RESUMO
BACKGROUND: Patients with cancer have an elevated risk of venous thromboembolism. Importantly, patients with cancer, who have metastatic disease, renal insufficiency, or are receiving anticancer therapy, have an even higher risk of a recurrent event. Similarly, the risk of recurrent venous thromboembolism is higher than the risk of an initial event. To reduce the risk, extended duration of prophylaxis for up to six months with low-molecular-weight heparins such as dalteparin, enoxaparin, nadroparin, and tinzaparin is recommended by international guidelines. In this paper, the clinical and economic literature is reviewed to provide evidenced based recommendations based on clinical benefit and economic value. METHODS: A systematic review of major databases was conducted from January 1996 to October 2016 for randomized controlled trials evaluating the four distinct low-molecular-weight heparins against a vitamin K antagonists control group for the prevention of recurrent venous thromboembolism in patients with active cancer. This was then followed by the application of the National Institute of Health and Clinical Excellence guidance to assess the quality of all trials that met the inclusion criteria. Finally, the cost-effectiveness literature supporting the value proposition of each product was reviewed. RESULTS: Six randomized trials met the inclusion criteria. There were one, two, and three trials that compared dalteparin, tinzaparin, and enoxaparin to a vitamin K antagonists control group. However, there were no trials for nadroparin in the setting of secondary venous thromboembolism prevention. In addition, only the dalteparin and one of the tinzaparin trials were of high quality and adequately powered. Of the two studies, only the dalteparin trial reported a statistically significant benefit in terms of venous thromboembolism absolute risk reduction when compared to a vitamin K antagonists control group (HR = 0.48; p = 0.002). In addition, there was robust pharmacoeconomic data from Canada, the Netherlands, France, and Austria supporting the cost-effectiveness of dalteparin for this indication. There were no such studies for any of the other agents. CONCLUSIONS: The totality of high-quality clinical and cost-effectiveness data supports the use of dalteparin over other low-molecular-weight heparins for preventing recurrent venous thromboembolism in patients with cancer.
Assuntos
Heparina de Baixo Peso Molecular/farmacologia , Neoplasias/complicações , Prevenção Secundária/métodos , Tromboembolia Venosa , Anticoagulantes/farmacologia , Análise Custo-Benefício , Humanos , Resultado do Tratamento , Tromboembolia Venosa/tratamento farmacológico , Tromboembolia Venosa/etiologiaRESUMO
BACKGROUND: Patients with cancer are at increased risk of venous thromboembolism (VTE) and the risk is further elevated after a primary VTE. To reduce the risk of recurrent events, extended prophylaxis with vitamin K antagonists (VKA) is available for use. However, in a large randomized trial (Comparison of Low-Molecular-Weight Heparin versus Oral Anticoagulant Therapy for the Prevention of Recurrent Venous Thromboembolism in Patients with Cancer [CLOT]; Lee et al), extended duration dalteparin reduced the relative risk of recurrent VTE by 52% compared to VKA (p=0.002). A recent subgroup analysis of patients with moderate-to-severe renal impairment also revealed lower absolute VTE rates with dalteparin (3% vs. 17%; p=0.011). To measure the economic value of dalteparin as an alternative to VKA, a patient-level cost utility analysis was conducted from a Canadian perspective. METHODS: Resource use data captured during the CLOT trial were extracted and linked to 2015 Canadian unit cost estimates. Health state utilities were then measured using the Time-Trade-Off technique in 24 randomly selected members of the general Canadian public to estimate the gains in quality-adjusted life years (QALYs). RESULTS: For the entire CLOT trial population (n=676), the dalteparin group had significantly higher mean costs compared to the VKA group ($Can5,771 vs. $Can2,569; p<0.001). However, the utility assessment revealed that 21 of 24 respondents (88%) selected dalteparin over VKA, with an associated gain of 0.14 (95% confidence interval [CI]: 0.10-0.18) QALYs. When the incremental cost of dalteparin was combined with the QALY gain, dalteparin had a cost of $Can23,100 (95% CI: $Can19,200-$Can25,800) per QALY gained. The analysis in patients with renal impairment suggested even better economic value with the cost per QALY gained being <$14,000. CONCLUSION: Extended duration dalteparin is a cost-effective alternative to VKA for the prevention of recurrent VTE in patients with cancer, especially in those with renal impairment.
RESUMO
BACKGROUND: International guidelines recommend extended duration secondary prophylaxis in cancer patients who develop primary venous thromboembolism (VTE). Agent selection is guided in part by one large randomized trial (i.e., CLOT; Lee et al., N Engl J Med 349:146-53, 2003) which demonstrated that dalteparin reduced the relative risk of recurrence by 52% compared with oral vitamin K antagonists (VKA; HR = 0.48, 95% CI, 0.30 to 0.77). In a subgroup analysis from that same trial, patients with renal impairment also derived benefit with dalteparin (VTE rates = 3% vs. 17%; p = 0.011). To measure the economic value of secondary VTE prophylaxis with dalteparin, a patient-level pharmacoeconomic analysis was conducted from the Austrian and French healthcare system perspectives. METHODS: Chapter 1 Healthcare resource use collected during the CLOT trial was extracted and converted into direct cost estimates. Incremental cost differences between the dalteparin and VKA groups were then combined with health state utilities to measure the cost per quality-adjusted life year (QALY) gained. RESULTS: The dalteparin group had significantly higher costs than the VKA group in both countries (Austria: dalteparin = 2687 vs. VKA = 2012; France: dalteparin = 2053 vs. VKA = 1352: p < 0.001). However, when the incremental costs were combined with the utility gain, dalteparin had a cost of 6600 and 4900 per QALY gained in Austria and France, respectively. The analyses in patients with renal impairment suggested an even better economic profile, with the cost per QALY gained being less than 4000 in both countries. CONCLUSIONS: Secondary prophylaxis with dalteparin is a cost-effective alternative to VKA for the prevention of recurrent VTE in patients with cancer.
Assuntos
Anticoagulantes/uso terapêutico , Dalteparina/uso terapêutico , Neoplasias/complicações , Qualidade de Vida/psicologia , Tromboembolia Venosa/economia , Tromboembolia Venosa/prevenção & controle , Vitamina K/antagonistas & inibidores , Áustria , Análise Custo-Benefício , Dalteparina/administração & dosagem , Dalteparina/farmacologia , Feminino , França , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/tratamento farmacológico , RecidivaRESUMO
BACKGROUND: In a randomized trial (ie, Comparison of Low-Molecular-Weight Heparin versus Oral Anticoagulant Therapy for the Prevention of Recurrent Venous Thromboembolism in Patients with Cancer [CLOT]) that evaluated secondary prophylaxis of recurrent venous thromboembolism (VTE) in patients with cancer, dalteparin reduced the relative risk by 52% compared to oral vitamin K antagonists (VKAs; hazard ratio = 0.48, P = .002). A recent subgroup analysis in patients with moderate to severe renal impairment also revealed lower absolute VTE rates with dalteparin (3% vs 17%; P = .011). To measure the economic value of dalteparin in these populations, a pharmacoeconomic analysis was conducted from the Dutch health-care system perspective. METHODS: Resource utilization data contained within the CLOT trial database were extracted and converted into direct cost estimates. Univariate analysis was then conducted to compare the total cost of therapy between patients randomized to dalteparin or VKA therapy. Health state utilities were then measured in 24 members of the general public using the time trade-off technique. RESULTS: When all of the cost components were combined for the entire population (n = 676), the dalteparin group had significantly higher overall costs than the VKA control group (dalteparin = 2375 vs VKA = 1724; P < .001). However, dalteparin was associated with a gain of 0.14 (95% confidence interval [CI]: 0.10-0.18) quality-adjusted life years (QALYs) over VKA. When the incremental cost was combined with the utility gain, dalteparin had a cost of 4,697 (95% CI: 3824-4951) per QALY gained. CONCLUSION: Secondary prophylaxis with dalteparin is a cost-effective alternative to VKA for the prevention of recurrent VTE in patients with cancer.