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Cost-Effectiveness of Carbetocin Versus Oxytocin for Prevention Of THIEME 242 Original Article Cost-effectiveness of Carbetocin versus Oxytocin for Prevention of Postpartum Hemorrhage Resulting from Uterine Atony in Women at high-risk for bleeding in Colombia Rendimento da carbetocina versus oxitocina para a prevenção da hemorragia pós-parto resultante da atonia uterina em mulheres com alto risco de sangramento na Colômbia Yaneth Gil-Rojas1 Pieralessandro Lasalvia1 Fabián Hernández1 Camilo Castañeda-Cardona1 Diego Rosselli2 1 NeuroEconomix, Bogota, Colombia Address for correspondence Diego Rosselli, Department of Clinical 2 Department of Clinical Epidemiology and Biostatistics, Facultad de Epidemiology and Biostatistics, Facultad de Medicina de La Pontificia Medicina de la Pontificia Universidad Javeriana, Bogota, Colombia Universidad Javeriana, Carrera 7 No. 40–62, Bogota, Colombia (e-mail: [email protected]). Rev Bras Ginecol Obstet 2018;40:242–250. Abstract Objective To assess the cost-effectiveness of carbetocin versus oxytocin for preven- tion of postpartum hemorrhage (PPH) due to uterine atony after vaginal delivery/ cesarean section in women with risk factors for bleeding. Methods A decision tree was developed for vaginal delivery and another one for cesarean, in which a sequential analysis of the results was obtained with the use of carbetocin and oxytocin for prevention of PPH and related consequences. A third-party payer perspective was used; only direct medical costs were considered. Incremental costs and effectiveness in terms of quality-adjusted life years (QALYs) were evaluated for a one-year time horizon. The costs were expressed in 2016 Colombian pesos (1 USD ¼ 3,051 Col$). Results In the vaginal delivery model, the average cost of care for a patient receiving prophylaxis with uterotonic agents was Col$ 347,750 with carbetocin and Col$ 262,491 Keywords with oxytocin, while the QALYs were 0.9980 and 0.9979, respectively. The incremental cost- ► cost-effectiveness effectiveness ratio is above the cost-effectiveness threshold adopted by Colombia. In the ► carbetocin model developed for cesarean section, the average cost of a patient receiving prophylaxis ► oxytocin with uterotonics was Col$ 461,750 with carbetocin, and Col$ 481,866 with oxytocin, and ► prevention the QALYs were 0.9959 and 0.9926, respectively. Carbetocin has lower cost and is more postpartum effective, with a saving of Col$ 94,887 per avoided hemorrhagic event. hemorrhage Conclusion In case of elective cesarean delivery, carbetocin is a dominant alternative ► pregnancy in the prevention of PPH compared with oxytocin; however, it presents higher costs ► high-risk than oxytocin, with similar effectiveness, in cases of vaginal delivery. received DOI https://doi.org/ Copyright © 2018 by Thieme Revinter November 28, 2017 10.1055/s-0038-1655747. Publicações Ltda, Rio de Janeiro, Brazil accepted ISSN 0100-7203. April 4, 2018 Cost-effectiveness of Carbetocin versus Oxytocin for Prevention of Postpartum Gil-Rojas et al. 243 Resumo Objetivo Avaliar a relação custo-eficácia da carbetocina versus oxitocina para pre- venção de hemorragia pós-parto (HPP) vaginal e cesariana devido à atonia uterina em mulheres com fatores de risco para desenvolver sangramento. Métodos Foram desenvolvidos protocolos de manejo para parto vaginal e outra para parto por cesárea e analisados resultados obtidos com carbetocina e oxitocina na prevenção de HPP, assim como, consequências relacionadas à ocorrência do evento hemorrágico. A perspectiva utilizada foi a do terceiro pagador, portanto, apenas os custos médicos diretos foram levados em consideração. Os custos incrementais e a eficácia em termos de anos de vida ajustados pela qualidade (QALY) foram avaliados para um horizonte de tempo de um ano. Os custos foram expressos em pesos colombianos de 2016 (1 USD ¼ 3.051 Col$). Resultados No modelo de parto vaginal, o custo médio de cuidados para um paciente que recebeu profilaxia com agentes uterotônicos foi de Col$ 347.750 com carbetocina e Col$ 262.491 com oxitocina, enquanto os QALYs foram 0,9980 e 0,9979, respectiva- mente. O índice incremental de custo-efetividade está acima do limite de custo- Palavras chave efetividade adotado pela Colômbia. No modelo desenvolvido para parto por cesárea, o ► análise custo- custo médio do paciente que recebeu profilaxia com terapia uterotônica foi de Col$ eficiência 461.750 com carbetocina e Col$ 481.866 com oxitocina e os QALYs foram 0,9959 e ► carbetocina 0,9926, respectivamente. A carbetocina foi a alternativa com menor custo e maior ► oxitocina efetividade com uma economia de $94.887 por evento hemorrágico evitado. ► prevenção Conclusão A carbetocina no parto eletivo por cesárea é uma alternativa dominante ► hemorragia pós-parto na prevenção da PPH em relação à oxitocina; porém representa custos mais altos com ► gravidez de alto risco uma eficácia similar à da oxitocina no caso de parto vaginal. Introduction impact of active behavior applied in the local context in reducing maternal morbidity and mortality attributed to Postpartum hemorrhage (PPH) is definedasabloodloss PPH. greater than 500 mL within 24 hours postpartum and is Uterotonic agents for prevention of PPH include oxytocin, considered severe if the loss reaches 1,000 mL in the same methylergonovine, misoprostol and, more recently, carbeto- time interval.1 Postpartum hemorrhage affects 2% of cin. Oxytocin is the most frequently used agent but, due to its women in labor and it is responsible a quarter of maternal short half-life, it must be administered by intravenous infu- deaths. Uterine atony is the most common cause of this sion for sustained uterotonic activity. Carbetocin has an condition, but there may be others, such as genital trauma, efficacy and safety profile very similar to oxytocin and, uterine rupture, placental retention or maternal clotting due to its pharmacokinetic characteristics, has a longer – disorders. The methods of active behavior during delivery, uterotonic activity.4 6 According to the national guidelines, which include administration of prophylactic uterotonics oxytocin is the uterotonic agent of choice in prevention; after the birth of the newborn, early clamping and cutting however, international guidelines like those from the Royal of the umbilical cord, controlled traction of the cord, and College of Obstetricians and Gynaecologists (RCOG) and the uterine massage, have been associated with a considerable Society of Obstetricians and Gynaecologists of Canada reduction in the frequency of PPH.1 (SOGC) already include carbetocin as an alternative, mainly – Colombia has made progress in reducing maternal mor- in elective caesarean section.4 6 tality by 25%; however, there are still 400 deaths per year The objective of this evaluation was to estimate the associated with pregnancy and delivery.2 During 2012, when incremental cost-effectiveness ratio of carbetocin compared surveillance for the event of extreme maternal morbidity with oxytocin for prevention of PPH by uterine atony in was initiated, hemorrhagic complications ranked second, women with at least one risk factor for hemorrhage, from the with 23.1%. In 2013, 2014, 2015 and 2016, the proportions perspective of the Colombian health system. Women with of cases of extreme maternal morbidity attributed to hem- low risk for hemorrhage were not considered, since the orrhagic complications were 20%, 20.2%, 18% and 14.5%, indication for them is less clear. The study was based on respectively.3 Likewise, there has been a decline in the the guidelines established in the manual for the elaboration proportion of maternal deaths attributed to bleeding com- of economic assessments in health proposed by the national plications, reaching 13% in 2016.3 These values show the Institute of Technology Assessment in Health (IETS).7 Rev Bras Ginecol Obstet Vol. 40 No. 5/2018 244 Cost-effectiveness of Carbetocin versus Oxytocin for Prevention of Postpartum Gil-Rojas et al. Methods Decision Model A cost-effectiveness analysis was developed from the per- The models were constructed from the review of previous – spective of the third-party payer to compare the use of studies,10 14 and were discussed and validated by a group of carbetocin in the prevention of PPH with that of oxytocin thematic experts. Two decision trees were developed with in women with the presence of at least one risk factor for TreeAge Pro Suite 2009 (TreeAge Software Inc., Williams- hemorrhage due to uterine atony. Among the risk factors town, MA, USA), one for cesarean section (►Fig. 1) and one described for PPH due to uterine atony are: multiple gesta- for vaginal delivery (►Fig. 2). The model begins with women tion, polyhydramnios, macrosomia, large multiparous, se- with the presence of at least one risk factor for PPH due to vere hydrocephalus, prolonged labor and chorioamnionitis.8 uterine atony who can receive prophylaxis with any of the A model for vaginal delivery and another one for cesarean technologies being evaluated: carbetocin or oxytocin. The delivery are presented separately because the characteristics first branch defines the occurrence or not of PPH (blood of these populations may change, as well as risk factors and loss > 500 mL), which corresponds to an analysis of the response to interventions. The main outcome was preven- response to preventive interventions. Carbetocin is available tion of PPH, defined as a blood loss exceeding 500 mL.9 Also, as an injectable solution of 100 mcg/mL and is a drug for as part of the sequential analysis, the consequences of the hospital use that should be administered in a single dose of hemorrhagic event with each of the alternatives were con- 100 mcg in both vaginal and cesarean deliveries. Oxytocin is sidered, particularly the treatment of PPH, use of additional available in an injectable solution of 5 IU/mL or 10 IU/mL, and uterotonics and the requirement of surgical intervention. the recommended dose in cases of vaginal delivery is 5 to 10 Considering that there are several outcomes that measure IU, intramuscularly, but in case of cesarean section, an IV the effectiveness of treatment (prevention of PPH, use of bolus of 5 IU is recommended followed by an infusion of additional uterotonics, adverse events), quality-adjusted 30 IU.
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