|Year : 2014 | Volume
| Issue : 3 | Page : 105-108
A comparison of warfarin utilisation in North America and Ireland
Hussein Haji1, Kyle Wilby2, Muhammad Mamdani3
1 College of Pharmacy, Dalhousie University, Halifax, Nova Scotia, Canada
2 College of Pharmacy, Qatar University, Doha, Qatar
3 Applied Health Research Centre of the Li Ka Shing Knowledge Institute of St. Michael's Hospital, Toronto, Ontario; Institute for Health Policy, Management and Evaluation, Faculty of Medicine and Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada
|Date of Web Publication||31-Jul-2014|
Applied Health Research Centre of the Li Ka Shing Knowledge Institute of St. Michael's Hospital, University of Toronto Faculty of Medicine and Leslie Dan Faculty of Pharmacy, 30 Bond St. Toronto, ON M5B 1W8, Canada
Background: The objective of this study was to compare warfarin utilisation trends in Canada, the United States, and Ireland between January 2005 and September 2011.
Materials and Methods: We conducted a population-based cross-sectional time series analysis of warfarin utilisation data from January 2005 to September 2011 in the United States, Canada, and Ireland to examine differences in temporal trends in warfarin utilisation.
Results: A nearly 50% higher warfarin utilisation rate was observed in Canada and Ireland relative to the United States - the average monthly warfarin utilisation rate was approximately 626 units per 1,000 people in Canada, 423 units per 1,000 people in the United States, and 630 units per 1,000 people in Ireland. However, relative rates of growth in warfarin utilisation were 25.1%, 15.3%, and 38.3% for the United States, Canada, and Ireland, respectively.
Interpretation: Rates of warfarin utilisation differ considerably and geographically as evidenced by utilisation rates in the United States, Canada, and Ireland.
Keywords: Ireland, North America, utilisation trends, warfarin
|How to cite this article:|
Haji H, Wilby K, Mamdani M. A comparison of warfarin utilisation in North America and Ireland. J Health Spec 2014;2:105-8
| Introduction|| |
The prevalence of thromboembolic related conditions is progressively increasing as countries such as the United States continue to experience significant growth in increasingly ageing and sedentary populations.  This increase in the incidence of thromboembolic conditions will facilitate expansion in utilisation of antithrombotic agents such as warfarin and other oral anticoagulants.
Warfarin is the most commonly used oral anticoagulant worldwide.  Its use dates back to the 1920s although it was approved for therapeutic use in the United States in 1954.  On the other hand, newer oral anticoagulants such as dabigatran, rivaroxaban, and apixaban have only been available for a fraction of this time.  For example, dabigatran has been available in the United States since only October 2010.  These newer agents possess certain advantages over warfarin, especially the lack of required international normalized ratio (INR) monitoring.  INR is a measure of the blood's ability to clot; it is an important monitoring parameter used to determine the efficacy of warfarin therapy for a specific patient.  However, the newer anticoagulant agents also have certain disadvantages when compared with warfarin, namely the availability of long-term safety data. 
Moreover, a wealth of information exists detailing the pharmacology of warfarin and the multinational epidemiology of the conditions for which warfarin is used to prevent or treat. ,, For example, epidemiological research has revealed that the prevalence of atrial fibrillation, a major disorder requiring long-term anticoagulation, is approximately 5% in Americans over the age of 65 and between 2.5 - 5% in the United Kingdom. , While warfarin remains the mainstay of anticoagulant treatment globally, very little information is available comparing warfarin utilisation between countries. The objective of this study was to examine temporal trends in warfarin utilisation in Canada, United States, and Ireland.
| Materials and Methods|| |
We conducted a population-based cross-sectional time series analysis of warfarin utilisation data from January 2005 to September 2011 in the United States, Canada, and Ireland to examine differences in temporal trends in warfarin utilisation. These three countries were selected due to the availability of data. The data was obtained from IMS Health Inc, which tracks over 80% of global prescription sales of over 1.3 million products.  This research study was approved by the ethics review board at Qatar University, Doha, Qatar.
Warfarin utilisation rates for each of the three countries were calculated per 1,000 people using monthly population estimates acquired from the World Bank public data.  The primary outcome measure of the study was the monthly number of warfarin units used per 1,000 people for each of the three countries. One unit of warfarin was defined as one tablet of warfarin. The primary outcome measure of the study was calculated by taking the number of units (tablets) of warfarin used in a country during a specific month and the country's population for that month as reported by the World Bank public data, then dividing the former by the latter, and then multiplying the result by 1,000. Following calculation of the primary outcome measures, the average monthly warfarin utilisation rate for each of the three countries included in the study was determined by taking the average of the primary outcome measures for the specific country. Time series analysis was used to examine temporal trends in warfarin utilisation. 
| Results|| |
A nearly 50% higher warfarin utilisation rate was observed in Canada and Ireland relative to the United States - the average monthly warfarin utilisation rate was approximately 626 units per 1,000 people in Canada, 423 units per 1,000 people in the United States, and 630 units per 1,000 people in Ireland [Figure 1]. However, relative rates of growth in warfarin utilisation were 25.1% (from 376.65 units per 1,000 people in January 2005 to 471.15 units per 1,000 people in September 2011), 15.3% (from 548.53 to 632.66 units per 1,000 people over the study timeframe), and 38.3% (from 513.72 to 710.35 units per 1,000 people over the study timeframe) for the United States, Canada, and Ireland, respectively.
|Figure 1: Warfarin utilisation rates in the U.S., Canada, and Ireland from January 2005 to September 2011|
Click here to view
The findings of our study suggest significant differences in warfarin utilisation rates among the three countries examined. First, Canada and Ireland, which were almost equal in terms of average monthly warfarin utilisation rates, and both countries displayed higher warfarin utilisation rates than the United States. Although these rates were similar in Canada and Ireland, Ireland's relative rate of growth in warfarin utilisation was more than double that of Canada. Canada had the lowest relative rate of growth in warfarin utilisation. Therefore, Ireland had both the highest warfarin utilisation rate as well as the highest relative rate of growth.
These observations may be partly driven by the recent introduction of generic warfarin in Ireland in July 2008.  Generic warfarin is more affordable than the newer brand name anticoagulants and is publically reimbursed in Ireland.  The cost of 100 tablets of warfarin, available as generic Teva-Warfarin in Ireland, ranges from €3.79 for 1 mg to €8.75 for 5 mg.  The 10 mg strength of warfarin is not available in Ireland.  On the other hand, the newer anticoagulants, including dabigatran (Pradaxa), rivaroxaban (Xarelto), and apixaban (Eliquis), are only available as brand name products and are significantly more costly: The cost of 60 capsules of either 75 mg, 110 mg, or 150 mg of Pradaxa is €73.73, the cost of 60 tablets of Xarelto is €363.56 for the 10 mg strength, and the cost of 60 tablets of Eliquis is €102.71 for the 2.5 mg strength.  Clearly, upon considering the vastly varying costs of warfarin versus the newer oral anticoagulants in Ireland, the observation that Ireland had the highest warfarin utilisation rate as well as the highest relative rate of growth in warfarin use becomes reasonable and somewhat predictable.
Further, it is important to note that a lesser but still significant price variation between warfarin and the newer oral anticoagulants also exist in the United States and Canada. In the United States, the cost of 100 tablets of generic warfarin ranges from USD $58.34 for the 1 mg strength to $98.56 for the 10 mg strength, the cost of 60 capsules of Pradaxa is USD $349.99 for both 75 mg and 150 mg strengths, the cost of 90 tablets of Xarelto is USD $1,030.86 for 10 mg, 15 mg, and 20 mg strengths, and the cost of 60 tablets of Eliquis is USD $349.99 for both the 2.5 mg and 5 mg strengths.  As the difference in cost between warfarin and the newer anticoagulants is comparably not as significant as in Ireland, it is possible that this may explain the lower usage trends and growth rates of warfarin in the United States and Canada. Also supporting the observed trends is the fact that there was earlier introduction and increasing utilisation of newer anticoagulants, such as dabigatran and rivaroxaban, as alternatives to warfarin in the United States and Canada relative to Ireland. ,, Whereas dabigatran and rivaroxaban were introduced in Canada in July 2008 and September 2008, respectively and in the United States in October 2010 and July 2011 respectively, only dabigatran was introduced in Ireland during the study timeframe. ,, Rivaroxaban was introduced in Ireland in December 2011, three months following the last month included in the study.  Regardless, we observed considerable regional differences well before the introduction of the newer oral anticoagulants to the global markets.
The primary limitation of the study was the limited nature of the available data. The data lacked accompanying clinical details including patient demographics and indications for warfarin use, although these data were not required for the purpose of this study. A second limitation may have been the inclusion of only one European country due to the availability of data. Future studies may benefit from including a variety of European countries, which may enrich data analysis and comparison. Lastly, the study was limited by the lack of availability of data pertaining to newer oral anticoagulants.
| Conclusion|| |
Overall, as determined by data analysis and interpretation, rates of warfarin utilisation in the United States, Canada, and Ireland differ considerably. This study provides a solid baseline analysis but future studies should focus on the impact of newer anticoagulants on warfarin usage trends. As prescribing and utilisation of these newer agents becomes more common, the true impact of newer anticoagulants on rates of warfarin usage will become more evident. The results of this study will provide a foundation for future examination of cross-national anticoagulant utilisation.
| References|| |
|1.||Neidecker M, Patel AA, Nelson WW, Reardon G. Use of warfarin in long-term care: A systematic review. BMC Geriatr 2012;12:14. |
|2.||Pirmohamed M. Warfarin: Almost 60 years old and still causing problems. Br J Clin Pharmacol 2006;62:509-11. |
|3.||Drugs@FDA database. U.S. Food and Drug Administration. 2013. Available from: http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm. [Last accessed on 2013 Jul 30]. |
|4.||Lexicomp. 2013. Available from: http://online.lexi.com.ezproxy.library.dal.ca/lco/action/doc/retrieve/docid/patch_f/3891003 [Last accessed on 2013 Aug 21]. |
|5.||Adam SS, McDuffie JR, Ortel TL, Williams JW Jr.. Comparative effectiveness of warfarin and new oral anticoagulants for the management of atrial fibrillation and venous thromboembolism: A systematic review. Ann Intern Med 2012;157:796-807. |
|6.||Mukherjee D, Patil CG. Epidemiology and the global burden of stroke. World Neurosurg 2011;76(6 Suppl):S85-90. |
|7.||The World Health Organization MONICA Project (monitoring trends and determinants in cardiovascular disease): A major international collaboration. WHO MONICA Project Principal Investigators. J Clin Epidemiol 1988;41:105-14. |
|8.||Acute Atrial Fibrillation. Best Practice. 2013. Available from: http://bestpractice.bmj.com.ezproxy.library.dal.ca/best-practice/monograph/3/basics/epidemiology.html. [Last accessed on 2013 Sept 11]. |
|9.||Prystowsky EN, Benson DW Jr, Fuster V, Hart RG, Kay GN, Myerburg RJ, et al. Management of patients with atrial fibrillation. A Statement for Healthcare Professionals. From the Subcommittee on Electrocardiography and Electrophysiology, American Heart Association. Circulation 1996;93:1262-77. |
|10.||IMS Health Inc. IMS Web site. 2013. Available from: http://www.imshealth.com. [Last accessed on 2013 Aug 21]. |
|11.||Countries and Economies. The World Bank. 2013. Available from: http://data.worldbank.org/country. [Last accessed on 2013 Aug 21]. |
|12.||Helfenstein U. Box-Jenkins modeling in medical research. Stat Methods Med Res 1996;5:3-22. |
|13.||Human Medicines Products List. Irish Medicines Board. 2013. Available from: http://www.imb.ie/EN/Medicines/HumanMedicines/HumanMedicinesListing.aspx [Last accessed on 2013 Jul 30]. |
|14.||Updates to the List of Reimbursable Items and High Tech Scheme List. Health Service Executive. 2014. Available from: http://www.hse.ie/eng/staff/PCRS/items/ [Last accessed on 2014 May 23]. |
|15.||Drug Product Database. Health Canada. 2013. Available from: http://webprod5.hc-sc.gc.ca/dpd-bdpp/index-eng.jsp [Last accessed on 2013 Jul 30]. |