Prescribing Pattern and Risk Analysis of Potential Significant Drug Interactions among Warfarin Users in Taiwan: A National Health Insurance Research Database Study
Date Issued
2010
Date
2010
Author(s)
Chen, Ya-Ting
Abstract
Background:
Warfarin exhibits narrow therapeutic range and high protein binding. It is metabolized via cytochrom P450 enzyme system. Therefore, patients treated with warfarin are prone to serious drug-drug interactions (DDIs) and major adverse events (AEs). DDI of warfarin is significantly associated with 1.2~4.5 times increased risk of major hemorrhage, hospital admission, and prolonged length of stay. However, the occurrence of DDIs and AEs during warfarin therapy has not been studied extensively among Asian population. Few studies used national database, and definitions and lists of DDIs varied in the literature.
Objectives:
Using Taiwan’s National Health Insurance Research Database to analyze the prescription pattern of warfarin, prevalence rate of potential significant DDIs, incidence rate (IR) of major AEs (i.e., hemorrhage and thromboembolism) among warfarin users in Taiwan.
Methods:
The National Health Insurance Research Database with one million randomly selected individuals in Taiwan was used in this retrospective cohort study. New users started warfarin between April 1997 and December 2004. Prescribing pattern, including prescribed daily warfarin dose and average PT/INR (prothrombin time/international normalized ratio) monitoring frequency, were analyzed.
DDIs were defined as prescriptions from outpatient clinics with at least one day overlap with warfarin treatment episodes. Significance grade one DDIs were defined as DDIs with major severity and established documentation. A total of 56 grade one DDIs were evaluated in this study. In addition, dose of warfarin and PT/INR monitoring frequency when DDIs occurred were compared with those without grade one DDIs.
Major adverse events were defined as the first emergency room visits and/or hospitalizations with a diagnosis of hemorrhage or thromboembolism, identified by International Classification of Disease, Ninth Revision, Clinical Modification (ICD9-CM), during the treatment episode. Moreover, all thromboembolism events were confirmed by antithrombotic agents and primary indications for warfarin.
Results:
Among 4047 new-users, mean age was 63.4 years old. More than half (56.3%) of new-users were female. Warfarin was prescribed mainly for ischemic heart disease (23.2%). The most common comobidity was hypertension (36.4%). Average daily dose of warfarin was 2.8 ±1.2 mg. There were 29.1% of patients never received PT/INR monitoring during warfarin treatment. Other patients monitored PT/INR every 40.5 days.
A total of 2582 warfarin users (63.8%) were concurrently prescribed drugs with grade 1 DDIs. The most frequently prescribed medicines were aspirin (34.5%), noscapine (11.1%), amiodarone (9.4%), ketoprofen (7.4%), and naproxen (7.2%). Approximately 70% of these prescriptions were from the same physicians. About half of DDIs (54.4%) were from the medical centers. Doses of warfarin with or without DDIs were similar (p = 0.114). About half of patients (44.6%) had no PT/INR monitoring orders during DDIs. Fewer patients checked PT/INR when DDIs were involved different physicians.
There were 412 patients developing hemorrhage with an incidence rate of 10.9% per person-year, and the majority was gastrointestinal hemorrhage (40.8%). On the other hand, 474 patients experiencing thromboembolism with an incidence rate of 12.8% per person-year, and the most common diagnosis was ischemic stroke (31.4%).
Conclusions:
Average daily warfarin dose was 2.8 mg. Approximately 30% of patients had no PT/INR monitoring during treatment. PT/INR was ordered about every 6 weeks. Prevalence of grade one DDIs were more than 60%. The most prevalent DDIs were aspirin, noscapine, amiodarone. Almost half of patients had no PT/INR monitoring orders during DDIs. Moreover, IRs of hemorrhage and thromboembolism were 10.9%, 12.8% per person-years, respectively. The most common major AEs were gastrointestinal hemorrhage and ischemic stroke. In Taiwan, medical records from different physicians have not yet been completely retrieved through medical insurance cards. Computerized DDI alert systems are uncommon in hospitals. It is essential to establish a computerized electronic alert system on DDIs along with continuing educations for physician and pharmacist to safeguard patients’ safety.
Subjects
prescribing pattern
drug interaction
drug adverse event
National Health Insurance Research Database
Type
thesis
File(s)![Thumbnail Image]()
Loading...
Name
ntu-99-R96451010-1.pdf
Size
23.32 KB
Format
Adobe PDF
Checksum
(MD5):3ad5939a396e54fceb357cd732078ddd