguro/economia , Custos de Medicamentos , Gastos em Saúde , Adesão à Medicação , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/economia , Inibidores da Agregação Plaquetária/economia , Inibidores da Agregação Plaquetária/uso terapêutico , Antagonistas do Receptor Purinérgico P2Y/economia , Antagonistas do Receptor Purinérgico P2Y/uso terapêutico , Idoso , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/mortalidade , Fatores de Tempo , Resultado do Tratamento , Estados UnidosRESUMO
Background Hospitals commonly provide a short-term supply of free P2Y12 inhibitors at discharge after myocardial infarction, but it is unclear if these programs improve medication persistence and outcomes. The ARTEMIS (Affordability and Real-World Antiplatelet Treatment Effectiveness After Myocardial Infarction Study) trial randomized hospitals to usual care versus waived P2Y12 inhibitor copayment costs for 1-year post-myocardial infarction. Whether the impact of this intervention differed between hospitals with and without pre-existing medication assistance programs is unknown. Methods and Results In this post hoc analysis of the ARTEMIS trial, we examined the associations of pre-study free medication programs and the randomized copayment voucher intervention with P2Y12 inhibitor persistence (measured by pharmacy fills and patient report) and major adverse cardiovascular events using logistic regression models including a propensity score. Among 262 hospitals, 129 (49%) offered pre-study free medication assistance. One-year P2Y12 inhibitor persistence and major adverse cardiovascular events risks were similar between patients treated at hospitals with and without free medication programs (adjusted odds ratio 0.93, 95% CI, 0.82-1.05 and hazard ratio 0.92, 95% CI, 0.80-1.07, respectively). The randomized copayment voucher intervention improved persistence, assessed by pharmacy fills, in both hospitals with (53.6% versus 44.0%, adjusted odds ratio 1.45, 95% CI, 1.20-1.75) and without (59.0% versus 48.3%, adjusted odds ratio 1.46, 95% CI, 1.25-1.70) free medication programs (Pinteraction=0.71). Differences in patient-reported persistence were not significant after adjustment. Conclusions While hospitals commonly report the ability to provide free short-term P2Y12 inhibitors, we did not find association of this with medication persistence or major adverse cardiovascular events among patients with insurance coverage for prescription medication enrolled in the ARTEMIS trial. An intervention that provided copayment assistance vouchers for 1 year was successful in improving medication persistence in hospitals with and without pre-existing short-term medication programs. Registration URL: https://www.cliniâcaltrâials.gov/. Unique identifier: NCT02406677.
Assuntos
Dedutíveis e Cosseguros/economia , Custos de Medicamentos , Gastos em Saúde , Adesão à Medicação , Infarto do Miocárdio/economia , Inibidores da Agregação Plaquetária/economia , Antagonistas do Receptor Purinérgico P2Y/economia , Idoso , Análise Custo-Benefício , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/tratamento farmacológico , Inibidores da Agregação Plaquetária/uso terapêutico , Antagonistas do Receptor Purinérgico P2Y/uso terapêutico , Melhoria de Qualidade/economia , Indicadores de Qualidade em Assistência à Saúde/economia , Fatores de Tempo , Resultado do Tratamento , Estados UnidosRESUMO
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.
Assuntos
Síndrome Coronariana Aguda/tratamento farmacológico , Síndrome Coronariana Aguda/economia , Citocromo P-450 CYP2C19/genética , Custos de Medicamentos , Testes Farmacogenômicos/economia , Variantes Farmacogenômicos , Inibidores da Agregação Plaquetária/economia , Inibidores da Agregação Plaquetária/uso terapêutico , Medicina de Precisão/economia , Síndrome Coronariana Aguda/sangue , Síndrome Coronariana Aguda/diagnóstico , Tomada de Decisão Clínica , Clopidogrel/economia , Clopidogrel/uso terapêutico , Citocromo P-450 CYP2C19/metabolismo , Humanos , Seleção de Pacientes , Inibidores da Agregação Plaquetária/efeitos adversos , Inibidores da Agregação Plaquetária/farmacocinética , Cloridrato de Prasugrel/economia , Cloridrato de Prasugrel/uso terapêutico , Valor Preditivo dos Testes , Ticagrelor/economia , Ticagrelor/uso terapêutico , Resultado do TratamentoRESUMO
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.
Assuntos
Síndrome Coronariana Aguda/economia , Síndrome Coronariana Aguda/terapia , Citocromo P-450 CYP2C19/genética , Custos de Medicamentos , Técnicas de Diagnóstico Molecular/economia , Intervenção Coronária Percutânea , Variantes Farmacogenômicos , Inibidores da Agregação Plaquetária/economia , Inibidores da Agregação Plaquetária/uso terapêutico , Síndrome Coronariana Aguda/genética , Aspirina/economia , Aspirina/uso terapêutico , Clopidogrel/economia , Clopidogrel/uso terapêutico , Análise Custo-Benefício , Técnicas de Apoio para a Decisão , Terapia Antiplaquetária Dupla/economia , Humanos , Intervenção Coronária Percutânea/efeitos adversos , Inibidores da Agregação Plaquetária/efeitos adversos , Valor Preditivo dos Testes , Anos de Vida Ajustados por Qualidade de Vida , Ticagrelor/economia , Ticagrelor/uso terapêutico , Fatores de Tempo , Resultado do TratamentoRESUMO
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.
Assuntos
Aspirina/economia , Clopidogrel/economia , Doença Arterial Periférica/complicações , Inibidores da Agregação Plaquetária/economia , Prevenção Secundária/economia , Aspirina/administração & dosagem , Clopidogrel/administração & dosagem , Análise Custo-Benefício , Gastos em Saúde , Humanos , Cadeias de Markov , Modelos Econométricos , Inibidores da Agregação Plaquetária/administração & dosagem , Anos de Vida Ajustados por Qualidade de Vida , Prevenção Secundária/métodos , Trombose/etiologia , Trombose/prevenção & controleRESUMO
OBJECTIVE: To evaluate the cost-effectiveness of multigene testing (CYP2C19, SLCO1B1, CYP2C9, VKORC1) compared with single-gene testing (CYP2C19) and standard of care (no genotyping) in acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI) from Medicare's perspective. METHODS: A hybrid decision tree/Markov model was developed to simulate patients post-PCI for ACS requiring antiplatelet therapy (CYP2C19 to guide antiplatelet selection), statin therapy (SLCO1B1 to guide statin selection), and anticoagulant therapy in those that develop atrial fibrillation (CYP2C9/VKORC1 to guide warfarin dose) over 12 months, 24 months, and lifetime. The primary outcome was cost (2016 US dollar) per quality-adjusted life years (QALYs) gained. Costs and QALYs were discounted at 3% per year. Probabilistic sensitivity analysis (PSA) varied input parameters (event probabilities, prescription costs, event costs, health-state utilities) to estimate changes in the cost per QALY gained. RESULTS: Base-case-discounted results indicated that the cost per QALY gained was $59 876, $33 512, and $3780 at 12 months, 24 months, and lifetime, respectively, for multigene testing compared with standard of care. Single-gene testing was dominated by multigene testing at all time horizons. PSA-discounted results indicated that, at the $50 000/QALY gained willingness-to-pay threshold, multigene testing had the highest probability of cost-effectiveness in the majority of simulations at 24 months (61%) and over the lifetime (81%). CONCLUSIONS: On the basis of projected simulations, multigene testing for Medicare patients post-PCI for ACS has a higher probability of being cost-effective over 24 months and the lifetime compared with single-gene testing and standard of care and could help optimize medication prescribing to improve patient outcomes.
Assuntos
Síndrome Coronariana Aguda/economia , Síndrome Coronariana Aguda/terapia , Anticoagulantes/economia , Anticoagulantes/uso terapêutico , Custos de Medicamentos , Inibidores de Hidroximetilglutaril-CoA Redutases/economia , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Intervenção Coronária Percutânea/economia , Testes Farmacogenômicos/economia , Variantes Farmacogenômicos , Inibidores da Agregação Plaquetária/economia , Inibidores da Agregação Plaquetária/uso terapêutico , Síndrome Coronariana Aguda/diagnóstico , Síndrome Coronariana Aguda/mortalidade , Idoso , Anticoagulantes/efeitos adversos , Análise Custo-Benefício , Citocromo P-450 CYP2C19/genética , Citocromo P-450 CYP2C9/genética , Árvores de Decisões , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Transportador 1 de Ânion Orgânico Específico do Fígado/genética , Masculino , Cadeias de Markov , Medicare/economia , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/mortalidade , Inibidores da Agregação Plaquetária/efeitos adversos , Medicina de Precisão/economia , Valor Preditivo dos Testes , Anos de Vida Ajustados por Qualidade de Vida , Reprodutibilidade dos Testes , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Estados Unidos , Vitamina K Epóxido Redutases/genéticaRESUMO
BACKGROUND: Administrative data were used to investigate changes in hospitalizations for atrial fibrillation (AF), AF-related stroke, and treatment patterns between 2012 and 2016. METHODS: From the 'Ricerca e Salute' database, a population- and patient-based repository involving >12 million inhabitants and linking demographics, prescriptions, and hospital discharge records, all patients discharged alive with a diagnosis of AF between 2012 and 2015 were followed for 1â¯year. RESULTS: A total of 194,030 AF patients were included. The number of AF cases increased ~10% over time, from 4.0 per 1,000 inhabitants in 2012 to 4.4 per 1,000 in 2015. At 1â¯year, hospitalizations for ischemic stroke decreased from 21.3 per 1,000 patients with AF in 2012-2013 to 14.7 per 1,000 in 2015-2016 (-31%, 95% CI -18 to -41). Over the same period, oral anticoagulant (OAC) use increased from 56.7% to 64.4% (+14%, 95% CI +8 to +26), vitamin K antagonist use decreased (from 55.9 to 36.7%; -34%, 95% CI -21 to -44), whereas direct OACs (DOACs) increased (from <1% in 2012 to 27.7% in 2015). Antiplatelet prescriptions fell from 42.6% in 2012 to 28.1% in 2015. Hospitalizations for major bleeds, mainly gastrointestinal, increased from 1.5 in 2012-2013 to 2.3 in 2015-2016, whereas hemorrhagic stroke admissions decreased from 6.5 to 4.1. CONCLUSIONS: There was a slight increase in the prevalence of AF between 2012 and 2015, whereas the overall use of antiplatelet agents decreased and that of OAC, particularly DOACs, increased. Over the same period, 1-year hospitalizations for ischemic stroke declined substantially, with a declining rate of hemorrhagic strokes.
Assuntos
Anticoagulantes/administração & dosagem , Fibrilação Atrial/epidemiologia , Hospitalização/tendências , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/prevenção & controle , Administração Oral , Idoso , Anticoagulantes/economia , Antitrombinas/administração & dosagem , Antitrombinas/economia , Fibrilação Atrial/complicações , Fibrilação Atrial/economia , Área Programática de Saúde/estatística & dados numéricos , Inibidores do Fator Xa/administração & dosagem , Inibidores do Fator Xa/economia , Feminino , Hemorragia Gastrointestinal/induzido quimicamente , Hemorragia Gastrointestinal/epidemiologia , Gastos em Saúde , Hemorragia/induzido quimicamente , Hemorragia/epidemiologia , Hospitalização/estatística & dados numéricos , Humanos , Itália/epidemiologia , Masculino , Inibidores da Agregação Plaquetária/administração & dosagem , Inibidores da Agregação Plaquetária/economia , Estudos Retrospectivos , Acidente Vascular Cerebral/economia , Acidente Vascular Cerebral/etiologia , Fatores de Tempo , Vitamina K/antagonistas & inibidoresRESUMO
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.
Assuntos
Síndrome Coronariana Aguda/tratamento farmacológico , Clopidogrel/administração & dosagem , Medicamentos Genéricos/administração & dosagem , Doença Arterial Periférica/tratamento farmacológico , Síndrome Coronariana Aguda/economia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Clopidogrel/economia , Medicamentos Genéricos/economia , Feminino , Custos de Cuidados de Saúde , Humanos , Masculino , Adesão à Medicação/estatística & dados numéricos , Pessoa de Meia-Idade , Doença Arterial Periférica/economia , Inibidores da Agregação Plaquetária/administração & dosagem , Inibidores da Agregação Plaquetária/economia , Estudos Retrospectivos , Espanha , Adulto JovemRESUMO
OBJECTIVES: We aimed to estimate the annual pharmaceutical costs for patients with stable coronary artery disease, using Australian administrative data, comparing patients who had undergone interventional treatment with those had not. We also aimed to compare the duration of dual antiplatelet therapy (DAPT) prescription in the real-world, with recommended guidelines. DESIGN: An observational study using administrative data. PARTICIPANTS: We used data from the QSkin study, a population-based prospective study assessing skin cancer risk. Participants were invited from the Queensland population, not based on perceived skin cancer risk, and had consented to future use of their data for approved research projects. MAIN OUTCOME MEASURES: We calculated 12-month costs of pharmaceutical therapy for coronary artery disease for patients in each of three clinically relevant groups: medical therapy only, following coronary stent implantation and following coronary artery bypass graft surgery. We measured the duration of DAPT following stent implantation and total duration of DAPT, where it was prescribed, in the medical therapy only group. RESULTS: Estimated mean annual pharmaceutical costs were highest in the stent group at AUD$1920, compared with AUD$1481 in the medical therapy group, and AUD$881 in the coronary artery bypass group. There were similar rates of prescriptions of symptom relief drugs following stent insertion, compared with the medical therapy only group. The median duration of DAPT in the stent group was 16, and 31 months in the medical therapy group. CONCLUSIONS: Our results suggest that despite the common expectation that the burden of medical therapy is reduced following coronary stent insertion for stable coronary artery disease, this does not occur in practice. Many patients also appear to continue DAPT longer than guidelines recommend, which may put them at unnecessarily elevated risk of bleeding events.
Assuntos
Doença da Artéria Coronariana/dietoterapia , Doença da Artéria Coronariana/economia , Stents Farmacológicos/economia , Custos de Cuidados de Saúde/estatística & dados numéricos , Intervenção Coronária Percutânea/economia , Inibidores da Agregação Plaquetária/economia , Idoso , Doença da Artéria Coronariana/epidemiologia , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Queensland , Medição de RiscoRESUMO
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.
Assuntos
Testes Farmacogenômicos/economia , Medicina de Precisão/economia , Avaliação da Tecnologia Biomédica/métodos , Síndrome Coronariana Aguda/tratamento farmacológico , Clopidogrel/economia , Clopidogrel/uso terapêutico , Análise Custo-Benefício , Citocromo P-450 CYP2C19/genética , Tomada de Decisões , Interações Medicamentosas , Humanos , Modelos Econômicos , Testes Farmacogenômicos/métodos , Inibidores da Agregação Plaquetária/economia , Inibidores da Agregação Plaquetária/uso terapêutico , Cloridrato de Prasugrel/economia , Cloridrato de Prasugrel/uso terapêutico , Medicina de Precisão/métodos , Inibidores da Bomba de Prótons/farmacologia , Anos de Vida Ajustados por Qualidade de Vida , Medição de Risco , Ticagrelor/economia , Ticagrelor/uso terapêutico , IncertezaRESUMO
OBJECTIVE: To evaluate the cost effectiveness of various preeclampsia screening and aspirin prophylaxis strategies, including a strategy based on biomarker and ultrasound measures. METHODS: We designed a decision analysis to compare preeclampsia-related costs and effects of four strategies for aspirin use in pregnancy initiated before 16 weeks of gestation to prevent preeclampsia. The four strategies were: 1) no aspirin use, 2) biomarker and ultrasound measure-predicated use, 3) use based on the U.S. Preventive Services Task Force guidelines, and 4) universal aspirin use. Our outcomes were preeclampsia-related costs and number of cases per 100,000 pregnant women. Using a threshold of $90,843 per case of preeclampsia, one-way, two-way, and Monte-Carlo sensitivity analyses incorporating varying probabilities of risk reduction due to aspirin use, aspirin-related side effects, and costs were performed to identify ranges at which costs and risks of aspirin-related complications shifted the preferred strategy. RESULTS: Compared with universal aspirin administration, the use of U.S. Preventive Services Task Force guidelines is associated with $8,011,725 higher health care costs and 346 additional cases of preeclampsia per 100,000 pregnant women; biomarker and ultrasound screening is associated with an additional $19,216,551 and 308 additional cases. Similarly, no aspirin use is associated with an increased cost of $18,750,381 and 762 additional cases. Thus, universal aspirin use dominated all three other strategies. In a Monte Carlo simulation of 10,000 pregnant women, universal aspirin was the preferred strategy in 91% of simulations. The U.S. Preventive Task Force screen was preferred in 8.5% of simulations, and biomarker and ultrasound screening and no aspirin were preferred in 0% and 0.5% of simulations, respectively. CONCLUSION: Over a broad range of assumptions, universal aspirin administration is associated with fewer cases of preeclampsia and fewer costs relative to no aspirin administration and aspirin administration based on serum and ultrasound measures or clinical risk factors.
Assuntos
Aspirina/economia , Inibidores da Agregação Plaquetária/economia , Pré-Eclâmpsia/economia , Pré-Eclâmpsia/prevenção & controle , Diagnóstico Pré-Natal/economia , Adulto , Aspirina/uso terapêutico , Biomarcadores/análise , Análise Custo-Benefício , Técnicas de Apoio para a Decisão , Feminino , Humanos , Inibidores da Agregação Plaquetária/uso terapêutico , Gravidez , Fatores de RiscoRESUMO
PURPOSE: Perform a cost-effectiveness analysis comparing strategies for selecting P2Y12 inhibitors in acute coronary syndrome (ACS). METHODS: Six strategies for selection of P2Y12 inhibitors in ACS were compared from the US healthcare system perspective: (1) clopidogrel for all (universal clopidogrel); (2) ticagrelor guided by platelet reactivity assay (PRA; clopidogrel + phenotype); (3) ticagrelor use only in CYP2C19 poor metabolizers (genotype + conservative ticagrelor); (4) ticagrelor use in both CYP2C19 intermediate and poor metabolizers (genotype + liberal ticagrelor); (5) ticagrelor use only in patients with CYP2C19 polymorphisms and clopidogrel nonresponse by PRA (genotype + phenotype); and (6) ticagrelor for all (universal ticagrelor). A decision model was developed to model major adverse cardiovascular events and bleeding during 1 year of treatment with a P2Y12 inhibitor. Model inputs were identified from the literature. Lifetime costs were adjusted to 2017 US dollars; quality-adjusted life-years (QALYs) were projected using a Markov model. The primary endpoint was the incremental cost-effectiveness compared to the next best option along the cost-effectiveness continuum. Sensitivity analyses were performed on all model inputs to assess their influence on the incremental cost-effectiveness. RESULTS: In the base case analysis, incremental cost-effectiveness ratios (ICER) for the clopidogrel + phenotype, genotype + liberal ticagrelor, and universal ticagrelor strategies were $12,119/QALY, $29,412/QALY, and $142,456/QALY, respectively. Genotype + conservative ticagrelor and genotype + phenotype were not cost-effective due to second-order dominance. Genotype + liberal ticagrelor compared to clopidogrel + phenotype demonstrated the highest acceptance (97%) at a willingness to pay (WTP) threshold of $100,000/QALY. CONCLUSION: Cost-effective strategies to personalize P2Y12 inhibition in ACS include clopidogrel +phenotype and genotype + liberal ticagrelor. Universal ticagrelor may be considered cost-effective at a higher WTP threshold ($150,000/QALY). Genotype + liberal ticagrelor exhibited the highest acceptability compared to clopidogrel + phenotype over the widest range of WTP thresholds and may be preferred.
Assuntos
Síndrome Coronariana Aguda/tratamento farmacológico , Síndrome Coronariana Aguda/economia , Custos de Medicamentos , Testes Farmacogenômicos/economia , Inibidores da Agregação Plaquetária/economia , Inibidores da Agregação Plaquetária/uso terapêutico , Medicina de Precisão/economia , Antagonistas do Receptor Purinérgico P2Y/economia , Antagonistas do Receptor Purinérgico P2Y/uso terapêutico , Síndrome Coronariana Aguda/diagnóstico , Tomada de Decisão Clínica , Análise Custo-Benefício , Citocromo P-450 CYP2C19/genética , Citocromo P-450 CYP2C19/metabolismo , Técnicas de Apoio para a Decisão , Árvores de Decisões , Genótipo , Humanos , Cadeias de Markov , Modelos Econômicos , Seleção de Pacientes , Variantes Farmacogenômicos , Fenótipo , Inibidores da Agregação Plaquetária/efeitos adversos , Antagonistas do Receptor Purinérgico P2Y/efeitos adversos , Anos de Vida Ajustados por Qualidade de Vida , Fatores de Tempo , Resultado do TratamentoRESUMO
A study designed to test whether eliminating copays would improve adherence to antiplatelet therapy showed that, yes, indeed, it does. But the results also showed no reduction in major cardiovascular events among those who stuck with the medication.
Assuntos
Inibidores da Agregação Plaquetária/economia , Seguro , Adesão à MedicaçãoRESUMO
BACKGROUND: There is underutilization of appropriate medications for secondary prevention of cardiovascular disease (CVD). METHODS: Usual care (UC) was compared to polypill-based care with 3 versions using a validated micro-simulation model in the NHANES population with prior CVD. UC included individual prescription of up to 4 drug classes (antiplatelet agents, beta-blockers, renin-angiotensin-aldosterone inhibitors and statins). The polypills modeled were aspirin 81 mg, atenolol 50 mg, ramipril 5 mg, and either simvastatin 40 mg (Polypill I), atorvastatin 80 mg (Polypill II), or rosuvastatin 40 mg (Polypill III). Baseline medication use and adherence came from United Healthcare claims data. RESULTS: When compared to UC, there were annual reductions of 130,000 to 178,000 myocardial infarctions and 54,000 to 74,000 strokes using Polypill I and II, respectively. From a health sector perspective, in incremental analysis the ICERs for Polypill I and II were $20,073/QALY and $21,818/QALY respectively; Polypill III was dominated but had a similar cost-effectiveness ratio to Polypill II when compared directly to usual care. From a societal perspective, Polypill II was cost-saving and dominated all strategies. Over a 5-year period, those taking Polypill I and II compared to UC saved approximately $12 and $6 per-patient-per-year alive, respectively. Polypill II was the preferred strategy in 98% of runs at a willingness to pay of $50,000 in the probability sensitivity analysis. CONCLUSIONS: Use of a polypill has a favorable cost profile for secondary CVD prevention in the United States. Reductions in CVD-related healthcare costs outweighed medication cost increases on a per-patient-per-year basis, suggesting that a polypill would be economically advantageous to both patients and payers.
Assuntos
Orçamentos , Doenças Cardiovasculares/prevenção & controle , Combinação de Medicamentos , Prevenção Secundária/economia , Acidente Vascular Cerebral/prevenção & controle , Antagonistas Adrenérgicos beta/economia , Aspirina/economia , Atenolol/economia , Doenças Cardiovasculares/economia , Doenças Cardiovasculares/mortalidade , Redução de Custos , Análise Custo-Benefício , Custos de Medicamentos , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/economia , Expectativa de Vida , Masculino , Adesão à Medicação , Pessoa de Meia-Idade , Inquéritos Nutricionais , Inibidores da Agregação Plaquetária/economia , Ramipril/economia , Sistema Renina-Angiotensina , Prevenção Secundária/métodos , Prevenção Secundária/estatística & dados numéricos , Acidente Vascular Cerebral/economia , Acidente Vascular Cerebral/mortalidade , Estados UnidosRESUMO
PURPOSE: This study was conducted to examine the use of optimal medical therapy (OMT), consisting of an antiplatelet, a ß-blocker, an angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (ACEI/ARB), and a statin combined, after hospital discharge and its relationship with direct medical costs in patients with acute coronary syndromes (ACS) in Tianjin, China. METHODS: Data were obtained from the Tianjin Urban Employee Basic Medical Insurance database (2011-2015). Data from adult patients with ≥1 hospitalization for ACS between January 2012 and December 2014 were included. Medications including antiplatelets, ß-blockers, ACEIs/ARBs, and statins at discharge were recorded, with OMT defined as the use of all 4 indicated medications. Propensity-score matching was conducted to form matched OMT and non-OMT cohorts based on baseline differences. All-cause and ACS-related health care resource utilization and direct medical costs during a 12-month follow-up period were assessed and compared between cohorts. Generalized linear modeling was conducted to assess the association between OMT at discharge and direct medical costs. FINDINGS: A total of 22,041 patients were identified (mean age, 64.7 [10.7] years; 45.6% female), of whom 15.1% (3336) received OMT at discharge. The OMT cohort had fewer patients hospitalized for any cause during follow-up compared with the matched non-OMT cohort (38.1% vs 43.2%; P < 0.001), which was further associated with fewer hospitalizations (1.55 vs 1.64; P = 0.019) and shorter annualized length of stay (15.9 vs 17.2 d; P = 0.041). Despite higher costs of outpatient services (9958 vs 10,060 Chinese yuan [CNY] [P = 0.006]; adjusted difference, +456 CNY [P = 0.004]) (year-2014 1 USD = 6.20 CNY), the OMT cohort had significantly lower all-cause total costs (20,771 vs 22,877 CNY [P = 0.174]; adjusted difference, -2089 CNY [P = 0.006]), driven by lower costs of inpatient services (10,813 vs 12,817 CNY [P < 0.001]; adjusted difference, -2184 CNY [P = 0.001]). The difference in ACS-related total costs between the 2 cohorts was not statistically significant (8535 vs 9304 CNY [P = 0.128]; adjusted difference, -558 CNY [P = 0.214]). IMPLICATIONS: Receiving OMT at discharge was associated with fewer hospitalizations and lower all-cause direct medical costs in these patients with ACS in China. Strategies are needed to improve OMT prescribing rates at discharge, which would lead to better clinical prognosis and total cost-savings among patients with ACS in China.
Assuntos
Síndrome Coronariana Aguda/tratamento farmacológico , Síndrome Coronariana Aguda/economia , Antagonistas Adrenérgicos beta/economia , Antagonistas Adrenérgicos beta/uso terapêutico , Idoso , Inibidores da Enzima Conversora de Angiotensina/economia , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , China , Bases de Dados Factuais , Feminino , Custos de Cuidados de Saúde , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/economia , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Masculino , Pessoa de Meia-Idade , Alta do Paciente , Inibidores da Agregação Plaquetária/economia , Inibidores da Agregação Plaquetária/uso terapêutico , Estudos RetrospectivosRESUMO
BACKGROUND: The cost-effectiveness of newer drug-eluting stents (DES) such as biodegradable-polymer or polymer-free stents with shorter dual antiplatelet therapy (DAPT) duration is unknown. We evaluated the cost-effectiveness of treatment with newer DES that may allow for shorter DAPT duration. PATIENTS AND METHODS: We performed a cost-effectiveness analysis of treatment with newer DES platforms followed by 1 or 3 months of DAPT compared with standard second-generation DES followed by 6 or 12 months of DAPT in patients with stable coronary disease. A Markov model simulated distinct health states over a lifetime. Probabilistic sensitivity analysis and one-way sensitivity analyses were performed. A high-risk bleeding scenario was also evaluated. RESULTS: Among patients with typical bleeding risk, second-generation DES and 6 months of DAPT was less expensive and resulted in marginally higher quality-adjusted life years compared with other strategies. A newer DES platform and 3 months of DAPT was preferred when the risk of fatal bleeding was two times greater than baseline, or when bleeding increased long-term mortality by a factor of 1.5. In a probabilistic sensitivity analysis, second-generation DES and 6 months of DAPT was preferred in 58% of iterations, whereas in a high-risk bleeding patient scenario, a newer DES and 3 months of DAPT was preferred in 52% of iterations. CONCLUSION: A DES that allows 3 months of DAPT without increasing stent-related events is likely to be cost-effective among patients at elevated risk of bleeding, but not in patients with average bleeding risk.