Indian Journal of Vascular and Endovascular Surgery

ORIGINAL ARTICLE
Year
: 2022  |  Volume : 9  |  Issue : 4  |  Page : 287--290

Cost-effective treatment for deep-vein thrombosis in rural tertiary care hospital


Arunkumar Arasappa1, Nirmal Kumar1, M Anto2, GV Manoharan2, Duraipandian Selvanathan2,  
1 Department of Cardiothoracic and Vascular Surgery, Sri Manakula Vinayagar Medical College and Hospital, Puducherry, India
2 Department of General Surgery, Sri Manakula Vinayagar Medical College and Hospital, Puducherry, India

Correspondence Address:
Arunkumar Arasappa
Department of Cardiothoracic and Vascular Surgery, Sri Manakula Vinayagar Medical College and Hospital, Puducherry
India

Abstract

Objective: The aim was to compare the cost of treating deep-vein thrombosis (DVT) using unfractionated heparin (UFH) and low-molecular-weight heparin (LMWH) among patients in rural tertiary care hospitals. Materials and Methods: A retrospective study was conducted at a Rural Tertiary Care Hospital from April 2017 to April 2019. Fifty-four patients who had symptoms of swelling of the unilateral or bilateral lower limb with or without pain were subjected to Padua prediction score and Doppler study of both lower limbs. Confirmed cases of DVT were treated with UFH or LMWH. The cost of these two treatments was compared. Results: The mean cost of heparin was 2493.33 ± 1406.27 Indian rupee (INR) in the study population. The mean cost of LMWH was 13,520 ± 9806.35 (INR) in the study population. There was a statistically significant difference between UFH and LMWH with regard to the cost of drugs (INR) for treatment (P < 0.001), which indicated that UFH was a cost-effective treatment compared to LMWH. Conclusions: The study's findings prove that UFH is a cost-effective treatment compared to LMWH in Rural Tertiary Care Hospitals for DVT. Based on the patient's affordability, the treatment decision can be made.



How to cite this article:
Arasappa A, Kumar N, Anto M, Manoharan G V, Selvanathan D. Cost-effective treatment for deep-vein thrombosis in rural tertiary care hospital.Indian J Vasc Endovasc Surg 2022;9:287-290


How to cite this URL:
Arasappa A, Kumar N, Anto M, Manoharan G V, Selvanathan D. Cost-effective treatment for deep-vein thrombosis in rural tertiary care hospital. Indian J Vasc Endovasc Surg [serial online] 2022 [cited 2022 Nov 28 ];9:287-290
Available from: https://www.indjvascsurg.org/text.asp?2022/9/4/287/360540


Full Text



 Introduction



Deep-vein thrombosis (DVT) is one of the common vascular diseases causing morbidity and mortality.[1] DVT is defined as the development of thrombosis within the deep veins of the pelvis or lower limbs.[2] Vessel endothelium injury causes sluggish blood flow, which promotes blood clot formation and thereby reducing the venous blood flow, and in complicated cases can result in pulmonary embolism as the thrombi dislodge from the deep veins and move to the lungs through the vascular system.[3] DVT causes a substantial financial burden on the health-care system as well as the patients. This burden of cost is due to its acute episodes, long-term morbidities, frequent recurrence, and overall loss of patient productivity.[4],[5] Venous thromboembolism (VTE) is one of the preventable causes of morbidity and death in hospitalized patients, especially in intensive care units. Almost 25% of all VTE patients are associated with hospitalization,[6],[7] and 50%–75% in hospitalized patients occur in those in the medical wards.[8],[9]

Unfractionated heparin (UFH) is less expensive but must be given at least twice daily, whereas low-molecular-weight heparins (LMWHs) and fondaparinux are more costly but can be given once daily.[10] All three agents are effective in reducing the risk of VTE in randomized trials.[11] DVT is usually seen in patients who have sedentary habits, obesity, prolonged bedridden states, following major orthopedic, or gynecology surgery (after prolonged surgery duration). DVT can also occur in patients receiving chemotherapy for malignant conditions, renal failure, and in patients with coagulation disorders such as protein C and protein S deficiency. The fundamental pharmacological approach in patients with DVT is to start with parenteral anticoagulants, either LMWH or UFH, followed by long-term Vitamin K antagonists. Beginning parenteral anticoagulation in the acute phase is recommended before diagnostic tests for intermediate to high-risk DVT patients.[12]

In the United States, DVT is associated with a projected initial hospitalization cost of $9805.[13] Daily mean expenditure accounts for $1594 for the initial episodes,[14] and an estimated annual cost for treatment ranging from $4.9 to $7.5 billion.[15] There is no study available from India to date on the cost of DVT treatment. Hence, this study was conducted to fill in this lacuna and to compare the treatment cost of UFH with LMWH among patients admitted to Rural Tertiary Care Hospitals.

 Materials and Methods



Participants and study design

This retrospective study was undertaken in the Department of Cardiovascular and Thoracic Surgery in a Rural Tertiary Care Hospital from April 2017 to April 2019. Ethical approval was obtained from the Institutional Ethics Committee, and data confidentiality was maintained. All patients who had symptoms of swelling of the unilateral or bilateral lower limb with or without pain were subjected to Padua prediction scoring and bilateral lower limb Doppler studies. Patients with a confirmed diagnosis of DVT of the lower limb were included in the study. These patients were treated either with UFH or with LMWH.

The patient was treated with UFH 5000 IU IV 6th hourly and monitored with activated partial thromboplastin time (aPTT). The aPTT was kept at two and half times the control value to achieve the therapeutic level. The patient was started with orally acting direct anticoagulants tablet dabigatran 110 mg BD after 48 h of beginning heparin following the standard protocol. The patient's lower limb elevation with pillows was followed. We never used Thrombo-Embolus Deterrent stockings for established cases of DVT. The patient was not mobilized for at least 7 days except for routine purposes. Ultrasound Doppler was repeated on the 7th day of starting the injectable heparin. If the patient had only partially recanalized venous lumen, the dose was continued for 3 more days. If lumen was fully not recanalized, the dose was continued for a further 7 days. All patients were continued with tablet dabigatran for 6 months, even after recanalization to achieve full luminal clearance of thrombus. UFH was used for maximum period of 7 days (extended in cases to achieve partial lumen clearance) by which time clot resolution usually starts. Only 10 pts received the extended period of UFH for more than 15 days. Its usual practice to start dabigatran after starting heparin and is used as a continuation drug to prevent relapses. Prolonged heparin usage is not recommended in any protocol and has its own complications and hence the usage of dabigatran. The cost of the treatments was collected from the hospital database and compared. The grouping of the patients was done based on the financial ability of the patient to afford care. Due to this reason, there is unequal distribution of patients in both the study arms.

Sample size calculation

The sample size was calculated assuming the expected mean and standard deviation of the cost of the drug in UFH as/, σ1(7830.8, 500) and in the low molecular weight, heparin as/, σ0(8373.1, 500), as per the previous study by Ahmad et al.[16] Power of study 90% and 5% two-sided alpha error were considered. Formula, as proposed by Kirkwood, was used for calculation.[17] The required sample size as per the above-mentioned calculation and considering the 2:1 ratio was 28 and 14 in Group 1 and Group 2, respectively. To account for a nonparticipation rate/loss to follow up rate of about 10%, another two subjects for Group 1 and one subject for Group 2 were added to the sample size. Hence, the final required sample size was 30 and 15 in Group 1 and Group 2, respectively.

Statistical methods

The cost of heparin was considered as the primary outcome variable. Type of heparin and duration of hospital stay was considered as primary explanatory variables. Mean and standard deviation was done for descriptive. Independent sample t-test (2 Groups) was used for comparison. For nonnormally-distributed quantitative parameters, medians and interquartile range were compared between the study groups using the Mann–Whitney U-test (2 Groups). Statistical significance was taken with a P < 0.05. coGuide was used for the statistical analysis.[18]

 Results



The final analysis included 54 patients.

[Table 1] depicts the two study groups and the patient distribution, which shows that the majority (72.23%) of the patients were treated with UFH, and 27.77% were treated with LMWH.{Table 1}

There was no statistically significant difference in mean age (in years) between the type of heparin (P > 0.05). The difference in the proportion of different age groups between the types of heparin was found to be insignificant, with a P = 0.850. The majority of 17 (43.58%) people aged between 41 and 60 years were on injection enoxaparin. The difference in the proportion of males and females between the types of heparin was insignificant with the P = 0.636 with the majority of 21 (53.84%) male participants on heparin 7 (46.67%) males were on injection enoxaparin. The difference in the proportion of duration of hospital stay between the types of heparin was found to be insignificant with the P = 0.794 [Table 2].{Table 2}

There was a statistically significant difference between heparin and LMWH with regard to the cost of drugs Indian rupee (INR) for treatment [P < 0.001, [Table 3]].{Table 3}

As the cost price of UFH and LMWH varies with various brands of it, only an approximate value could be used for evaluation. On an average, UFH was costing 800 Rs./day and LMWH was costing us 1400 Rs./day. The cost was calculated based on a duration of 7–10 days on an average in both the arms and was statistically significant.

 Discussion



This retrospective study on 54 patients with DVT showed that heparin (2493.33 ± 1406.27 INR) was a cost-effective treatment for DVT when compared to LMWH (13,520 ± 9806.35 INR). Among the 54 patients studied, the majority were in the age group of 41–60 years. The duration of hospital stay ranged from 6 to 16 days.

The LMWHs show superior effectiveness over UFH in many clinical settings, and specifically in the management of DVT. LMWHs also cause fewer adverse effects; they are less likely to produce heparin-induced thrombocytopenia and bleeding manifestations. The high procurement costs of LMWHs in developing countries are compensated by reduced costs for monitoring and decreased costs of management of adverse effects.[19]

Both UFH and LMWHs have recognized roles in the prevention and treatment of VTE and as adjuvant therapy for atherothrombotic syndromes.[20],[21] LMWHs are replacing UFH for therapeutic anticoagulation due to several advantages, such as a more predictable pharmacokinetic profile and ease of use.[22],[23] Even though their antithrombotic effects are similar, the LMWHs are heterogeneous compounds produced by different processes and have distinct biochemical and pharmacological properties.[24] This diversity among the LMWHs has important implications for clinical practice. The continual pressure on pharmacy budgets has resulted in initiatives to reduce costs by switching to the lowest price. A randomized controlled trial on the efficacy of UFH versus LMWH in thrombo-prophylaxis by Ishi et al.[25] shows low doses UFH is as effective as LMWH as a prophylactic agent for VTE in medically ill patients.

A cost-effectiveness study by Gordois et al.,[10] on patients undergoing orthopedic surgeries on heparin, showed that compared to enoxaparin, fondaparinux was cost-effective to the patient as well as the health-care system. Fondaparinux saved 27 euros/patient in 5 years. Therefore, by comparing with enoxaparin, Fondaparinux was a cost-effective strategy.[10] A similar study among Serbian patients revealed that enoxaparin was a cost-effective strategy (from 5322.97 Serbia and Montenegro dinars [CSD]) per quality-adjusted life-year gained when used in outpatients, to 10,929.76 CSD per quality-adjusted life-year gained when used in inpatients).[26]

Similar to these studies, the current study also shows that the UFH is more cost-effective in low-resource settings compared to LMWH. Hence, the UFH can be used as a cost-effective method without any compromise in the therapeutic properties. The limitation of the current study is that it is a single-center experience in a relatively small sample. Multicentric studies involving various tiers of hospital settings are recommended in the future.

 Conclusions



This study showed that UFH is a cost-effective drug compared to LMWH. Hence, in resource-poor settings such as in India, UFH can be used effectively to treat DVT.

Acknowledgments

We acknowledge the technical support in data entry, analysis, and manuscript editing by “Evidencian Research Associates.”

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

1Goldhaber SZ, Bounameaux H. Pulmonary embolism and deep vein thrombosis. Lancet 2012;379:580-95.
2Caldeira D, Rodrigues FB, Barra M, Santos AT, de Abreu D, Gonçalves N, et al. Non-vitamin K antagonist oral anticoagulants and major bleeding-related fatality in patients with atrial fibrillation and venous thromboembolism: A systematic review and meta-analysis. Heart 2015;101:1204-11.
3Yang SD, Ding WY, Yang DL, Shen Y, Zhang YZ, Feng SQ, et al. Prevalence and risk factors of deep vein thrombosis in patients undergoing lumbar interbody fusion surgery: A single-center cross-sectional study. Medicine (Baltimore) 2015;94:e2205.
4Raskob GE, Angchaisuksiri P, Blanco AN, Buller H, Gallus A, Hunt B, et al. Thrombosis: A major contributor to global disease burden. Thromb Res 2014;134:931-8.
5Dobesh PP. Economic burden of venous thromboembolism in hospitalized patients. Pharmacotherapy 2009;29:943-53.
6Collaborative overview of randomised trials of antiplatelet therapy-III: Reduction in venous thrombosis and pulmonary embolism by antiplatelet prophylaxis among surgical and medical patients. Antiplatelet Trialists' Collaboration. BMJ 1994;308:235-46.
7Heit JA, Silverstein MD, Mohr DN, Petterson TM, O'Fallon WM, Melton LJ 3rd. Risk factors for deep vein thrombosis and pulmonary embolism: A population-based case-control study. Arch Intern Med 2000;160:809-15.
8Goldhaber SZ, Dunn K, MacDougall RC. New onset of venous thromboembolism among hospitalized patients at Brigham and Women's Hospital is caused more often by prophylaxis failure than by withholding treatment. Chest 2000;118:1680-4.
9Goldhaber SZ, Tapson VF, DVT FREE Steering Committee. A prospective registry of 5,451 patients with ultrasound-confirmed deep vein thrombosis. Am J Cardiol 2004;93:259-62.
10Gordois A, Posnett J, Borris L, Bossuyt P, Jönsson B, Levy E, et al. The cost-effectiveness of fondaparinux compared with enoxaparin as prophylaxis against thromboembolism following major orthopedic surgery. J Thromb Haemost 2003;1:2167-74.
11Francis CW. Clinical practice. Prophylaxis for thromboembolism in hospitalized medical patients. N Engl J Med 2007;356:1438-44.
12Kearon C, Akl EA, Comerota AJ, Prandoni P, Bounameaux H, Goldhaber SZ, et al. Antithrombotic therapy for VTE disease: Antithrombotic therapy and prevention of thrombosis, 9th ed.: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012;141:S419-96.
13Spyropoulos AC, Lin J. Direct medical costs of venous thromboembolism and subsequent hospital readmission rates: An administrative claims analysis from 30 managed care organizations. J Manag Care Pharm 2007;13:475-86.
14Dasta JF, Pilon D, Mody SH, Lopatto J, Laliberté F, Germain G, et al. Daily hospitalization costs in patients with deep vein thrombosis or pulmonary embolism treated with anticoagulant therapy. Thromb Res 2015;135:303-10.
15Mahan CE, Borrego ME, Woersching AL, Federici R, Downey R, Tiongson J, et al. Venous thromboembolism: Annualised United States models for total, hospital-acquired and preventable costs utilising long-term attack rates. Thromb Haemost 2012;108:291-302.
16Ahmad A, Patel I, Asani H, Jagadeesan M, Parimalakrishnan S, Selvamuthukumaran S. A comparison of enoxaparin with unfractionated heparins in patients with coronary heart disease in an emergency department in rural South Indian tertiary care teaching hospital. Indian J Pharmacol 2015;47:90-4.
17Kirkwood BT. Essentials of Medical Statistics. 2nd ed. London: Blackwell Scientific Publications; 1988. p. 234.
18BDSS Corp. Released 2020. coGuide Statistics Software, Version 1.0. India: BDSS Corp.; 2020. Available from: https://www.coguide.in. [Last accessed on 2022 Apr 05].
19Jones TE, Smith BJ, Polasek JF. Pharmacoeconomics of low-molecular-weight heparins: Limitations of studies comparing them to unfractionated heparin. Expert Opin Pharmacother 2004;5:1887-97.
20Geerts WH, Bergqvist D, Pineo GF, Heit JA, Samama CM, Lassen MR, et al. Prevention of venous thromboembolism: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 2008;133:381S-453S.
21Anderson JL, Adams CD, Antman EM, Bridges CR, Califf RM, Casey DE Jr., et al. ACC/AHA 2007 guidelines for the management of patients with unstable angina/non-ST-Elevation myocardial infarction: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines for the Management of Patients With Unstable Angina/Non-ST-Elevation Myocardial Infarction) developed in collaboration with the American College of Emergency Physicians, the Society for Cardiovascular Angiography and Interventions, and the Society of Thoracic Surgeons endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation and the Society for Academic Emergency Medicine. J Am Coll Cardiol 2007;50:e1-157.
22Dolovich LR, Ginsberg JS, Douketis JD, Holbrook AM, Cheah G. A meta-analysis comparing low-molecular-weight heparins with unfractionated heparin in the treatment of venous thromboembolism: Examining some unanswered questions regarding location of treatment, product type, and dosing frequency. Arch Intern Med 2000;160:181-8.
23Hirsh J, Bauer KA, Donati MB, Gould M, Samama MM, Weitz JI. Parenteral anticoagulants: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 2008;133:141S-59S.
24Merli GJ, Vanscoy GJ, Rihn TL, Groce JB 3rd, McCormick W. Applying scientific criteria to therapeutic interchange: A balanced analysis of low-molecular-weight heparins. J Thromb Thrombolysis 2001;11:247-59.
25Ishi SV, Lakshmi M, Kakde ST, Sabnis KC, Jagannati M, Girish TS, et al. Randomised controlled trial for efficacy of unfractionated heparin (UFH) versus low molecular weight heparin (LMWH) in thrombo-prophylaxis. J Assoc Physicians India 2013;61:882-6.
26Jankovic SM, Milovanovic DR. Cost and utility of a low-molecular-weight heparin and unfractionated heparin for treatment of deep venous thrombosis in a Balkan country: A model analysis. Exp Clin Cardiol 2006;11:111-6.