Thrombosis Research 133 (2014) 550–554
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Regular Article
Knowledge, satisfaction, and concerns regarding warfarin therapy and their association with warfarin adherence and anticoagulation control Ye Wang a, Ming Chai Kong b, Lai Heng Lee c, Heng Joo Ng c, Yu Ko a,⁎ a b c
Department of Pharmacy, Faculty of Science, National University of Singapore, Singapore Department of Pharmacy, Singapore General Hospital, Singapore Department of Haematology, Singapore General Hospital, Singapore
a r t i c l e
i n f o
Article history: Received 8 October 2013 Received in revised form 20 December 2013 Accepted 3 January 2014 Available online 7 January 2014 Keywords: Anticoagulant Concerns Knowledge Medication adherence Satisfaction Warfarin
a b s t r a c t Introduction: A better understanding of patients’ knowledge, satisfaction and concerns can identify deficits and help develop targeted patient education. This study aimed to examine patients’ knowledge, satisfaction and concerns regarding warfarin therapy and assess their association with warfarin adherence and international normalized ratio (INR) control. Materials and methods: A cross-sectional survey was conducted in a convenience sample of patients taking warfarin in an anticoagulation clinic. The questionnaire consisted of questions on patients’ knowledge, satisfaction and concerns regarding warfarin treatment. Patients’ warfarin refill records and time within the therapeutic INR range were retrieved from hospital databases. Results: One hundred and eighty-three patients participated in the survey. Patients had inadequate knowledge of warfarin-diet and warfarin-drug interactions. Over 40% of the respondents were not satisfied with the waiting time to see a pharmacist. The most common concerns of taking warfarin were worries about warfarin-drug interactions (36.1%), forgetting to take warfarin (26.2%) and worries about side effects (25.7%). Higher satisfaction was associated with better knowledge (r = 0.24, p = 0.001) and fewer concerns (rs = − 0.23, p = 0.002). Better knowledge and higher satisfaction were associated with higher warfarin adherence (rs = 0.21 and 0.16; p = 0.01 and 0.046, respectively). Better knowledge, higher satisfaction, fewer concerns, and better warfarin adherence were associated with good INR control (p = 0.003, 0.02, 0.03 and 0.003, respectively). Conclusions: This study highlighted patients’ concerns and deficits in knowledge regarding warfarin treatment, and also demonstrated their association with warfarin adherence and INR control. © 2014 Elsevier Ltd. All rights reserved.
Introduction Warfarin has been the most commonly used oral anticoagulant to prevent thromboembolism in the past few decades [1]. It increases the international normalized ratio (INR) values to the therapeutic range in patients at risk of thromboembolism [1]. However, the drug’s narrow therapeutic range and considerable variability in inter-individual responses may lead to the occurrences of out-of-range INRs [1]. Studies have shown that subtherapeutic and supratherapeutic INR values are associated with a higher risk of thromboembolism and hemorrhage, respectively [2–4]. Therefore, it is important to adhere to warfarin treatment as prescribed and keep INRs within the therapeutic range. A number of factors may affect INR control in patients taking warfarin. Some factors are inherent, such as genetic variants that can lead to variability in inter-individual warfarin doses and difficulty achieving better INR control [5]. However, other factors that facilitate good INR control are acquired and can be controlled via patients’ behavior. For ⁎ Corresponding author at: Block S4, 18 Science Drive 4, Singapore 117543. Tel.: +65 6516 4182; fax: +65 6779 1554. E-mail addresses: [email protected], [email protected] (Y. Ko). 0049-3848/$ – see front matter © 2014 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.thromres.2014.01.002
example, studies have shown that patients with better knowledge and higher medication adherence to warfarin therapy are more likely to have good INR control [6,7]. As such, it is important to assess and identify the deficits in patients’ knowledge as well as their satisfaction with and concerns of warfarin therapy, all of which may lead to poor warfarin adherence and INR control. With a better understanding of the gaps and needs, targeted interventions can be developed and incorporated into patient education and clinical practice. The aims of this study were two-fold: 1) to identify deficits in patients’ knowledge as well as their satisfaction with and concerns of warfarin therapy, and 2) to assess these results’ association with warfarin adherence and INR control in a multi-ethnic Asian population. Methods Patient Recruitment and Data Collection A cross-sectional survey was conducted in a convenience sample of patients taking warfarin in an anticoagulation clinic (ACC) of the Singapore General Hospital from November, 2012, to April, 2013. The target sample size was 180 in order to have a power of 0.8 to detect a
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small correlation (r = 0.25) between patients’ knowledge of warfarin therapy and INR control at the 5% significance level, assuming 30% incomplete responses. To be eligible, participants had to be age 21 or older, taking warfarin and able to comprehend English or Chinese. Participants who consented to participate were interviewed face-to-face in English or Chinese, depending on their language preference. Prior to survey administration, two interviewers were trained in order to standardize the administration process. The study was approved by the Singhealth Institution Review Board. Patients’ warfarin refill records for the past three months prior to survey administration were retrieved from the hospital electronic databases in order to calculate the warfarin refill adherence, which was equal to the total days of supply divided by the number of evaluated days during the observation period, multiplied by 100 [8]. In addition, patients’ time in the therapeutic INR range (TTR) in the past three months were also retrieved from the same databases. Patients with a TTR of 90% or higher were classified as having good INR control.
Chi-Square test and independent-samples t-test were used where appropriate to compare socio-demographic and clinical characteristics between respondents and non-respondents. Independent-samples t-test and Mann Whitney U test were used where appropriate to compare the difference in knowledge, satisfaction, and concern scores between patients with and those without good INR control. Correlations between knowledge and satisfaction scores were examined using Pearson’s correlation analysis. Spearman’s correlation analysis was used to examine 1) the correlations of concern scores with knowledge and satisfaction scores, and 2) the correlations of warfarin refill adherence with knowledge, satisfaction and concern scores. All analyses were performed using SPSS version 21.0. The level of significance was set at probability (p) b 0.05.
Survey Questionnaire
Among the 258 patients approached, 183 agreed to participate in the survey, giving a response rate of 70.9%. Patients’ characteristics are shown in Table 1. Respondents were evenly distributed between the two genders (49.2% male) and the two language versions (54.6% English) and had a mean ± SD age of 56.1 ± 13.0 years and mean ± SD warfarin refill adherence of 92.0 ± 16.8%. A majority of respondents had TTR of less than 90% (61.2%). Non-respondents were older (p = 0.002) and more likely to speak Chinese (p = 0.02).
The survey questionnaire was developed based on literature review [7,9–31], patient educational materials provided by the ACC and expert opinions. The questionnaire was composed of four parts, including patients’ socio-demographic and warfarin-related clinical characteristics (e.g., duration of taking warfarin), knowledge of warfarin treatment, satisfaction with services and warfarin treatment provided by the ACC, and concerns of warfarin therapy. The two language versions of the questionnaire were evaluated by a panel of multi-disciplinary and bilingual clinical experts (i.e., a researcher with a Ph.D. degree in pharmacy, two physicians with master’s degrees in medicine, a clinical pharmacist with a master’s degree in pharmacy and a Ph.D. candidate in pharmacy) to ensure local adaptation and equivalence in terms of content, wording and cognitive levels. Both language versions were pilot-tested in a group of patients (n = 16) prior to the survey to ensure the questions’ clarity and readability. The knowledge questions consisted of four domains, including warfarin administration (e.g., color of warfarin tablets), warfarin-drug interactions (e.g., interaction between warfarin and aspirin), warfarindiet interactions (e.g., interaction between warfarin and soybean products) and adverse effects (e.g., symptoms of warfarin-induced hemorrhage). Each domain consisted of two to four questions, giving a total of eleven questions. Each question had five options, only one of which was correct. A score of “1” was assigned to each correctly chosen option, giving a total knowledge score that ranged from 0 to 11, with a higher score indicating better knowledge. The satisfaction scale included seven positive statements about the services and warfarin treatment provided by the ACC with Likert-type responses, and each response was assigned a score based on level of satisfaction (i.e., “strongly agree” = 4, “agree” = 3, “neutral” = 2, “disagree” = 1 and “strongly disagree” = 0). Therefore, the total scores of the seven statements ranged from 0 to 28, with a higher score indicating a higher level of satisfaction. The questionnaire also assessed patient-perceived concerns of warfarin therapy. Ten potential concerns were listed, including warfarindrug interactions, forgetting to take warfarin, side effects of warfarin, frequency of hospital visits, warfarin-diet interactions, restrictions on usual activities, impact on work, not believing that warfarin is helpful and difficulty following warfarin instructions. Each concern was given a score of “1”. Patients were asked to tick all concerns they experienced. The total score ranged from 0 to 10, with a higher score indicating more concerns.
Results Patient Characteristics
Survey Outcomes The mean ± SD knowledge score was 6.6 ± 2.3. More elderly patients (r = − 0.47, p b 0.001) and those with lower education (p b 0.001) were more likely to have poor knowledge regarding warfarin treatment. A number of patients (16.9%) gave wrong answers to Table 1 Socio-demographic and Clinical Characteristics. Characteristics
Respondents (n = 183)
Non-respondents (n = 75)
P value
n (%)a Gender Male Female Ethnicity Chinese Malay Indian Others Language English Chinese Educational level No school or primary Secondary Post-secondary Marital status Married Not married Indication for warfarin AF DVT Others TTR in the past 3 months b90 (%) ≥90 (%)
0.68 90 (49.2) 93 (50.8)
39 (52.0) 36 (48.0)
128 (69.9) 32 (17.5) 13 (7.1) 10 (5.5)
58 (77.3) 9 (12.0) 6 (8.0) 2 (2.7)
100 (54.6) 83 (45.4)
29 (38.7) 46 (61.3)
61 (33.3) 66 (36.1) 55 (30.1)
NA NA NA
129 (70.5) 54 (29.5)
NA NA
22 (12.0) 94 (51.4) 64 (35.0)
16 (21.3) 32 (42.7) 26 (34.7)
112 (61.2) 68 (37.2)
54 (72.0) 20 (26.7)
0.50
0.02
NA
NA
0.14
0.10
mean ± SD
Statistical Analysis Descriptive statistics were used to describe patients’ characteristics along with their knowledge, satisfaction and concern scores. Pearson’s
Age (years) Duration for taking warfarin (years)
56.1 ± 13.0 7.4 ± 7.5
61.7 ± 12.8 NA
0.002 NA
AF = atrial fibrillation, DVT = deep vein thrombosis, NA = not available, TTR = time in the therapeutic range. a Percentage may not add up to 100% due to missing values.
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Table 2 Questions on Patients’ Knowledge of Warfarin Therapy (n = 183). Item Warfarin’s adverse effects Symptoms of bleeding Frequency of monitoring signs of bleeding Association between warfarin dosage, INR control and subsequent clinical complication Impact of warfarin on intramuscular injections Warfarin administration Color and number of daily warfarin tablets prescribed Actions to take if a warfarin dose is missed Target INR range Warfarin-drug interactions Consulting doctors when starting a new medicine Medicines that interact with warfarin Warfarin-diet interactions Importance of keeping a consistent diet Food that interacts with warfarin
Correct responses, n (%) 134 (73.2) 100 (54.6) 92 (50.3) 60 (32.8) 144 (78.7) 122 (66.7) 111 (60.7) 150 (82.0) 84 (45.9) 126 (68.9) 86 (47.0)
INR = international normalized ratio.
both questions in the domain of warfarin-diet interactions, and others incorrectly answered questions about warfarin-drug interactions (10.9%), warfarin adverse effects (10.4%) and warfarin administration (3.8%). The percentage of correct answers given to each question is shown in Table 2. The satisfaction scale had a mean ± SD score of 21.2 ± 3.6. Responses to each statement are listed in Table 3. A number of patients (43.2%) were neutral about or unsatisfied with the waiting time to see an ACC pharmacist. The concern scores had a median of 1 and were skewed to the high end. Patients who were new to warfarin were more likely to have more concerns (rs = −0.21, p = 0.004). Approximately one-third (31.7%) of the respondents indicated no concerns. The percentages of patients reporting various concerns regarding warfarin therapy are shown in Table 4. It was found that higher satisfaction scores were associated with both higher knowledge scores (r = 0.24, p = 0.001) and lower concern scores (rs = −0.23, p = 0.002). Moreover, patients with better knowledge and higher satisfaction were more likely to have higher warfarin refill adherence (rs = 0.21 and 0.16; p = 0.01 and 0.046, respectively). Finally, patients with better knowledge, higher satisfaction, fewer concerns, and better warfarin adherence were more likely to have good INR control (p = 0.003, 0.02, 0.03 and 0.003, respectively).
Discussion In this study, on average, patients had a moderate level of warfarin knowledge. This finding was consistent with a few previous studies that found poor to moderate levels of warfarin knowledge in patients taking warfarin [7,32,33]. However, a closer look at patients’ responses
revealed that there were some consistent knowledge deficits in most respondents. In particular, similar to the findings of previous studies [18,34], patients had inadequate knowledge of warfarin-diet interactions and warfarin-drug interactions. Studies have shown that changes in dietary intake of vitamin K can impact the effect of warfarin and lead to unstable INR control [35,36]. In addition, it is known that patients taking warfarin are susceptible to a number of drug interactions, which may lead to severe bleeding [37]. Therefore, the findings of this study demonstrated that future patient educational programs should focus on warfarin-diet and warfarin-drug interactions. Consistent with previous studies [7,38], it was found that more elderly patients and patients with lower education were more likely to have poor knowledge of warfarin treatment. This could be due to the fact that these patients had more difficulty comprehending educational materials (e.g., the educational booklet provided by the ACC) and communicating with healthcare providers. In a busy ACC, patients are often assumed to be able to comprehend written educational materials and oral communication about their warfarin treatment, and the problem of inadequate health literacy in older and poorly educated patients may be overlooked. The lack of knowledge about warfarin treatment in elderly patients can severely affect patients’ INR control because they often take several medications simultaneously for multiple chronic conditions, which subjects them to a high risk of warfarin-drug interactions [37]. Therefore, education in these patients may require special consideration. Innovative and patient-targeted educational programs (e.g., video-assisted programs) and improvement in pharmacist-patient communication are needed [39,40]. In this study, patients had a moderate level of satisfaction with services and warfarin treatment provided by the ACC. The largest complaint was about the long waiting time to visit an ACC pharmacist, which could be due to the large number of daily appointments and limited healthcare resources in the busy ACC. The number of pharmacists needs to be increased to reduce the waiting time, which may also increase the time for pharmacist-patient communication. A number of respondents reported worries about warfarin-drug interactions, the side effects of warfarin, and warfarin-diet interactions. These concerns could be overcome by improving relevant knowledge of warfarin treatment via patient education, particularly for those who have newly started warfarin treatment. Moreover, interventions such as pill boxes can be used to help patients who forget to take warfarin to improve their adherence to warfarin therapy. For patients who found that it was difficult to take warfarin due to frequent hospital visits, home INR testing may be implemented based on structured patient training [14]. A few studies have supported self-management of INR control because it incorporates more frequent INR tests, higher levels of medical safety and less frequent hospital visits [41,42]. One approach to keeping INRs within the therapeutic range is to control the risk factors of out-of-range INRs, which can be either genetic or environmental. Genetic factors (e.g., variants of Cytochrome P450 2C9 and vitamin K epoxide reductase complex subunit 1) can lead to variability in inter-individual responses to warfarin doses and thus require individualized dosing strategies [43,44]. These factors are inherent
Table 3 Distribution of Responses to Each Statement in the Satisfaction Scale (n = 183). Statements
Strongly agree
Agree
Neutral
Disagree
Strongly disagree
59 (32.2) 49 (26.8) 60 (32.8) 40 (21.9) 40 (21.9) 41 (22.4)
112 (61.2) 112 (61.2) 111 (60.7) 124 (67.8) 113 (61.7) 105 (57.4)
9 (4.9) 15 (8.2) 11 (6.0) 14 (7.7) 25 (13.7) 28 (15.3)
2 (1.1) 6 (3.3) 1 (0.5) 5 (2.7) 5 (2.7) 9 (4.9)
1 (0.5) 1 (0.5) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0)
23 (12.6)
81 (44.3)
53 (29.0)
21 (11.5)
5 (2.7)
n (%) 1. The ACC pharmacists can give you useful, clear and sufficient instructions on your warfarin treatment. 2. You have been given enough time to discuss with the ACC pharmacists during your visits. 3. The ACC pharmacists are friendly and caring. 4. Since you began your treatment at the ACC, you have felt reassured about your warfarin treatment. 5. Since you began your treatment at the ACC, your blood thickness (INR results) has been better controlled. 6. You are satisfied with the frequency of your ACC appointments at Singapore General Hospital for your warfarin treatment. 7. You are satisfied with your waiting time in the ACC to see the pharmacist. ACC = anticoagulation clinic, INR = international normalized ratio.
Y. Wang et al. / Thrombosis Research 133 (2014) 550–554 Table 4 Concerns Regarding Warfarin Therapy (n = 183). Concern
n (%)
1. Warfarin-drug interactions 2. Forgetting to take warfarin 3. Side effects of warfarin 4. High frequency of hospital visits 5. Warfarin-diet interactions 6. Restrictions on usual activities 7. Impact on work 8. Not believing that warfarin is helpful 9. Difficulty following warfarin instructions 10. Others
66 (36.1) 48 (26.2) 47 (25.7) 44 (24.0) 41 (22.4) 16 (8.7) 16 (8.7) 7 (3.8) 6 (3.3) 2 (1.1)
and cannot be controlled by patients’ behavior. In contrast, environmental factors (e.g., dietary intake of vitamin K) are acquired and can be managed by patients in order to improve their INR control. In this study, it was found that patients with better knowledge, higher satisfaction and fewer concerns regarding warfarin therapy were more likely to have good INR control, indicating the significant effects of these factors on INR control and the importance of controlling them. There are several limitations to this study. First, respondents in this study were recruited from an outpatient ACC; therefore, the findings may not be generalizable to patients with poorer INR control in the inpatient setting. Second, selection bias may have existed due to the convenience sampling procedure. Patients with poorer knowledge and lower satisfaction may have had poorer medication adherence and may have been less likely to visit healthcare providers or more likely to have passed away as a consequence of non-adherence. Third, the questionnaire used in this study was in its early stages of development. Its psychometric properties need to be further assessed in future studies. In conclusion, the findings of this study highlighted the deficits in patients’ knowledge and satisfaction regarding warfarin therapy and concerns of taking warfarin and identified the areas for improvement in patient education. In addition, this study demonstrated the association of patients’ knowledge, satisfaction and concerns regarding warfarin treatment with warfarin adherence and INR control, indicating that the negative impact of these deficits on the effect of warfarin therapy could be important and severe. Therefore, patient-targeted and structured educational programs as well as efficient pharmacist-patient communication are needed to make warfarin treatment more successful. Conflict of Interest Statement The authors have no conflicts of interest to declare. Acknowledgements This study was sponsored by Dr Ko's start-up research grant provided by the National University of Singapore. References [1] Ansell J, Hirsh J, Poller L, Bussey H, Jacobson A, Hylek E. The pharmacology and management of the vitamin K antagonists: the seventh ACCP conference on antithrombotic and thrombolytic therapy. Chest 2004;126:204S–33S. [2] Hylek EM, Go AS, Chang Y, Jensvold NG, Henault LE, Selby JV, et al. Effect of intensity of oral anticoagulation on stroke severity and mortality in atrial fibrillation. N Engl J Med 2003;349:1019–26. [3] Levine MN, Raskob G, Beyth RJ, Kearon C, Schulman S. Hemorrhagic complications of anticoagulant treatment: the seventh ACCP conference on antithrombotic and thrombolytic therapy. Chest 2004;126:287S–310S. [4] Merli GJ, Tzanis G. Warfarin: what are the clinical implications of an out-of-rangetherapeutic international normalized ratio? J Thromb Thrombolysis 2009;27:293–9. [5] Krynetskiy E, McDonnell P. Building individualized medicine: prevention of adverse reactions to warfarin therapy. J Pharmacol Exp Ther 2007;322:427–34. [6] Wang Y, Kong MC, Ko Y. Comparison of three medication adherence measures in patients taking warfarin. J Thromb Thrombolysis 2013;36:416–21.
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Contents lists available at ScienceDirect
Thrombosis Research journal homepage: www.elsevier.com/locate/thromres
Regular Article
Knowledge, satisfaction, and concerns regarding warfarin therapy and their association with warfarin adherence and anticoagulation control Ye Wang a, Ming Chai Kong b, Lai Heng Lee c, Heng Joo Ng c, Yu Ko a,⁎ a b c
Department of Pharmacy, Faculty of Science, National University of Singapore, Singapore Department of Pharmacy, Singapore General Hospital, Singapore Department of Haematology, Singapore General Hospital, Singapore
a r t i c l e
i n f o
Article history: Received 8 October 2013 Received in revised form 20 December 2013 Accepted 3 January 2014 Available online 7 January 2014 Keywords: Anticoagulant Concerns Knowledge Medication adherence Satisfaction Warfarin
a b s t r a c t Introduction: A better understanding of patients’ knowledge, satisfaction and concerns can identify deficits and help develop targeted patient education. This study aimed to examine patients’ knowledge, satisfaction and concerns regarding warfarin therapy and assess their association with warfarin adherence and international normalized ratio (INR) control. Materials and methods: A cross-sectional survey was conducted in a convenience sample of patients taking warfarin in an anticoagulation clinic. The questionnaire consisted of questions on patients’ knowledge, satisfaction and concerns regarding warfarin treatment. Patients’ warfarin refill records and time within the therapeutic INR range were retrieved from hospital databases. Results: One hundred and eighty-three patients participated in the survey. Patients had inadequate knowledge of warfarin-diet and warfarin-drug interactions. Over 40% of the respondents were not satisfied with the waiting time to see a pharmacist. The most common concerns of taking warfarin were worries about warfarin-drug interactions (36.1%), forgetting to take warfarin (26.2%) and worries about side effects (25.7%). Higher satisfaction was associated with better knowledge (r = 0.24, p = 0.001) and fewer concerns (rs = − 0.23, p = 0.002). Better knowledge and higher satisfaction were associated with higher warfarin adherence (rs = 0.21 and 0.16; p = 0.01 and 0.046, respectively). Better knowledge, higher satisfaction, fewer concerns, and better warfarin adherence were associated with good INR control (p = 0.003, 0.02, 0.03 and 0.003, respectively). Conclusions: This study highlighted patients’ concerns and deficits in knowledge regarding warfarin treatment, and also demonstrated their association with warfarin adherence and INR control. © 2014 Elsevier Ltd. All rights reserved.
Introduction Warfarin has been the most commonly used oral anticoagulant to prevent thromboembolism in the past few decades [1]. It increases the international normalized ratio (INR) values to the therapeutic range in patients at risk of thromboembolism [1]. However, the drug’s narrow therapeutic range and considerable variability in inter-individual responses may lead to the occurrences of out-of-range INRs [1]. Studies have shown that subtherapeutic and supratherapeutic INR values are associated with a higher risk of thromboembolism and hemorrhage, respectively [2–4]. Therefore, it is important to adhere to warfarin treatment as prescribed and keep INRs within the therapeutic range. A number of factors may affect INR control in patients taking warfarin. Some factors are inherent, such as genetic variants that can lead to variability in inter-individual warfarin doses and difficulty achieving better INR control [5]. However, other factors that facilitate good INR control are acquired and can be controlled via patients’ behavior. For ⁎ Corresponding author at: Block S4, 18 Science Drive 4, Singapore 117543. Tel.: +65 6516 4182; fax: +65 6779 1554. E-mail addresses: [email protected], [email protected] (Y. Ko). 0049-3848/$ – see front matter © 2014 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.thromres.2014.01.002
example, studies have shown that patients with better knowledge and higher medication adherence to warfarin therapy are more likely to have good INR control [6,7]. As such, it is important to assess and identify the deficits in patients’ knowledge as well as their satisfaction with and concerns of warfarin therapy, all of which may lead to poor warfarin adherence and INR control. With a better understanding of the gaps and needs, targeted interventions can be developed and incorporated into patient education and clinical practice. The aims of this study were two-fold: 1) to identify deficits in patients’ knowledge as well as their satisfaction with and concerns of warfarin therapy, and 2) to assess these results’ association with warfarin adherence and INR control in a multi-ethnic Asian population. Methods Patient Recruitment and Data Collection A cross-sectional survey was conducted in a convenience sample of patients taking warfarin in an anticoagulation clinic (ACC) of the Singapore General Hospital from November, 2012, to April, 2013. The target sample size was 180 in order to have a power of 0.8 to detect a
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small correlation (r = 0.25) between patients’ knowledge of warfarin therapy and INR control at the 5% significance level, assuming 30% incomplete responses. To be eligible, participants had to be age 21 or older, taking warfarin and able to comprehend English or Chinese. Participants who consented to participate were interviewed face-to-face in English or Chinese, depending on their language preference. Prior to survey administration, two interviewers were trained in order to standardize the administration process. The study was approved by the Singhealth Institution Review Board. Patients’ warfarin refill records for the past three months prior to survey administration were retrieved from the hospital electronic databases in order to calculate the warfarin refill adherence, which was equal to the total days of supply divided by the number of evaluated days during the observation period, multiplied by 100 [8]. In addition, patients’ time in the therapeutic INR range (TTR) in the past three months were also retrieved from the same databases. Patients with a TTR of 90% or higher were classified as having good INR control.
Chi-Square test and independent-samples t-test were used where appropriate to compare socio-demographic and clinical characteristics between respondents and non-respondents. Independent-samples t-test and Mann Whitney U test were used where appropriate to compare the difference in knowledge, satisfaction, and concern scores between patients with and those without good INR control. Correlations between knowledge and satisfaction scores were examined using Pearson’s correlation analysis. Spearman’s correlation analysis was used to examine 1) the correlations of concern scores with knowledge and satisfaction scores, and 2) the correlations of warfarin refill adherence with knowledge, satisfaction and concern scores. All analyses were performed using SPSS version 21.0. The level of significance was set at probability (p) b 0.05.
Survey Questionnaire
Among the 258 patients approached, 183 agreed to participate in the survey, giving a response rate of 70.9%. Patients’ characteristics are shown in Table 1. Respondents were evenly distributed between the two genders (49.2% male) and the two language versions (54.6% English) and had a mean ± SD age of 56.1 ± 13.0 years and mean ± SD warfarin refill adherence of 92.0 ± 16.8%. A majority of respondents had TTR of less than 90% (61.2%). Non-respondents were older (p = 0.002) and more likely to speak Chinese (p = 0.02).
The survey questionnaire was developed based on literature review [7,9–31], patient educational materials provided by the ACC and expert opinions. The questionnaire was composed of four parts, including patients’ socio-demographic and warfarin-related clinical characteristics (e.g., duration of taking warfarin), knowledge of warfarin treatment, satisfaction with services and warfarin treatment provided by the ACC, and concerns of warfarin therapy. The two language versions of the questionnaire were evaluated by a panel of multi-disciplinary and bilingual clinical experts (i.e., a researcher with a Ph.D. degree in pharmacy, two physicians with master’s degrees in medicine, a clinical pharmacist with a master’s degree in pharmacy and a Ph.D. candidate in pharmacy) to ensure local adaptation and equivalence in terms of content, wording and cognitive levels. Both language versions were pilot-tested in a group of patients (n = 16) prior to the survey to ensure the questions’ clarity and readability. The knowledge questions consisted of four domains, including warfarin administration (e.g., color of warfarin tablets), warfarin-drug interactions (e.g., interaction between warfarin and aspirin), warfarindiet interactions (e.g., interaction between warfarin and soybean products) and adverse effects (e.g., symptoms of warfarin-induced hemorrhage). Each domain consisted of two to four questions, giving a total of eleven questions. Each question had five options, only one of which was correct. A score of “1” was assigned to each correctly chosen option, giving a total knowledge score that ranged from 0 to 11, with a higher score indicating better knowledge. The satisfaction scale included seven positive statements about the services and warfarin treatment provided by the ACC with Likert-type responses, and each response was assigned a score based on level of satisfaction (i.e., “strongly agree” = 4, “agree” = 3, “neutral” = 2, “disagree” = 1 and “strongly disagree” = 0). Therefore, the total scores of the seven statements ranged from 0 to 28, with a higher score indicating a higher level of satisfaction. The questionnaire also assessed patient-perceived concerns of warfarin therapy. Ten potential concerns were listed, including warfarindrug interactions, forgetting to take warfarin, side effects of warfarin, frequency of hospital visits, warfarin-diet interactions, restrictions on usual activities, impact on work, not believing that warfarin is helpful and difficulty following warfarin instructions. Each concern was given a score of “1”. Patients were asked to tick all concerns they experienced. The total score ranged from 0 to 10, with a higher score indicating more concerns.
Results Patient Characteristics
Survey Outcomes The mean ± SD knowledge score was 6.6 ± 2.3. More elderly patients (r = − 0.47, p b 0.001) and those with lower education (p b 0.001) were more likely to have poor knowledge regarding warfarin treatment. A number of patients (16.9%) gave wrong answers to Table 1 Socio-demographic and Clinical Characteristics. Characteristics
Respondents (n = 183)
Non-respondents (n = 75)
P value
n (%)a Gender Male Female Ethnicity Chinese Malay Indian Others Language English Chinese Educational level No school or primary Secondary Post-secondary Marital status Married Not married Indication for warfarin AF DVT Others TTR in the past 3 months b90 (%) ≥90 (%)
0.68 90 (49.2) 93 (50.8)
39 (52.0) 36 (48.0)
128 (69.9) 32 (17.5) 13 (7.1) 10 (5.5)
58 (77.3) 9 (12.0) 6 (8.0) 2 (2.7)
100 (54.6) 83 (45.4)
29 (38.7) 46 (61.3)
61 (33.3) 66 (36.1) 55 (30.1)
NA NA NA
129 (70.5) 54 (29.5)
NA NA
22 (12.0) 94 (51.4) 64 (35.0)
16 (21.3) 32 (42.7) 26 (34.7)
112 (61.2) 68 (37.2)
54 (72.0) 20 (26.7)
0.50
0.02
NA
NA
0.14
0.10
mean ± SD
Statistical Analysis Descriptive statistics were used to describe patients’ characteristics along with their knowledge, satisfaction and concern scores. Pearson’s
Age (years) Duration for taking warfarin (years)
56.1 ± 13.0 7.4 ± 7.5
61.7 ± 12.8 NA
0.002 NA
AF = atrial fibrillation, DVT = deep vein thrombosis, NA = not available, TTR = time in the therapeutic range. a Percentage may not add up to 100% due to missing values.
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Table 2 Questions on Patients’ Knowledge of Warfarin Therapy (n = 183). Item Warfarin’s adverse effects Symptoms of bleeding Frequency of monitoring signs of bleeding Association between warfarin dosage, INR control and subsequent clinical complication Impact of warfarin on intramuscular injections Warfarin administration Color and number of daily warfarin tablets prescribed Actions to take if a warfarin dose is missed Target INR range Warfarin-drug interactions Consulting doctors when starting a new medicine Medicines that interact with warfarin Warfarin-diet interactions Importance of keeping a consistent diet Food that interacts with warfarin
Correct responses, n (%) 134 (73.2) 100 (54.6) 92 (50.3) 60 (32.8) 144 (78.7) 122 (66.7) 111 (60.7) 150 (82.0) 84 (45.9) 126 (68.9) 86 (47.0)
INR = international normalized ratio.
both questions in the domain of warfarin-diet interactions, and others incorrectly answered questions about warfarin-drug interactions (10.9%), warfarin adverse effects (10.4%) and warfarin administration (3.8%). The percentage of correct answers given to each question is shown in Table 2. The satisfaction scale had a mean ± SD score of 21.2 ± 3.6. Responses to each statement are listed in Table 3. A number of patients (43.2%) were neutral about or unsatisfied with the waiting time to see an ACC pharmacist. The concern scores had a median of 1 and were skewed to the high end. Patients who were new to warfarin were more likely to have more concerns (rs = −0.21, p = 0.004). Approximately one-third (31.7%) of the respondents indicated no concerns. The percentages of patients reporting various concerns regarding warfarin therapy are shown in Table 4. It was found that higher satisfaction scores were associated with both higher knowledge scores (r = 0.24, p = 0.001) and lower concern scores (rs = −0.23, p = 0.002). Moreover, patients with better knowledge and higher satisfaction were more likely to have higher warfarin refill adherence (rs = 0.21 and 0.16; p = 0.01 and 0.046, respectively). Finally, patients with better knowledge, higher satisfaction, fewer concerns, and better warfarin adherence were more likely to have good INR control (p = 0.003, 0.02, 0.03 and 0.003, respectively).
Discussion In this study, on average, patients had a moderate level of warfarin knowledge. This finding was consistent with a few previous studies that found poor to moderate levels of warfarin knowledge in patients taking warfarin [7,32,33]. However, a closer look at patients’ responses
revealed that there were some consistent knowledge deficits in most respondents. In particular, similar to the findings of previous studies [18,34], patients had inadequate knowledge of warfarin-diet interactions and warfarin-drug interactions. Studies have shown that changes in dietary intake of vitamin K can impact the effect of warfarin and lead to unstable INR control [35,36]. In addition, it is known that patients taking warfarin are susceptible to a number of drug interactions, which may lead to severe bleeding [37]. Therefore, the findings of this study demonstrated that future patient educational programs should focus on warfarin-diet and warfarin-drug interactions. Consistent with previous studies [7,38], it was found that more elderly patients and patients with lower education were more likely to have poor knowledge of warfarin treatment. This could be due to the fact that these patients had more difficulty comprehending educational materials (e.g., the educational booklet provided by the ACC) and communicating with healthcare providers. In a busy ACC, patients are often assumed to be able to comprehend written educational materials and oral communication about their warfarin treatment, and the problem of inadequate health literacy in older and poorly educated patients may be overlooked. The lack of knowledge about warfarin treatment in elderly patients can severely affect patients’ INR control because they often take several medications simultaneously for multiple chronic conditions, which subjects them to a high risk of warfarin-drug interactions [37]. Therefore, education in these patients may require special consideration. Innovative and patient-targeted educational programs (e.g., video-assisted programs) and improvement in pharmacist-patient communication are needed [39,40]. In this study, patients had a moderate level of satisfaction with services and warfarin treatment provided by the ACC. The largest complaint was about the long waiting time to visit an ACC pharmacist, which could be due to the large number of daily appointments and limited healthcare resources in the busy ACC. The number of pharmacists needs to be increased to reduce the waiting time, which may also increase the time for pharmacist-patient communication. A number of respondents reported worries about warfarin-drug interactions, the side effects of warfarin, and warfarin-diet interactions. These concerns could be overcome by improving relevant knowledge of warfarin treatment via patient education, particularly for those who have newly started warfarin treatment. Moreover, interventions such as pill boxes can be used to help patients who forget to take warfarin to improve their adherence to warfarin therapy. For patients who found that it was difficult to take warfarin due to frequent hospital visits, home INR testing may be implemented based on structured patient training [14]. A few studies have supported self-management of INR control because it incorporates more frequent INR tests, higher levels of medical safety and less frequent hospital visits [41,42]. One approach to keeping INRs within the therapeutic range is to control the risk factors of out-of-range INRs, which can be either genetic or environmental. Genetic factors (e.g., variants of Cytochrome P450 2C9 and vitamin K epoxide reductase complex subunit 1) can lead to variability in inter-individual responses to warfarin doses and thus require individualized dosing strategies [43,44]. These factors are inherent
Table 3 Distribution of Responses to Each Statement in the Satisfaction Scale (n = 183). Statements
Strongly agree
Agree
Neutral
Disagree
Strongly disagree
59 (32.2) 49 (26.8) 60 (32.8) 40 (21.9) 40 (21.9) 41 (22.4)
112 (61.2) 112 (61.2) 111 (60.7) 124 (67.8) 113 (61.7) 105 (57.4)
9 (4.9) 15 (8.2) 11 (6.0) 14 (7.7) 25 (13.7) 28 (15.3)
2 (1.1) 6 (3.3) 1 (0.5) 5 (2.7) 5 (2.7) 9 (4.9)
1 (0.5) 1 (0.5) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0)
23 (12.6)
81 (44.3)
53 (29.0)
21 (11.5)
5 (2.7)
n (%) 1. The ACC pharmacists can give you useful, clear and sufficient instructions on your warfarin treatment. 2. You have been given enough time to discuss with the ACC pharmacists during your visits. 3. The ACC pharmacists are friendly and caring. 4. Since you began your treatment at the ACC, you have felt reassured about your warfarin treatment. 5. Since you began your treatment at the ACC, your blood thickness (INR results) has been better controlled. 6. You are satisfied with the frequency of your ACC appointments at Singapore General Hospital for your warfarin treatment. 7. You are satisfied with your waiting time in the ACC to see the pharmacist. ACC = anticoagulation clinic, INR = international normalized ratio.
Y. Wang et al. / Thrombosis Research 133 (2014) 550–554 Table 4 Concerns Regarding Warfarin Therapy (n = 183). Concern
n (%)
1. Warfarin-drug interactions 2. Forgetting to take warfarin 3. Side effects of warfarin 4. High frequency of hospital visits 5. Warfarin-diet interactions 6. Restrictions on usual activities 7. Impact on work 8. Not believing that warfarin is helpful 9. Difficulty following warfarin instructions 10. Others
66 (36.1) 48 (26.2) 47 (25.7) 44 (24.0) 41 (22.4) 16 (8.7) 16 (8.7) 7 (3.8) 6 (3.3) 2 (1.1)
and cannot be controlled by patients’ behavior. In contrast, environmental factors (e.g., dietary intake of vitamin K) are acquired and can be managed by patients in order to improve their INR control. In this study, it was found that patients with better knowledge, higher satisfaction and fewer concerns regarding warfarin therapy were more likely to have good INR control, indicating the significant effects of these factors on INR control and the importance of controlling them. There are several limitations to this study. First, respondents in this study were recruited from an outpatient ACC; therefore, the findings may not be generalizable to patients with poorer INR control in the inpatient setting. Second, selection bias may have existed due to the convenience sampling procedure. Patients with poorer knowledge and lower satisfaction may have had poorer medication adherence and may have been less likely to visit healthcare providers or more likely to have passed away as a consequence of non-adherence. Third, the questionnaire used in this study was in its early stages of development. Its psychometric properties need to be further assessed in future studies. In conclusion, the findings of this study highlighted the deficits in patients’ knowledge and satisfaction regarding warfarin therapy and concerns of taking warfarin and identified the areas for improvement in patient education. In addition, this study demonstrated the association of patients’ knowledge, satisfaction and concerns regarding warfarin treatment with warfarin adherence and INR control, indicating that the negative impact of these deficits on the effect of warfarin therapy could be important and severe. Therefore, patient-targeted and structured educational programs as well as efficient pharmacist-patient communication are needed to make warfarin treatment more successful. Conflict of Interest Statement The authors have no conflicts of interest to declare. Acknowledgements This study was sponsored by Dr Ko's start-up research grant provided by the National University of Singapore. References [1] Ansell J, Hirsh J, Poller L, Bussey H, Jacobson A, Hylek E. The pharmacology and management of the vitamin K antagonists: the seventh ACCP conference on antithrombotic and thrombolytic therapy. Chest 2004;126:204S–33S. [2] Hylek EM, Go AS, Chang Y, Jensvold NG, Henault LE, Selby JV, et al. Effect of intensity of oral anticoagulation on stroke severity and mortality in atrial fibrillation. N Engl J Med 2003;349:1019–26. [3] Levine MN, Raskob G, Beyth RJ, Kearon C, Schulman S. Hemorrhagic complications of anticoagulant treatment: the seventh ACCP conference on antithrombotic and thrombolytic therapy. Chest 2004;126:287S–310S. [4] Merli GJ, Tzanis G. Warfarin: what are the clinical implications of an out-of-rangetherapeutic international normalized ratio? J Thromb Thrombolysis 2009;27:293–9. [5] Krynetskiy E, McDonnell P. Building individualized medicine: prevention of adverse reactions to warfarin therapy. J Pharmacol Exp Ther 2007;322:427–34. [6] Wang Y, Kong MC, Ko Y. Comparison of three medication adherence measures in patients taking warfarin. J Thromb Thrombolysis 2013;36:416–21.
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