DOI: 10.
18585/inabj.
Cost Effectiveness Analysis of Hematemesis-Melena Treatment in Cirrhosis .
e Queljoe D) Indones Biomed J.
: 43-50
RESEARCH ARTICLE
Cost-Effectiveness Analysis of Pharmacotherapy for Hematemesis-Melena Treatment in Hospitalized Patients with Hepatic Cirrhosis Doddy de Queljoe1.
Amelia Lorensia1,E.
Liana Widharta1.
Sugiarto Widjaja2 Pharmacy Faculty.
Surabaya University.
Jl.
Ngagel Jaya Selatan 169.
Surabaya.
Indonesia Adi Husada Undaan Wetan Hospital.
Jl.
Undaan Wetan No.
Surabaya.
Jawa Timur.
Indonesia Corresponding author.
E-mail: amelia.
lorensia@gmail.
Abstract ACKGROUND: Acute variceal haemorrhage is a complication of cirrhosis that can be life It is a pharmacistAos duty to ensure therapeutic and pharmaceutical care which is not only safe and effective for the patient but also is cost-effective in order to attain improvement of the patientAos quality of Therefore, pharmacoeconomic evaluation especially cost-effectiveness analysis (CEA), which compares costs and consequences of drug therapy, is needed.
This study was aimed to evaluate the therapeutic cost-effectiveness of hematemesis-melena treatment in hepatic cirrhotic patients.
METHODS: A total of 42 patients receiving vitamin K and vitamin K-transamin were studied retrospectively from patientsAo medical records in 2 years and analyzed with cost-effectiveness grid and average cost-effectiveness ratio (ACER) based on Child-Turcotte-Pugh (CTP) Score.
Abstrak ATAR BELAKANG: Pendarahan varises akut merupakan komplikasi sirosis yang dapat mengacam jiwa.
Hal ini merupakan tugas farmasis untuk memastikan terapi dan pelayanan kefarmasian yang tidak hanya aman bagi pasien tetapi juga mempunyai biaya yang efektif yang bertujuan untuk memperbaiki kualitas hidup pasien.
Oleh karena itu, diperlukan evaluasi farmakoekonomi terutama cost-effectiveness analysis (CEA) yang membandingkan biaya dan konsekuensi dari terapi hematemesis-melena pada pasien sirosis hepatik.
METODE: Total dari 42 pasien yang menerima vitamin K dan vitamin K-transamin diteliti secara retrospektif dari rekam medik selama 2 tahun, dan dianalisis dengan costeffectiveness grid dan average cost-effectiveness ratio (ACER) berdasarkan Child-Turcotte-Pugh (CTP) Score.
RESULTS: Cost-effectiveness grid was dominant for vitamin K in patients with CTP Score A.
ACER analysis showed a lower score for vitamin K in all patients included CTP Score classification.
There was no significant difference in duration of cessation of bleeding treatment in patients with vitamin K compared with vitamin K-transamin in patients with CTP Score A and B, while significant difference was found in patients with CTP Score C.
HASIL: Cost-effectiveness grid menunjukkan bahwa dominant untuk vitamin K pada pasien dengan CTP Score Analisis ACER menunjukkan nilai yang lebih rendah pada vitamin K pada semua pasien meliputi klasifikasi CTP Score.
Tidak ada perbedaan bermakna untuk durasi dari penghentian terapi pendarahan pada pasien dengan vitamin K dibandingkan dengan vitamin K-transamin pada pasien dengan CTP Score A dan B, sedangkan perbedaan signifikan ditemukan pada pasien dengan CTP Score C.
CONCLUSION: Vitamin K appeared to be more costeffective as compared with vitamin K-transamin in all The use of vitamin K had greater benefit than the combination with transamin in all patients and CTP Score classification, and thus should be considered as a primary Therefore, transamin addition as an alternative therapy for hepatic cirrhosis patients with hematemesis- KESIMPULAN: Vitamin K terbukti lebih efektif biaya dibandingkan dengan vitamin K-transamin pada semua Penggunaan vitamin K memiliki keuntungan yang lebih besar dibandingkan dengan kombinasi dari transamin pada semua pasien dan klasifikasi CTP Score, sehingga seharusnya dipertimbangkan sebagai terapi primer.
Oleh karena itu penambahan transamin sebagai terapi alternatif The Indonesian Biomedical Journal.
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melena should be considered.
pada pasien sirosis hepatik harus dipertimbangkan.
KEYWORDS: CEA, cost-effectiveness analysis.
ChildTurcotte-Pugh Score, hepatic cirrhosis, hematemesismelena, vitamin K, transamin KATA KUNCI: CEA, cost-effectiveness analysis.
ChildTurcotte-Pugh Score, sirosis hepatik, hematemesis-melena, vitamin K, transamin Indones Biomed J.
: 43-50
alcoholic cirrhosis will develop esophageal varices after 2 years after being diagnosed, and 70-80% patients in 10 years.
About 25-35% patients with cirrhosis and large esophageal varices will experience variceal haemorrhage.
Acute variceal haemorrhage is a complication of cirrhosis which has life threatening impact.
, and acts as a major cause of death in cirrhosis patients.
The increase in portal pressure due to increased resistance to blood flow to the liver is largely due to the distortion of the liver structure to fibrous tissue and regenerative nodules and intra hepatic active vasoconstriction by 20% -30% of the increased intra hepatic resistance, and a decrease in endogenous production of nitric oxide.
One of the functions of the liver is to produce several clotting factors .
ncluding prothrombin and fibrinoge.
as well as to produce bile salts that are necessary for gastrointestinal absorption of vitamin K, which is needed to produce coagulation factor.
Deficiency in vitamin K can cause blood clotting disorders, to cause the patients to be prone to bleeding.
On the other hand, transamin .
ranexamic acid (TXA)), which is an antifibrinolytic agent, has proven useful for controlling bleeding in some conditions, especially is more favorable in small superficial lesions such as gastric erosion and in esophageal varices.
, and proven to provide cost-effectiveness in cirrhosis.
Neff et al.
had examined the economic impact of Introduction The liver is a major site of metabolism of various drugs.
patients with liver disease the liver capacity for metabolism/ elimination of drugs may be disturbed.
Cirrhosis of the liver .
epatic cirrhosi.
is one of the severe liver diseases that is chronic, irreversible, and causes high mortality.
, and this occupies the twelfth leading cause of death in the United States.
Hepatic cirrhosis is a diffuse process characterized by fibrosis and changes of the normal liver structure to abnormal nodule structure.
As a result, scar tissue is formed due to injury or long-term liver disease, and it causes the liver to fail its normal functions such as protein synthesis, cleaning process of the blood, resistance to infection, digesting foods, and energy storage.
The degree of severity of the liver disease can be divided into three categories with ChildTurcotte-Pugh (CTP) Score.
CTP Classification is a system used to classify the degree of liver damage or development of liver disease in hepatic cirrhosis patients.
There are some complications of cirrhosis such as ascites, hepatic encephalopathy (HE), hepatorenal syndrome.
SBP .
pontaneous bacterial peritoniti.
, and esophageal varices.
Fifty percent of patients with Table 1.
CTP Score.
Numerical Score Parameter Ascites None Slight Moderate / Severe Encephalopathy None Slight / Moderate Moderate / Severe Bilirubin .
g/dL) < 2.
> 3.
Albumin .
g/L) > 3.
< 2.
Prothrombin time .
econds, increase.
> 6.
Total Numerical Score CTP Class DOI: 10.
18585/inabj.
Cost Effectiveness Analysis of Hematemesis-Melena Treatment in Cirrhosis .
e Queljoe D) Indones Biomed J.
: 43-50
various regimens used for prophylaxis and treatment of cirrhosis-related complications, and found it necessary to evaluate the costs and complications of cirrhosis-related .
Cost-effectiveness analysis (CEA) used in accordance to the study objectives in assessing relationship between cost and outcome, which in this case is clinical outcome, and CEA is an important instrument in setting priorities for strategic planning of therapy.
By measuring and comparing cost and consequences of an intervention, efficient relationship could be assessed and the resources needed in the future could be estimated.
Methods This study was a non-experimental research and used the retrospective approach.
Data were obtained from adult patientsAo medical records which had major diagnosed hepatic cirrhosis cases.
In this study, the method used was CEA.
Therapeutic cost and consequences of therapy were measured and Research variables Dependent variables in this study were cost .
ost of vitamin K and combination of vitamin K-transami.
and clinical outcome .
uration of cessation of bleedin.
Independent variables in this study were type of treatment and CTP score.
Population and sample Population in this study was all the hospitalized hepatic cirrhosis patients with hematemesis-melena at Adi Husada Undaan Wetan Hospital, from January 2010 to December Patients were grouped based on their degree of liver disease with CTP score.
The number of samples was calculated based on formula.
N = p.
(Z1/2a/.
2 Z1/2 = minimum sample number = percentage proportion in first population group = percentage proportion in second population group = 1-p = degree of confidence coefficient in certain level of confidence .
xample 95 or 99%) = estimate percentage error possibility on number of sample determination .
1 or 0.
Calculation of sampleAos number in this study:
N = p.
(Z1/2a/.
2 = 0.
5 x 0.
5 x .
96/0.
2 = 24 patients Thus, the number of samples needed in each intervention group was 6 patients.
Inclusion and Exclusion Criteria Inclusion criteria in this study were hepatic cirrhosis patients with hematemesis-melena, adult age Ou 16 years .
, and patients treated with vitamin K or combination of vitamin K-transamin.
Exclusion criteria were patients who went home before the bleeding stopped, had not improved their clinical outcome, or died.
patients who had not recovered from bleeding.
patients with another kind of disease like hepatoma, or used another medication .
or example oral vitamin K or oral transami.
, which could interfere the treatment studied and outcome relationship.
patientAos medical record including diagnoses or clinical Data Analysis Techniques Data obtained were analyzed with statistical method.
First the normality of data was examined, then parametric (Anova one way, independent t-Test, and pooled t-Tes.
or non-parametric tests (Kruskal Wallis and Mann Whitney U tes.
were used to know the difference in duration of treatment until the bleeding stopped and the costs.
Degree of significance used for the tests was 0.
05 and the statistical program used was SPSS 17.
Besides, conclusions were also made using cost-effectiveness grid and average costeffectiveness ratio (ACER) calculation.
Calculation of ACER ACER was calculated based on the following formula.
ACER = cost / effectiveness.
Results Effectiveness was calculated based on the percentage of cumulative duration of treatment until improvement was less than or equal to 1 day in all patients and in patients with CTP Score A and B, as well as the duration of treatment to improve less than or equal to 3 days in patients with CTP Score C.
CTP Based on the effectiveness of therapy, in patients with CTP Score A found that vitamin K was more effective than vitamin K-effectiveness transamin although the difference was rather slight, in all patients and patients with CTP Score B and C, the effectiveness of vitamin K-transamin was greater than vitamin K.
While the cost of treatment was only calculated based on the average cost of the therapeutic use of vitamin K and vitamin K-transamin The Indonesian Biomedical Journal.
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based on the length of treatment to get better.
The higher the severity of liver cirrhosis, the longer the treatment will take and therefore contributes to the increasing number of drugs used to stop bleeding and will ultimately affect the cost of the used drugs.
Based on calculation with ACER, it showed that vitamin K was more cost-effective than vitamin K-transamin in all patients as well as patients with CTP Score A.
B, and C.
At the test time difference of improving the treatment of the samples using parametric and nonparametric methods Table 1.
Cost-Effectiveness Grid for CEA.
Cost of Alternative A Relative to Alternative B Effectiveness of Alternative A Relative to Alternative B Lower Equal Higher Higher .
/- .
rade of.
Equal Arbitrary Lower /- .
rade-of.
- .
Table 3.
Patients Cahracteristics Whole Group .
CTP Score A .
CTP Score B .
CTP Score C .
p value Gender, male 29 .
Gender, female 13 .
Age, years 12 A 13.
08 A 9.
80 A 15.
79 A 13.
Arterial systolic pressure, mmHg 62 .
Arterial diastolic pressure, mmHg Vitamin K 18 .
Vitamin K-Transamin 24 .
12,641 .
5,550 .
11,100 .
22,200 .
5,550 .
11,100 .
22,200 .
5,550 .
11,100 .
22,200 .
Therapy Cost Vitamin K (IDR) Vitamin K-Transamin (IDR) 62,643 .
44,975 .
53,970 .
86,737 .
44,975 .
53,970 .
86,737 .
44,975 .
53,970 .
86,737 .
Hospitalization duration 6 .
Duration of treatment to bleed stopped 5 .
Duration of treatment Data presented as mean standard deviation.
Significant difference if p O 0.
DOI: 10.
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Cost Effectiveness Analysis of Hematemesis-Melena Treatment in Cirrhosis .
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Table 4.
Patients Cahracteristics in CTP Score A.
B and C Patient Characteristics in CTP Score A Vitamin K .
Vitamin K-Transamin .
p value Gender, male 3 .
0,705
Gender, female 4 .
0,414
Age, years 64 A 10.
33 A 2.
0,034
Arterial systolic pressure, mmHg 33 .
Arterial diastolic pressure, mmHg 67 .
0,027
Hospitalized duration 4 .
Duration of treatment to bleed stopped 1 .
Duration of treatment
0,941
Cost 5,550 .
44,975 .
0,001
Vitamin K .
Vitamin K-Transamin .
p value Gender, male
0,109
Gender, female 1 .
%) 0 .
%) Age, years 52 A 21.
2 A 12.
0,323
Arterial systolic pressure, mmHg 87 .
Arterial diastolic pressure, mmHg 6 .
0,061
Hospitalization duration 6 .
0,107 Duration of treatment to bleed stopped 2 .
0,103 Duration of treatment
0,007
11,100 .
53,970 .
0,001
Vitamin K .
Vitamin K-Transamin .
p value Gender, male Gender, female 3 .
%) 3 .
67 A 19.
62 A 8.
0,801
Arterial systolic pressure, mmHg 88 .
0,022
Arterial diastolic pressure, mmHg 47 .
0,117
Hospitalized duration 11 .
0,134 Duration of treatment to bleed stopped 5 .
Duration of treatment
0,007
22,200 .
86,737 .
0,002
Patient Characteristics in CTP Score B Cost Patient Characteristics in CTP Score C Age, years Cost of analysis showed a significant difference (=0.
in comparison to the longer treatment improved in patients with CTP Score A.
B and C (Table .
Comparison of the lengths of time of treatment to improve in patients with vitamin K therapy in patients with CTP Score A and B were not significant, while comparison of the CTP Score A and C with B and C showed significant differences.
The duration lengths of treatment to improve therapy in patients with vitamin K-transamin in patients with CTP Score A and B were not significant, while in comparison the CTP Score A and C with B and C it showed significant differences (=0.
The result of the CTP Score, duration of treatment to improve the comparison between patients using vitamin K and vitamin K-transamin was not significant at the CTP Score A and B, while the CTP Score C results were significant (=0.
Based on the cost of the use of vitamin K only and vitamin K-transamin in the study samples, the result was a significant difference in comparison with the cost of treatment using vitamin K and vitamin K-transamin liver cirrhosis in patients with CTP Score A.
B, and C (Table The Indonesian Biomedical Journal.
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Table 5.
ACER in all patients.
Vitamin K
Vitamin K-transamin
IDR 12,641
IDR 62,643
44% cure rate
33% cure rate
Total Cost to treat all patients Effectiveness IDR 12,641 = IDR 28,731 ACER
IDR 62,643
= IDR 108,006
Table 6.
ACER in patients with CTP Score A.
B and C.
Vitamin K
Vitamin K-transamin
IDR 5,550
IDR 44,975
100% cure rate
33% cure rate
IDR 5,550
= IDR 5,550
IDR 44,975
= IDR 54,186
Total Cost to treat all patients IDR 11,100 IDR 53,970 Effectiveness 20% cure rate
70% cure rate
IDR 11,100
= IDR 55,500
IDR 53,970
= IDR 77,100
IDR 22,200
IDR 86,737
33% cure rate
100% cure rate
IDR 22,200
= IDR 67,272
IDR 86,737
= IDR 86,737
CTP Score
Total Cost to treat all patients Effectiveness ACER
ACER
Total Cost to treat all patients Effectiveness ACER Discussion One of the important pharmacistAos responsibilities in clinical pharmacy is to ensure good therapeutic outcome and pharmaceutical care which must not only be safe and effective, but also have a high value from economic and humanistic aspects.
In fact, pharmacy profession would not succeed in their role to provide pharmaceutical care without pharmaco-economic knowledge.
Therefore, pharmacoeconomic evaluation like CEA which compares cost and effectiveness of therapy is needed.
The cost of transamin is higher than the cost of vitamin K, and to know whether addition of transamin in vitamin K monotherapy is needed in clinical practice, cost-effectiveness evaluation is In this research, the cause of the incident of hematemesis-melena was not confirmed.
PVT is caused by increased hepatic resistance in cirrhosis, resulting in deterioration in the portal venous outflow, vascular micro thrombosis secondary to vascular ischemia and infarction may lead to the heart, with the loss of liver tissue .
arenchymal extinctio.
being replaced by fibrotic tissue.
The incident is most commonly caused by portal PVT that can contribute to significant morbidity and mortality.
Cirrhotic patients with PVT should be screened for varices and then anti coagulated with low-molecular-weight heparin for at least a 6-month period.
Newer evidence suggests that prophylactic anticoagulation in patients with cirrhosis may have a role in clinical management with decreased incidence of PVT and improved survival.
The patients characteristics can be seen in Table 3, while patients characteristics based on CTP classification can be seen in Table 4.
p value indicates significant difference if p O 0.
In this study, there was one group with a number of samples less than 6, and it was CTP score B group using vitamin K with just 5 subjects.
This was due to the limitation of hepatic cirrhosis patients with hematemesis-melena.
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Cost Effectiveness Analysis of Hematemesis-Melena Treatment in Cirrhosis .
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The difference of liver severity will take effect on therapeutic effectiveness.
The higher the liver damage, the lower the therapeutic effectiveness, due to decrease of liver function for coagulation factor synthesis .
, and if there is any hepatocellular disease or if the liver cell couldnAot synthesize blood coagulation factor, vitamin K given to patients wouldnAot be effective.
Beside CTP Score, there is another instrument used to classify the severity of the liver damage, which is a newer method called model of end stage liver disease (MELD).
There are some benefits of MELD, like no subjective assessment like CTP score .
scites, hepatic encephalopath.
, but hepatologists generally do not use MELD because not all laboratories use internationalized ratio (INR) which is one of MELD components as coagulation marker in hepatic cirrhosis patient, and there is no clear value limitation on MELD.
Besides that.
MELD scoring needs calculation, therefore quick and simple measurement couldnAot be .
In Indonesia, the biggest risk factor as the cause of hepatic cirrhosis progression of hepatitis C and B infections followed by hemochromatosis.
rather than alcohol, because of the difference between the amount of alcohol consumed by people in western countries than people in Indonesia.
The development of hepatitis C to hepatic cirrhosis usually take years or decades, with average of 20 years.
Most of hepatic cirrhosis patients are elderly people, usually in the range of 52-69 years old due to hepatic cirrhosis development which takes years or decades.
From this study it is known that hepatic cirrhosis symptoms appears averagely at the age of 51 years and culminates at the range of 52-69 years.
In this study bleeding mostly stopped at the first day after medication, although the patient had bled for days before hospitalized.
This is in accordance with literature that claims when vitamin K is given parenterally, prothrombin time (PT) may need 12 to 24 hours to normal, although improvement may happen in 1 to 2 hours.
, whereas transamin has t1/2 = 2 hours.
Therefore, it is most likely that patientAos bleeding could be stopped at the first day of Anti-fibrinolytic therapy has been shown to be useful in controlling bleeding in some conditions, especially in patients with gastric erosion and also in esophageal varices.
Anti-fibrinolytic effect is not associated with improved systemic fibrinolysis, but more due to the inhibition of local fibrinolysis in gastroduodenal mucosa.
Therefore, the use of transamin in addition to the use of vitamin K can be an option, but there is no sufficient evidence supporting a recommendation on the use of transamin in the treatment of gastrointestinal bleeding and bleeding from varices.
Regardless of the fact there is an evidence that transamin is a useful treatment for refractory bleeding due to gastric antral vascular ectasia in patients with cirrhosis.
Comparative pharmacoeconomics reviews, performed by calculating the percentage of patients with cirrhosis of the liver with hematemesis melena O 1 day in all patients and in patients with CTP Score A and B, as well as old treatment until the bleeding that stopped O 3 days in patients with CTP Score C.
Data were analyzed using cost-effectiveness grid and ACER.
From the cost-effectiveness in the table grid (Table .
it can be seen that vitamin K has a dominant outcome in patients with CTP Score A and trade off on all patients as well as patients with CTP Score B and C.
Consider further follow up on the results of the trade off is using ACER.
From the dominant finding in the results, it can be seen that treatment with vitamin K have a lower cost with higher effectiveness than vitamin K-transamin, so it can be concluded that vitamin K is more cost-effective than vitamin K-transamin.
Based on the calculation of ACER (Table 5 and .
, it showed the value of vitamin K was smaller than the vitamin K-transamin, so it can be concluded that vitamin K is more cost-effective than vitamin K-transamin in all patients as well as in patients with CTP Score A.
B, and C.
There are some limitations of this study including that of the number of samples which was too small, because it was taken from 1 hospital even in 2 years, and thatAos why the data were not homogenous and the distribution was not normal We recommend that in the future studies using more samples with a longer time span should be carried out so the samples can be homogeneous and have normal distribution.
The next limitation was the observed cost, in which this study only examined the cost of drugs, while other costs such as hospital and physician costs, laboratory costs, etc.
were not observed.
Another limitation was that the outcome of treatment was observed only until the bleeding stopped .
he duratio.
, other outcomes associated with bleeding such as PT was not observed.
PT is a laboratory test needed to evaluate blood coagulation rate.
Decrease of PT is an expected result from bleeding medication.
Conclusion The use of vitamin K therapy is more cost-effective than combination therapy of vitamin K-transamin in all patients with liver cirrhosis and hematemesis-melena, and in The Indonesian Biomedical Journal.
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patients with CTP score A.
B, and C.
This conclusion should be regarded with caution due to its limitation and further research is needed.
Suggestion is given for further research using a prospective design so that the results obtained can be representative of the actual condition of the patient and confounding variables can be better controlled so as to obtain a good study of the relationship between risk factors and effects.
In addition, the number of samples should be enlarged in order to get more homogeneous data and normal distribution, other components of cost such as cost of hospital, doctor, etc.
could be calculated, not only the cost of therapy vitamin K or vitamin K-transamin, and the outcome observed is not only of the duration of bleeding, but also Prothrombin Time, side effects, and other factors that affect bleeding in patients.
Acknowledgement This research was supported by the Research and Community Service Institution of the University of Surabaya (Lembaga Penelitan dan Pengabdian Kepada Masyarakat Ubay.
Surabaya.
References