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Atrial fibrillation patients’ experiences and perspectives of anticoagulation therapy changes
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Atrial fibrillation patients’ experiences and perspectives of anticoagulation therapy changes Shahrzad Salmasia,b, Anita I. Kapanena,b, Leanne Kwanc, Jason G. Andraded,e, Mary A. De Veraa,b, Peter Loewena,b,∗ a
Collaboration for Outcomes Research and Evaluation (CORE), University of British Columbia, Vancouver, Canada Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, Canada c Atrial Fibrillation Clinic, Royal Columbian Hospital, New Westminster, Canada d Atrial Fibrillation Clinic, Vancouver General Hospital, Vancouver, Canada e Department of Medicine, Faculty of Medicine, University of British Columbia, Vancouver, Canada b
ABSTRACT
Background: Atrial fibrillation (AF) patients’ experiences with changes in their oral anticoagulant (OAC) therapy are understudied. Objective: The objective of this study was to qualitatively describe AF patients’ experiences and perspectives of changes made to their OAC therapy (switches or discontinuations). Methods: A thematic analysis was performed on systematically-collected qualitative data from AF patients who experienced a therapy change (switching or discontinuing an OAC) as part of their participation in a large 2-year prospective observational study. Results: A total of 56 participants met the inclusion criteria. Six themes emerged from the data: 1. reasons for switch or discontinuation of therapy, 2. attitudes towards changes in therapy attributes, 3. challenges with taking medications after therapy change, 4. relief from perceived burden of medication after discontinuation, 5. patients’ limited involvement in decision-making, and 6. inadequate education and follow up. Patients were found to request changes in therapy based on their subjective experience with it (rather than clinically justified reasons). They were found to have limited knowledge about their medications, differing reactions to changes in their therapy attributes after a switch, an overall negative attitude towards taking medications, adherence challenges after switching from once daily to twice daily medication, feelings of being excluded from the decision-making process about their therapy changes and feelings of being unsupported after these changes. Conclusions: There are clear opportunities to improve patients’ experiences with OAC therapy changes through improved shared decision-making and patient education/counselling.
Background Atrial fibrillation (AF) is the most common clinically significant arrhythmia, and a very potent risk factor for stroke.1–5 Oral anticoagulants (OACs), including warfarin and non-vitamin K oral anticoagulants (NOACs: apixaban, dabigatran, edoxaban, and rivaroxaban) are very effective for stroke prevention in AF patients.1,6–10 OAC prescribing in AF is influenced by a complex matrix of patient and prescriber factors, reimbursement policies, and medication attributes including efficacy, bleeding risk, dosing regimen, monitoring requirements, cost, and antidote availability. Patients also have personal values and preferences related to AF stroke prevention which they are not always able to clarify and effectively communicate to the prescriber.11–26 The process to find the most appropriate OAC for a particular patient, therefore, often involves a trial and error period including switches between OACs. Limited evidence suggests that over 30% of AF
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patients experience a switch in therapy.27 It is also not uncommon for patients to experience temporary or permanent discontinuation (e.g. following serious bleeding or stroke risk reassessment or due to surgical procedures, or acute conditions that increase risk of bleeding) of their OACs.28–35 Established psychological and behavioral-change theories (e.g. the health belief model, the common-sense model) have linked patients' perception, beliefs and experiences with therapy to their behaviors such as medication adherence.36,37 These common therapy changes have not been studied from patients' perspective. Patients' experiences, beliefs, and perceptions have been shown to be directly associated with therapy satisfaction and adherence.15,38–40 The objective of this exploratory study was to qualitatively describe AF patients’ subjective experiences with changes made to their OAC therapy.
Corresponding author. Faculty of Pharmaceutical Sciences, The University of British Columbia, 2405 Wesbrook Mall, Vancouver, BC, V6T 1Z3, Canada. E-mail address: [email protected] (P. Loewen).
https://doi.org/10.1016/j.sapharm.2020.01.004 Received 18 September 2019; Received in revised form 2 January 2020; Accepted 12 January 2020 1551-7411/ © 2020 Published by Elsevier Inc.
Please cite this article as: Shahrzad Salmasi, et al., Research in Social and Administrative Pharmacy, https://doi.org/10.1016/j.sapharm.2020.01.004
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Methods
Data analysis
A multicenter, prospective, longitudinal cohort study was conducted at British Columbia's (UBC) five specialized AF clinics. The qualitative data collected from a subgroup of participants in that study who experienced a change (switch or discontinuation) in their OAC therapy was retrospectively analyzed. Ethical approval was granted by the research ethics boards of the University of British Columbia, Interior Health, Fraser Health, Vancouver Island Health, Providence Health, and Vancouver Coastal Health.41
For every participant, a summary of their clinical case was prepared which involved their index OAC, current OAC, reason for switch, records of discontinuations with reason to provide the context in which their responses were interpreted. The data were analyzed using inductive qualitative thematic analysis following the steps recommended by Braun and colleagues.42 Analysis involved 1.data immersion: reading the responses several times; 2.code generation: line by line freecoding with as many codes as needed and 3. theme generation: assessing the homogeneity and heterogeneity between the codes to group them under categories and identify themes; and 4. reviewing themes to ensure coherence of data within themes, and clear and identifiable distinctions between themes.42 Data were coded by one researcher; however coding was frequently discussed with and reviewed by the senior author. The reporting of this study follows the COREQ recommendations (checklist attached).
Study design The longitudinal study enrolled 388 AF patients prescribed OACs. Participants were followed prospectively with quarterly telephone interviews for 2 years, or until patients dropped out, permanently discontinued OAC therapy, or died, whichever came first. Every phone interview was referred to as a “study visit” and conducted without the presence of nonparticipants. The interviewers were undergraduate and graduate pharmacy students or the study coordinator (PhD) who were not involved in the care of the patient. The interview questions were developed by the study team based on their clinical and research experience with AF patients. All interviewers were trained by the study coordinator (AK), observed for their first interview, and given feedback before conducting interviews independently. At every study visit the following open-ended questions were asked: 1) Have your feelings about your medication changed since we last talked?; 2) What kinds of things, if any, make it difficult to take your [name of OAC] as prescribed?; 3) Why do you think it is important to take your medication as prescribed?; 4) Are you happy with the number of daily doses, or would you have preferred something else?; and 5) What, if anything, could help you take your [name of OAC] more consistently? In every visit, patients were also asked if the name or dose of their OAC had changed since the previous visit. If a patient reported having switched medications or discontinued therapy, they were asked the following additional openended questions to capture their experiences about the change: Tell me the whole story on why or how the therapy was switched or stopped; and so far, how is it going for you since the change? Participants were also invited to share any additional thoughts they had at the end of each study visit. Detailed notes, including quotations, wherever possible, were taken by the interviewer during the interview. The data were entered into the study electronic database within half an hour of the completion of the interview. The responses were not processed or analyzed until the completion of the study.
Results Of the 388 patients recruited, 56 experienced a switch or discontinuation of therapy, over a mean follow-up of 14.5 (SD = 6.0) months, forming the target sample of this qualitative study (Table 1). The majority were male (71.4%), married (71%), and Caucasian (88%) with mean age of 66.6 years (SD = 9.6). The study population represented 33 switches between OACs (6 switches between NOACs, 11 from NOAC to warfarin, and 16 from warfarin to NOAC) and 25 therapy discontinuations. Data from 171 interviews across the 56 included patients were used in the qualitative analysis, leading to emergence of six themes: 1. Reasons for switch or discontinuation of therapy, 2. Attitudes towards changes in therapy attributes, 3. Challenges with medication taking after therapy change, 4. Relief from perceived burden of medication after discontinuation, 5. Patients’ limited involvement in Table 1 Characteristic of the included participants.
Participants This qualitative study focused on participants who underwent a change in anticoagulant therapy (switch or discontinuation). Therapy changes could be patient- or clinician-initiated. Switches were defined as changing from one OAC to another. Therapy discontinuation was defined as temporary or permanent discontinuation of OAC therapy, including switching to antiplatelet therapy. Data processing Demographic and clinical information and answers to open-ended questions were extracted from the online survey tool for participants who, at any point during the study, experienced a switch or discontinuation of their OAC therapy. Interview data were extracted for all study visits of the eligible participant (from cohort entry until end of follow up); not just the study visit in which therapy change was identified. Data were exported to Nvivo software® (QSR International Pty Ltd. Version 12) for analysis.
Characteristics
N (%) unless otherwise stated
CHA2DS2-VASca, Mean (SD) HASBLEDb, Mean (SD) Age, Mean (SD) AF type Paroxysmal Persistent Long term persistent Permanent Unknown Sex (Male) Highest education level achieved Elementary High school or equivalent Vocational/technical school Some college/university Undergraduate college/university degree Graduate or professional degree Race Other Caucasian/White Marital status Single/Never married Common-law/married
2.5 (1.6) 1.4 (0.9) 66.6 (9.6) 35 (62.5) 8 (14.3) 5 (8.9) 5 (8.9) 3 (5.4) 40 (71.4) 2 (3.6) 10 (17.9) 4 (7.1) 18 (32.1) 12 (21.4) 10 (17.9) 7 (12.5) 49 (87.5) 16 (28.6) 40 (71.4)
a CHA2DS2-VASc: stroke risk score calculated based on presence of comorbidities. Cardiomyopathy (1 score), Hypertension (1 score), Age≥75(2 scores), Diabetes (1 score), Stroke (2 scores), Vascular disease (1 score), Age 65–75 (1 score), Sex category female(1 score). b HASBLED: bleeding risk score calculated based on presence of comorbidities: Hypertension (1 score), Abnormal liver/kidney function (1 score), Stroke (1 score), Bleeding(1 score), Labile INR(1 score), Elderly > 75 years(1 score), Drugs or alcohol use(1 score).
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Table 2 Representative patient quotes. Theme Theme 1: Reasons for switching/stopping
Representative quote
“I had back pain in May and I thought it might have been due to Xarelto.[…]. They said it was due to arthritis pain in my neck, not because of the medication.” “I couldn't stand the itch and rash, so I stopped three weeks ago to take it [OAC], skin reaction reduced but I took one pill two days ago and now I'm on really bad itch again, so this blood thinner is not doing any good for me.” “I thought I had a rash and swelling in my feet from it when I was in Greece however it was determined not to be caused by warfarin” “Yes, now I'm off of it for some weeks until internal medicine has examined properly what causes my swollen knees […].I've had other symptoms that may have been related to Eliquis right from the beginning.”
Theme 2: Attitudes towards changes in therapy attributes
“I decided to go off the rivaroxaban on my own because I really was, and am, worried about the side effects. I have visited an intuitive healer who recommended me a naturopathic product Nattokinase. I also started taking magnesium and probiotics based on the literature I have read over the internet.” “I can eat again everything from my vegetable garden.[…] With warfarin everything was so complicated.” “changed to warfarin after having open heart surgery, the doctor wanted me to be on this instead. I am finding it very complicated. […]. It is also very challenging when I was travelling in Greece, it is so difficult to get tests done in a different country.” “I used to be on warfarin and although the blood tests were a nuisance, at least I knew where I was at. Now with this one I have no idea if the blood clotting is prevented properly or not.” “I like Xarelto a lot more than Pradaxa because of the pill is smaller and it does not leave a bad taste in my mouth. Pradaxa pills are too big and hard to swallow.”
Theme 3: Challenges with taking medications after therapy change
“I take what I need to. I'm just following what the doctor says.” “They are going to do an ablation on me so hopefully I won't need anticoagulants afterwards.” “The second dose of the day is still difficult to remember. That's the one I've missed couple of times.” “With Eliquis I cut down my dosage to 1 pill a day. I was told by the nurses that I should not do that, that the effect is not going to last long enough.” “This is now twice a day, but it does not matter because I take other medication twice a day.”
Theme 4: Relief from perceived burden of medications after discontinuation
Theme 5: Patients' limited involvement in decision making
“I take vitamin pills and other medication so adding one pill to my evening routine was not a big thing. Of course, once a day would be easier with any medication.” “I am not anxious at all about not taking it anymore, my body tells me what condition I am in and I am doing a lot of exercise and eating the right food.” “I'm just happy it turned out this way. Of course, atrial fibrillation may come back and I may end up on this medication again. But for now, I'm just having my normal life and exercise as usual.” “I saw a NP [nurse practitioner], she left the room to confirm with the cardiologist, and she came back and said “the doctor feels you should try warfarin”. She said “You cannot go back on this and with the way you've been bleeding, you have to change your medication.” And she had mentioned two other medications prior, she asked me what I thought about them, she told me all about them etc. But when she came back from … after talking with the cardiologist, or whoever she spoke to, believed that I should not try the two other medications, I should try warfarin. So I didn't have a face-to-face conversation with cardiologist at that time. I may had argued the point but you cannot have an argument going on with one [person] going back and forth, back and forth.” (continued on next page) 3
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Table 2 (continued) Theme
Representative quote
“I'm not so sure why I was changed to warfarin from Eliquis, but here I am, taking now warfarin. They told me not to eat anything with vitamin K. So soon there's nothing I can eat, I guess.” “GP [general practitioner] didn't talk about NOAC options and didn't seem to know much about how to choose one, but had samples of apixaban on hand, so that's what I got, and a prescription for more.”
Theme 6: Inadequate education and follow up
“he [doctor] persuaded me to be on Eliquis. Mostly because his 80-year old father is on it and it is the best choice when warfarin is not possible, and as it happened, when I was at the doctor's room, the rep came in and gave him a bunch of Eliquis packages.” “I often find that a lot of information is not given by my GP, like I phoned several times the cardiac clinic to discuss my options.” “I had such awful experience with warfarin. […] I had some thing in my mouth and it burst and bled hours. It was scary! so I went back to Eliquis although it is so expensive. Yes, my opinions have changed because they [doctors] don't have enough information about the meds, they did not tell me beforehand that I could have a bleeding in my eye.” “I'm just so unclear what happens to me next: am I going to be on this medication for rest of my life? Is my stroke risk increased because my heart has enlarged or because I have implants in my bones or what. It's not that nobody knows, I think it's just that they don't tell me clearly why I am on warfarin still after all the operations.”
were not happy with the switch. Having to wait for instructions, fear of needles, nurses’ inability to find the vein and the anticipated subsequent bruising, long waiting times at the clinic and having to go for blood tests when on vacation were the specific reasons patients disliked doing the INR tests. Alternatively, some patients-mostly those with prior warfarin experience who were switched to NOACs-expressed concerns around “losing control,” since without the INR test they had no way of telling if their medication is working or not. Other concerns among patients who switched from warfarin to a NOAC were unavailability of antidote for NOACs, their higher price, and lack of evidence on their long-term effects since NOACs have only been around for a few years. Other changes in therapy attributes that were raised by patients were changes in pill size (and hence difficulty in swallowing), bad taste, and packaging. Several participants were indifferent about their therapy change and valued the prescriber's recommendation over their own preferences about the medications. They regarded their stroke prevention medication as something that they “just had to do.” Some participants also expressed that they do not feel there is much difference between warfarin and NOACs and, hence, did not mind the change in the therapy.
decision making, and 6. Inadequate education and follow-up. A summary of the emerged themes and representative participant quotes are provided below to illustrate the results (see Table 2). Theme 1: Reasons for switch or discontinuation of therapy The most common reasons for prescriber-initiated changes were clinical judgments including stroke risk reassessment, labile International Normalized Ratio (INR), medication interactions, comorbidities (gastro-esophageal reflux disease, infection, decline in kidney or liver function), and need for surgery. However, reasons for which patients requested switches or discontinuations included: lack of affordability of the prescribed drug, incompatibility of the drug with the patient's lifestyle, and adverse events or experiences which they attributed to their OAC including headache, allergy, knee swelling, joint or body pain, bad mood, chest pressure, slow healing of a meniscal tear, rosacea, osteoarthritis flare ups, lack of energy, itch and rash. Sometimes, when adverse events were experienced, patients wanted to take matters in their own hands because “taking the medication as prescribed didn't make sense anymore.” Actions taken by patients included: requesting their care provider for a switch or discontinuation of the OAC, discontinuing therapy on their own or reducing the dose without consulting with their care provider. This was not confined to experienced side effects; patients sometimes requested a therapy change or discontinued their therapy on their own due to anticipated future side effects.
Theme 3: Challenges with taking medications after therapy change Overall, participants expressed strong preferences for not taking any medications at all and for once-daily dosing over twice-daily dosing if they absolutely had to take medications. Patients mentioned having difficulty remembering the second (evening) dose of their medication after being switched from a once-daily dosed medication (e.g. warfarin) to a twice-daily dosed one (e.g. apixaban). Some patients addressed this by purposely skipping the second daily dose or by taking both doses at the same time in the morning. Patients did not employ any additional strategies to remember the second dose of their medications when switched from once to twicedaily dosed medication. Patients who didn't mind the twice-daily dosing had other medications that were taken twice a day. Patients also brought up medication-taking challenges specific to warfarin, mainly
Theme 2: Attitudes towards changes in therapy attributes A wide spectrum of perspectives was found regarding the phenomenon of anticoagulant therapy change. A prominent theme among patients who switched from warfarin to NOAC was expression of satisfaction with the reduced complexity of regimen such as not having to watch their diet or go for blood tests. The complications of warfarin were also mentioned by patients who were switched from NOACs to warfarin. The new obligation to go for blood tests was a reason they 4
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remembering what dose to take.
up. This study focused on an aspect of AF care that has never been explored before and, hence, provides important insights that could enable care providers to improve AF stroke prevention care. Below, the main findings under each theme are discussed. Many reasons were identified under theme 1 for switch or discontinuation of therapy. Notably, these were mostly objective and clinical in clinician-initiated therapy changes but subjective in patientinitiated therapy changes. This highlights the importance of patients’ subjective experiences in their decision of taking a medication. The significant changes in therapy attributes was noted by patients when switched between OAC classes (theme 2). Patients’ reactions to these changes was diverse (satisfaction, fear, and indifference). This was expected given the highly variable therapy values and preferences among of patient population.43 These findings further highlight the need for individualizing stroke prevention therapy for AF patients which cannot come true without shared decision making. Another finding of note of this study was that patients face adherence challenges after switching from a once-daily to a twice-daily dosed medication, revealing the need for targeted adherence interventions (theme 3). Although, an overall negative attitude towards taking medications among our study cohort was evident from their expressed relief after therapy discontinuation, and a desire among some to replace medications with natural alternatives (theme 4), perhaps stemming from the “natural is always better” misconception that has previously been reported among this patient population.44,45 Patients expressed dissatisfaction with lack of involvement in the decision-making. While the absence of shared-decision making has been reported in the context of AF stroke prevention before, it is particularly concerning in our study because all of our participants were receiving multi-disciplinary care from specialized AF clinics which offer more attention and time than the majority of AF patients receive in usual care.15 The perceived absence of shared decision-making may however be due to mismatch in expectations between patients and clinicians.46,47 A study found that AF patients often report a paternalistic model of decision-making during consultation, whereas clinicians involved in the same discussions report shared decision-making.46 Moreover, some of the data captured may have reflected experiences with the general practitioners and not the AF clinics, as many patients get started on OAC in community before referral to AF clinics. Nevertheless, patients’ expressed feelings of coercion and subsequent requests for changes in therapy due to its incompatibility with their values and preferences suggests that better work should be done on involving patients in decision-making. Inadequate education and follow up during and after therapy change were another finding of this study (theme 6). The misconceptions around discontinuing OACs after ablation (theme 4), unawareness of adverse effects of prescribed medications (theme 1), misattribution of negative experiences to OACs (theme 1), along with the self-reported lack of knowledge regarding the rationale for their therapy is in line with previous research and emphasizes the important role of counselling when initiating or switching therapy.44,45 Patients’ subjective experiences with OAC therapy change and the decision-making associated with it seems to be affecting their adherence, persistence, as well as their perception of their care provider, the healthcare system, and medications. Most of the issues identified in this study could, however, potentially be mitigated and addressed through shared decision-making and improved patient education/ counselling, potentially leading to higher therapy satisfaction, improved adherence, and, in turn, fewer strokes and bleeding events.48
Theme 4: Relief from perceived burden of medications after discontinuation All patients whose OAC was discontinued expressed happiness for being off of the medications. The most common reasons for this were not having to tolerate the side effects of the medications, ability to go ahead with surgeries that would not otherwise take place, and not having to take so many pills. The expression of relief was more prominent among warfarin users, since they did not have to go for blood tests or watch their diet anymore. Even those patients who were off OAC temporarily (switched to antiplatelets or temporary discontinuation of OAC due to ablation) were hopeful they could stop the anticoagulant. Patients acknowledged that they may be re-prescribed anticoagulants at some point in the future as they age but were happy with any number of days they could get with no medications. It appeared that patients’ satisfaction about being off OACs superseded their anxiety and concerns about having a stroke. For some, this was because they believed they could protect themselves from stroke by eating the “right food” and exercising or using “natural” blood thinners. Theme 5: Patients’ limited involvement in decision-making Several patients expressed dissatisfaction with their lack of involvement in the decision-making process that preceded their therapy change. Some admitted to having no knowledge of the rationale for their therapy change or their doctor's choice of the specific anticoagulant over the other available options. This lack of involvement in decision-making often led to patients ending up with a medication that was not aligned with their values and preferences and to dissatisfaction with therapy, in some cases leading to yet another change in therapy or discontinuation of therapy. In one case, for example, the patient was switched from warfarin to apixaban with no discussion around their ability to afford the medication. The patient simply never filled the prescription and stopped taking anticoagulants. Some patients felt coerced and pressured into the therapy choice. The following phrases were commonly used by participants: “persuaded me”, “pressured me”, “doctor insisted”, and “I was told to.” Excluding patients from the decision-making process also led to patients assuming ulterior motives for prescribing the drug (e.g. relationship with the pharmaceutical representatives) or lack of prescriber knowledge. Some however preferred the paternalistic approach, accepting the physician as the sole decision maker because “He knows best.” Theme 6: Inadequate education and follow up Patients expressed dissatisfaction with the amount of information provided to them by their care providers not just during the therapy decision-making but specifically after the therapy change. Participants complained about not being informed of the possible adverse effects of the new OAC. They believed it was not appropriate to be told to take a medication for the rest of their lives and believed risk reassessment needed to be performed frequently to assess whether they can discontinue OACs. They also felt unsupported after therapy changes because of lack of follow up with them to see how they were doing on the new medication. Discussion This study provides a unique evaluation of AF patients' experiences of OAC therapy change and the associated decision-making. Five themes emerged from the data including: reasons for switch or discontinuation of therapy, attitude towards changes in therapy attributes, challenges with taking medications after therapy change, relief from perceived burden of medications after discontinuation, patients’ limited involvement in decision-making, and inadequate education and follow
Strengths and limitations Analyzing 171 interviews involving 56 patients produced rich data that gave us insights into the therapeutic decision-making process and patients' experiences surrounding it. The longitudinal design of the study and relatively large initial sample from which switch or 5
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discontinuation events were identified offered a unique opportunity to study this phenomenon, which would otherwise be difficult to study. The longitudinal collection of data at frequent intervals ensured that participants’ thoughts and feelings were captured fairly close to the therapy change incidents, reducing recall biases. Limitations that could potentially have affected results in unknown ways include: having multiple interviewers and not recording the interviews, both of which were necessary for feasibility of the study given the huge number of interviews conducted (388 participants, each with multiple interviews). The findings of this study should be interpreted and generalized with caution since participants were recruited from specialized AF clinics. It is unclear how their experiences may have differed from those cared for by general practitioners or in general cardiology practices. Further, response bias cannot be ruled out in this study. There is a possibility that participants who were dissatisfied with their therapy or had negative experiences with changes in their therapy have expressed their opinions more and discussed their experience in detail while those who had positive experiences did not feel the need to discuss what they appreciate about their therapy.
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Conclusion AF patients reported many negative experiences with OAC change and the decision-making associated with it, which seem to affect their adherence, persistence as well as their perception of their care provider, the healthcare system, and medications. Improved shared decisionmaking and patient counselling may result in higher therapy satisfaction, improved adherence, and, in turn, fewer strokes and bleeding events. Funding The Canadian Cardiovascular Society (CCS) Atrial Fibrillation Research Award funded the prospective observational study from which the cohort for this study was chosen. Dr. Loewen's research is partially supported by the UBC David H MacDonald Professorship in Clinical Pharmacy. CRediT authorship contribution statement Shahrzad Salmasi: Conceptualization, Formal analysis, Investigation, Methodology, Software, Validation, Visualization, Writing - original draft, Writing - review & editing. Anita I. Kapanen: Data curation, Investigation, Supervision, Project administration, Writing - review & editing. Leanne Kwan: Investigation, Writing - review & editing, Supervision, Resources, Funding acquisition. Jason G. Andrade: Writing - review & editing, Supervision, Resources. Mary A. De Vera: Methodology, Writing - review & editing, Funding acquisition. Peter Loewen: Conceptualization, Methodology, Formal analysis, Writing - original draft, Writing - review & editing, Funding acquisition, Supervision, Project administration. Declaration of competing interest None of the authors have any conflicts to declare. Acknowledgements We are grateful to Jenny MacGillivray, Clarene Ho, Donna Rigollet, Lindsey Ward, Betty Reid-Girard, Moira Whittle, Liz Mulvaney, Jacqueline Lum, Tracy Gwozd, Belinda-Ann Furlan, Serena Kutcher, Stephanie Hsieh, Jenelle Rogers/Haas, Sonia Basi, Margaret Sidsworth, Mary Elliot, Bonnie Wong, Pamela Colley, Nicole Gorman, and Louann Janicki for their assistance in identifying and recruiting patients. We are also grateful to Dr Heather Jackson and CSBC for their support. Finally, we thank the Canadian Cardiovascular Society for funding this 6
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S. Salmasi, et al. 22. Lee VWY, Tam CS, Yan BP, et al. Barriers to warfarin use for stroke prevention in patients with atrial fibrillation in Hong Kong. Clin Cardiol. 2013;36(3):166–171. https://doi.org/10.1002/clc.22077. 23. Rewiuk K, Bednarz S, Faryan P, et al. Knowledge of antithrombotic prophylaxis among patients with atrial fibrillation. Cardiol J. 2007;14(1):44–49. 24. Smith MB, Christensen N, Wang S, et al. Warfarin knowledge in patients with atrial fibrillation: implications for safety, efficacy, and education strategies. Cardiology. 2010;116(1):61–69. https://doi.org/10.1159/000314936. 25. St-Louis L, Robichaud-Ekstrand S. Knowledge level and coping strategies according to coagulation levels in older persons with atrial fibrillation. Nurs Health Sci. 2003;5(1):67–75. https://doi.org/10.1046/j.1442-2018.2003.00136.x. 26. Frankel DS, Parker SE, Rosenfeld LE, et al. Hrs/nsa 2014 survey of atrial fibrillation and stroke: gaps in knowledge and perspective, opportunities for improvement. Austin J Cerebrovasc Dis Stroke. 2015;24(8):1691–1700. https://doi.org/10.1016/j. jstrokecerebrovasdis.2015.06.026. 27. Douros A, Renoux C, Coulombe J, et al. Patterns of long-term use of non-vitamin k antagonist oral anticoagulants for non-valvular atrial fibrillation: quebec observational study. Pharmacoepidemiol Drug Saf. 2017;26(12):1546–1554. https://doi.org/ 10.1002/pds.4333. 28. Coleman CI, Tangirala M, Evers T. Treatment persistence and discontinuation with rivaroxaban, dabigatran, and warfarin for stroke prevention in patients with nonvalvular atrial fibrillation in the United States. PLoS One. 2016;11(6):e0157769https://doi.org/10.1371/journal.pone.0157769. 29. Collings SL, Lefevre C, Johnson ME, et al. Oral anticoagulant persistence in patients with non-valvular atrial fibrillation: a cohort study using primary care data in Germany. PLoS One. 2017;12(10):e0185642https://doi.org/10.1371/journal.pone. 0185642. 30. Fang MC, Go AS, Chang Y, et al. Warfarin discontinuation after starting warfarin for atrial fibrillation. Circ Cardiovasc Qual Outcomes. 2010;3(6):624–631. https://doi. org/10.1161/circoutcomes.110.937680. 31. Jackevicius CA, Tsadok MA, Essebag V, et al. Early non-persistence with dabigatran and rivaroxaban in patients with atrial fibrillation. Heart (British Cardiac Society). 2017;103(17):1331–1338. https://doi.org/10.1136/heartjnl-2016-310672. 32. Jackson 2nd LR, Kim S, Shrader P, et al. Early therapeutic persistence on dabigatran versus warfarin therapy in patients with atrial fibrillation: results from the outcomes registry for better informed treatment of atrial fibrillation (orbit-af) registry. J Thromb Thrombolysis. 2018;46(4):435–439. https://doi.org/10.1007/s11239-0181715-1. 33. Lip GYH, Pan X, Kamble S, et al. Discontinuation risk comparison among 'real-world' newly anticoagulated atrial fibrillation patients: apixaban, warfarin, dabigatran, or rivaroxaban. PLoS One. 2018;13(4):e0195950https://doi.org/10.1371/journal.pone. 0195950. 34. O'brien EC, Simon DN, Allen LA, et al. Reasons for warfarin discontinuation in the outcomes registry for better informed treatment of atrial fibrillation (orbit-af). Am
Heart J. 2014;168(4):487–494. https://doi.org/10.1016/j.ahj.2014.07.002. 35. Wu S, Xie S, Xu Y, et al. Persistence and outcomes of non‐vitamin k antagonist oral anticoagulants versus warfarin in patients with non‐valvular atrial fibrillation. J Clin Nurs. 2019. https://doi.org/10.1111/jocn.14797. 36. Leventhal H, Meyer D, Nerenz D. The common sense model of illness danger. J Soc Distress Homeless. 1980;2:7–30. 37. Janz NK, Becker MH. The health belief model: a decade later. Health Educ Q. 1984;11(1):1–47. https://doi.org/10.1177/109019818401100101. 38. Howitt A, Armstrong D. Implementing evidence based medicine in general practice: audit and qualitative study of antithrombotic treatment for atrial fibrillation. BMJ. 1999;318(7194):1324–1327. https://doi.org/10.1136/bmj.318.7194.1324. 39. Fuller R, Dudley N, Blacktop J. Avoidance hierarchies and preferences for anticoagulation–semi-qualitative analysis of older patients' views about stroke prevention and the use of warfarin. Age Ageing. 2004;33(6):608–611. https://doi.org/10.1093/ ageing/afh202. 40. Lipman T, Murtagh MJ, Thomson R. How research-conscious gps make decisions about anticoagulation in patients with atrial fibrillation: a qualitative study. Fam Pract. 2004;21(3):290–298. https://doi.org/10.1093/fampra/cmh313. 41. Tong A, Sainsbury P, Craig J. Consolidated criteria for reporting qualitative research (coreq): a 32-item checklist for interviews and focus groups. Int J Qual Health Care. 2007;19(6):349–357. https://doi.org/10.1093/intqhc/mzm042. 42. Braun V, Clarke V. Using thematic analysis in psychology. Qual Res Psychol. 2006;3(2):77–101. https://doi.org/10.1191/1478088706qp063oa. 43. Loewen P, Ji A, Kapanen A, et al. Patient values and preferences for antithrombotic therapy for stroke prevention in af: a systematic review. CJC. 2016;32(10):S257–S258. https://doi.org/10.1016/j.cjca.2016.07.416. 44. Salmasi S, De Vera MA, Barry A, et al. Assessment of condition and medication knowledge gaps among atrial fibrillation patients: a systematic review and metaanalysis. Ann Pharmacother. 2019. https://doi.org/10.1177/1060028019835845 0(0):1060028019835845. 45. Salmasi S, Kwan L, Macgillivray J, et al. Assessment of atrial fibrillation patients' education needs from patient and clinician perspectives: a qualitative descriptive study. Thromb Res. 2018. https://doi.org/10.1016/j.thromres.2018.11.015. 46. Borg Xuereb C, Shaw RL, Lane DA. Patients' and health professionals' views and experiences of atrial fibrillation and oral-anticoagulant therapy: a qualitative metasynthesis. Patient Educ Couns. 2012;88(2):330–337. https://doi.org/10.1016/j.pec. 2012.05.011. 47. Andrade JG, Krahn AD, Skanes AC, et al. Values and preferences of physicians and patients with nonvalvular atrial fibrillation who receive oral anticoagulation therapy for stroke prevention. Can J Cardiol. 2016;32(6):747–753. https://doi.org/10.1016/ j.cjca.2015.09.023. 48. Shay LA, Lafata JE. Where is the evidence? A systematic review of shared decision making and patient outcomes. Med Decis Mak. 2015;35(1):114–131. https://doi.org/ 10.1177/0272989X14551638.
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Contents lists available at ScienceDirect
Research in Social and Administrative Pharmacy journal homepage: www.elsevier.com/locate/rsap
Atrial fibrillation patients’ experiences and perspectives of anticoagulation therapy changes Shahrzad Salmasia,b, Anita I. Kapanena,b, Leanne Kwanc, Jason G. Andraded,e, Mary A. De Veraa,b, Peter Loewena,b,∗ a
Collaboration for Outcomes Research and Evaluation (CORE), University of British Columbia, Vancouver, Canada Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, Canada c Atrial Fibrillation Clinic, Royal Columbian Hospital, New Westminster, Canada d Atrial Fibrillation Clinic, Vancouver General Hospital, Vancouver, Canada e Department of Medicine, Faculty of Medicine, University of British Columbia, Vancouver, Canada b
ABSTRACT
Background: Atrial fibrillation (AF) patients’ experiences with changes in their oral anticoagulant (OAC) therapy are understudied. Objective: The objective of this study was to qualitatively describe AF patients’ experiences and perspectives of changes made to their OAC therapy (switches or discontinuations). Methods: A thematic analysis was performed on systematically-collected qualitative data from AF patients who experienced a therapy change (switching or discontinuing an OAC) as part of their participation in a large 2-year prospective observational study. Results: A total of 56 participants met the inclusion criteria. Six themes emerged from the data: 1. reasons for switch or discontinuation of therapy, 2. attitudes towards changes in therapy attributes, 3. challenges with taking medications after therapy change, 4. relief from perceived burden of medication after discontinuation, 5. patients’ limited involvement in decision-making, and 6. inadequate education and follow up. Patients were found to request changes in therapy based on their subjective experience with it (rather than clinically justified reasons). They were found to have limited knowledge about their medications, differing reactions to changes in their therapy attributes after a switch, an overall negative attitude towards taking medications, adherence challenges after switching from once daily to twice daily medication, feelings of being excluded from the decision-making process about their therapy changes and feelings of being unsupported after these changes. Conclusions: There are clear opportunities to improve patients’ experiences with OAC therapy changes through improved shared decision-making and patient education/counselling.
Background Atrial fibrillation (AF) is the most common clinically significant arrhythmia, and a very potent risk factor for stroke.1–5 Oral anticoagulants (OACs), including warfarin and non-vitamin K oral anticoagulants (NOACs: apixaban, dabigatran, edoxaban, and rivaroxaban) are very effective for stroke prevention in AF patients.1,6–10 OAC prescribing in AF is influenced by a complex matrix of patient and prescriber factors, reimbursement policies, and medication attributes including efficacy, bleeding risk, dosing regimen, monitoring requirements, cost, and antidote availability. Patients also have personal values and preferences related to AF stroke prevention which they are not always able to clarify and effectively communicate to the prescriber.11–26 The process to find the most appropriate OAC for a particular patient, therefore, often involves a trial and error period including switches between OACs. Limited evidence suggests that over 30% of AF
∗
patients experience a switch in therapy.27 It is also not uncommon for patients to experience temporary or permanent discontinuation (e.g. following serious bleeding or stroke risk reassessment or due to surgical procedures, or acute conditions that increase risk of bleeding) of their OACs.28–35 Established psychological and behavioral-change theories (e.g. the health belief model, the common-sense model) have linked patients' perception, beliefs and experiences with therapy to their behaviors such as medication adherence.36,37 These common therapy changes have not been studied from patients' perspective. Patients' experiences, beliefs, and perceptions have been shown to be directly associated with therapy satisfaction and adherence.15,38–40 The objective of this exploratory study was to qualitatively describe AF patients’ subjective experiences with changes made to their OAC therapy.
Corresponding author. Faculty of Pharmaceutical Sciences, The University of British Columbia, 2405 Wesbrook Mall, Vancouver, BC, V6T 1Z3, Canada. E-mail address: [email protected] (P. Loewen).
https://doi.org/10.1016/j.sapharm.2020.01.004 Received 18 September 2019; Received in revised form 2 January 2020; Accepted 12 January 2020 1551-7411/ © 2020 Published by Elsevier Inc.
Please cite this article as: Shahrzad Salmasi, et al., Research in Social and Administrative Pharmacy, https://doi.org/10.1016/j.sapharm.2020.01.004
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Methods
Data analysis
A multicenter, prospective, longitudinal cohort study was conducted at British Columbia's (UBC) five specialized AF clinics. The qualitative data collected from a subgroup of participants in that study who experienced a change (switch or discontinuation) in their OAC therapy was retrospectively analyzed. Ethical approval was granted by the research ethics boards of the University of British Columbia, Interior Health, Fraser Health, Vancouver Island Health, Providence Health, and Vancouver Coastal Health.41
For every participant, a summary of their clinical case was prepared which involved their index OAC, current OAC, reason for switch, records of discontinuations with reason to provide the context in which their responses were interpreted. The data were analyzed using inductive qualitative thematic analysis following the steps recommended by Braun and colleagues.42 Analysis involved 1.data immersion: reading the responses several times; 2.code generation: line by line freecoding with as many codes as needed and 3. theme generation: assessing the homogeneity and heterogeneity between the codes to group them under categories and identify themes; and 4. reviewing themes to ensure coherence of data within themes, and clear and identifiable distinctions between themes.42 Data were coded by one researcher; however coding was frequently discussed with and reviewed by the senior author. The reporting of this study follows the COREQ recommendations (checklist attached).
Study design The longitudinal study enrolled 388 AF patients prescribed OACs. Participants were followed prospectively with quarterly telephone interviews for 2 years, or until patients dropped out, permanently discontinued OAC therapy, or died, whichever came first. Every phone interview was referred to as a “study visit” and conducted without the presence of nonparticipants. The interviewers were undergraduate and graduate pharmacy students or the study coordinator (PhD) who were not involved in the care of the patient. The interview questions were developed by the study team based on their clinical and research experience with AF patients. All interviewers were trained by the study coordinator (AK), observed for their first interview, and given feedback before conducting interviews independently. At every study visit the following open-ended questions were asked: 1) Have your feelings about your medication changed since we last talked?; 2) What kinds of things, if any, make it difficult to take your [name of OAC] as prescribed?; 3) Why do you think it is important to take your medication as prescribed?; 4) Are you happy with the number of daily doses, or would you have preferred something else?; and 5) What, if anything, could help you take your [name of OAC] more consistently? In every visit, patients were also asked if the name or dose of their OAC had changed since the previous visit. If a patient reported having switched medications or discontinued therapy, they were asked the following additional openended questions to capture their experiences about the change: Tell me the whole story on why or how the therapy was switched or stopped; and so far, how is it going for you since the change? Participants were also invited to share any additional thoughts they had at the end of each study visit. Detailed notes, including quotations, wherever possible, were taken by the interviewer during the interview. The data were entered into the study electronic database within half an hour of the completion of the interview. The responses were not processed or analyzed until the completion of the study.
Results Of the 388 patients recruited, 56 experienced a switch or discontinuation of therapy, over a mean follow-up of 14.5 (SD = 6.0) months, forming the target sample of this qualitative study (Table 1). The majority were male (71.4%), married (71%), and Caucasian (88%) with mean age of 66.6 years (SD = 9.6). The study population represented 33 switches between OACs (6 switches between NOACs, 11 from NOAC to warfarin, and 16 from warfarin to NOAC) and 25 therapy discontinuations. Data from 171 interviews across the 56 included patients were used in the qualitative analysis, leading to emergence of six themes: 1. Reasons for switch or discontinuation of therapy, 2. Attitudes towards changes in therapy attributes, 3. Challenges with medication taking after therapy change, 4. Relief from perceived burden of medication after discontinuation, 5. Patients’ limited involvement in Table 1 Characteristic of the included participants.
Participants This qualitative study focused on participants who underwent a change in anticoagulant therapy (switch or discontinuation). Therapy changes could be patient- or clinician-initiated. Switches were defined as changing from one OAC to another. Therapy discontinuation was defined as temporary or permanent discontinuation of OAC therapy, including switching to antiplatelet therapy. Data processing Demographic and clinical information and answers to open-ended questions were extracted from the online survey tool for participants who, at any point during the study, experienced a switch or discontinuation of their OAC therapy. Interview data were extracted for all study visits of the eligible participant (from cohort entry until end of follow up); not just the study visit in which therapy change was identified. Data were exported to Nvivo software® (QSR International Pty Ltd. Version 12) for analysis.
Characteristics
N (%) unless otherwise stated
CHA2DS2-VASca, Mean (SD) HASBLEDb, Mean (SD) Age, Mean (SD) AF type Paroxysmal Persistent Long term persistent Permanent Unknown Sex (Male) Highest education level achieved Elementary High school or equivalent Vocational/technical school Some college/university Undergraduate college/university degree Graduate or professional degree Race Other Caucasian/White Marital status Single/Never married Common-law/married
2.5 (1.6) 1.4 (0.9) 66.6 (9.6) 35 (62.5) 8 (14.3) 5 (8.9) 5 (8.9) 3 (5.4) 40 (71.4) 2 (3.6) 10 (17.9) 4 (7.1) 18 (32.1) 12 (21.4) 10 (17.9) 7 (12.5) 49 (87.5) 16 (28.6) 40 (71.4)
a CHA2DS2-VASc: stroke risk score calculated based on presence of comorbidities. Cardiomyopathy (1 score), Hypertension (1 score), Age≥75(2 scores), Diabetes (1 score), Stroke (2 scores), Vascular disease (1 score), Age 65–75 (1 score), Sex category female(1 score). b HASBLED: bleeding risk score calculated based on presence of comorbidities: Hypertension (1 score), Abnormal liver/kidney function (1 score), Stroke (1 score), Bleeding(1 score), Labile INR(1 score), Elderly > 75 years(1 score), Drugs or alcohol use(1 score).
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Table 2 Representative patient quotes. Theme Theme 1: Reasons for switching/stopping
Representative quote
“I had back pain in May and I thought it might have been due to Xarelto.[…]. They said it was due to arthritis pain in my neck, not because of the medication.” “I couldn't stand the itch and rash, so I stopped three weeks ago to take it [OAC], skin reaction reduced but I took one pill two days ago and now I'm on really bad itch again, so this blood thinner is not doing any good for me.” “I thought I had a rash and swelling in my feet from it when I was in Greece however it was determined not to be caused by warfarin” “Yes, now I'm off of it for some weeks until internal medicine has examined properly what causes my swollen knees […].I've had other symptoms that may have been related to Eliquis right from the beginning.”
Theme 2: Attitudes towards changes in therapy attributes
“I decided to go off the rivaroxaban on my own because I really was, and am, worried about the side effects. I have visited an intuitive healer who recommended me a naturopathic product Nattokinase. I also started taking magnesium and probiotics based on the literature I have read over the internet.” “I can eat again everything from my vegetable garden.[…] With warfarin everything was so complicated.” “changed to warfarin after having open heart surgery, the doctor wanted me to be on this instead. I am finding it very complicated. […]. It is also very challenging when I was travelling in Greece, it is so difficult to get tests done in a different country.” “I used to be on warfarin and although the blood tests were a nuisance, at least I knew where I was at. Now with this one I have no idea if the blood clotting is prevented properly or not.” “I like Xarelto a lot more than Pradaxa because of the pill is smaller and it does not leave a bad taste in my mouth. Pradaxa pills are too big and hard to swallow.”
Theme 3: Challenges with taking medications after therapy change
“I take what I need to. I'm just following what the doctor says.” “They are going to do an ablation on me so hopefully I won't need anticoagulants afterwards.” “The second dose of the day is still difficult to remember. That's the one I've missed couple of times.” “With Eliquis I cut down my dosage to 1 pill a day. I was told by the nurses that I should not do that, that the effect is not going to last long enough.” “This is now twice a day, but it does not matter because I take other medication twice a day.”
Theme 4: Relief from perceived burden of medications after discontinuation
Theme 5: Patients' limited involvement in decision making
“I take vitamin pills and other medication so adding one pill to my evening routine was not a big thing. Of course, once a day would be easier with any medication.” “I am not anxious at all about not taking it anymore, my body tells me what condition I am in and I am doing a lot of exercise and eating the right food.” “I'm just happy it turned out this way. Of course, atrial fibrillation may come back and I may end up on this medication again. But for now, I'm just having my normal life and exercise as usual.” “I saw a NP [nurse practitioner], she left the room to confirm with the cardiologist, and she came back and said “the doctor feels you should try warfarin”. She said “You cannot go back on this and with the way you've been bleeding, you have to change your medication.” And she had mentioned two other medications prior, she asked me what I thought about them, she told me all about them etc. But when she came back from … after talking with the cardiologist, or whoever she spoke to, believed that I should not try the two other medications, I should try warfarin. So I didn't have a face-to-face conversation with cardiologist at that time. I may had argued the point but you cannot have an argument going on with one [person] going back and forth, back and forth.” (continued on next page) 3
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Table 2 (continued) Theme
Representative quote
“I'm not so sure why I was changed to warfarin from Eliquis, but here I am, taking now warfarin. They told me not to eat anything with vitamin K. So soon there's nothing I can eat, I guess.” “GP [general practitioner] didn't talk about NOAC options and didn't seem to know much about how to choose one, but had samples of apixaban on hand, so that's what I got, and a prescription for more.”
Theme 6: Inadequate education and follow up
“he [doctor] persuaded me to be on Eliquis. Mostly because his 80-year old father is on it and it is the best choice when warfarin is not possible, and as it happened, when I was at the doctor's room, the rep came in and gave him a bunch of Eliquis packages.” “I often find that a lot of information is not given by my GP, like I phoned several times the cardiac clinic to discuss my options.” “I had such awful experience with warfarin. […] I had some thing in my mouth and it burst and bled hours. It was scary! so I went back to Eliquis although it is so expensive. Yes, my opinions have changed because they [doctors] don't have enough information about the meds, they did not tell me beforehand that I could have a bleeding in my eye.” “I'm just so unclear what happens to me next: am I going to be on this medication for rest of my life? Is my stroke risk increased because my heart has enlarged or because I have implants in my bones or what. It's not that nobody knows, I think it's just that they don't tell me clearly why I am on warfarin still after all the operations.”
were not happy with the switch. Having to wait for instructions, fear of needles, nurses’ inability to find the vein and the anticipated subsequent bruising, long waiting times at the clinic and having to go for blood tests when on vacation were the specific reasons patients disliked doing the INR tests. Alternatively, some patients-mostly those with prior warfarin experience who were switched to NOACs-expressed concerns around “losing control,” since without the INR test they had no way of telling if their medication is working or not. Other concerns among patients who switched from warfarin to a NOAC were unavailability of antidote for NOACs, their higher price, and lack of evidence on their long-term effects since NOACs have only been around for a few years. Other changes in therapy attributes that were raised by patients were changes in pill size (and hence difficulty in swallowing), bad taste, and packaging. Several participants were indifferent about their therapy change and valued the prescriber's recommendation over their own preferences about the medications. They regarded their stroke prevention medication as something that they “just had to do.” Some participants also expressed that they do not feel there is much difference between warfarin and NOACs and, hence, did not mind the change in the therapy.
decision making, and 6. Inadequate education and follow-up. A summary of the emerged themes and representative participant quotes are provided below to illustrate the results (see Table 2). Theme 1: Reasons for switch or discontinuation of therapy The most common reasons for prescriber-initiated changes were clinical judgments including stroke risk reassessment, labile International Normalized Ratio (INR), medication interactions, comorbidities (gastro-esophageal reflux disease, infection, decline in kidney or liver function), and need for surgery. However, reasons for which patients requested switches or discontinuations included: lack of affordability of the prescribed drug, incompatibility of the drug with the patient's lifestyle, and adverse events or experiences which they attributed to their OAC including headache, allergy, knee swelling, joint or body pain, bad mood, chest pressure, slow healing of a meniscal tear, rosacea, osteoarthritis flare ups, lack of energy, itch and rash. Sometimes, when adverse events were experienced, patients wanted to take matters in their own hands because “taking the medication as prescribed didn't make sense anymore.” Actions taken by patients included: requesting their care provider for a switch or discontinuation of the OAC, discontinuing therapy on their own or reducing the dose without consulting with their care provider. This was not confined to experienced side effects; patients sometimes requested a therapy change or discontinued their therapy on their own due to anticipated future side effects.
Theme 3: Challenges with taking medications after therapy change Overall, participants expressed strong preferences for not taking any medications at all and for once-daily dosing over twice-daily dosing if they absolutely had to take medications. Patients mentioned having difficulty remembering the second (evening) dose of their medication after being switched from a once-daily dosed medication (e.g. warfarin) to a twice-daily dosed one (e.g. apixaban). Some patients addressed this by purposely skipping the second daily dose or by taking both doses at the same time in the morning. Patients did not employ any additional strategies to remember the second dose of their medications when switched from once to twicedaily dosed medication. Patients who didn't mind the twice-daily dosing had other medications that were taken twice a day. Patients also brought up medication-taking challenges specific to warfarin, mainly
Theme 2: Attitudes towards changes in therapy attributes A wide spectrum of perspectives was found regarding the phenomenon of anticoagulant therapy change. A prominent theme among patients who switched from warfarin to NOAC was expression of satisfaction with the reduced complexity of regimen such as not having to watch their diet or go for blood tests. The complications of warfarin were also mentioned by patients who were switched from NOACs to warfarin. The new obligation to go for blood tests was a reason they 4
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remembering what dose to take.
up. This study focused on an aspect of AF care that has never been explored before and, hence, provides important insights that could enable care providers to improve AF stroke prevention care. Below, the main findings under each theme are discussed. Many reasons were identified under theme 1 for switch or discontinuation of therapy. Notably, these were mostly objective and clinical in clinician-initiated therapy changes but subjective in patientinitiated therapy changes. This highlights the importance of patients’ subjective experiences in their decision of taking a medication. The significant changes in therapy attributes was noted by patients when switched between OAC classes (theme 2). Patients’ reactions to these changes was diverse (satisfaction, fear, and indifference). This was expected given the highly variable therapy values and preferences among of patient population.43 These findings further highlight the need for individualizing stroke prevention therapy for AF patients which cannot come true without shared decision making. Another finding of note of this study was that patients face adherence challenges after switching from a once-daily to a twice-daily dosed medication, revealing the need for targeted adherence interventions (theme 3). Although, an overall negative attitude towards taking medications among our study cohort was evident from their expressed relief after therapy discontinuation, and a desire among some to replace medications with natural alternatives (theme 4), perhaps stemming from the “natural is always better” misconception that has previously been reported among this patient population.44,45 Patients expressed dissatisfaction with lack of involvement in the decision-making. While the absence of shared-decision making has been reported in the context of AF stroke prevention before, it is particularly concerning in our study because all of our participants were receiving multi-disciplinary care from specialized AF clinics which offer more attention and time than the majority of AF patients receive in usual care.15 The perceived absence of shared decision-making may however be due to mismatch in expectations between patients and clinicians.46,47 A study found that AF patients often report a paternalistic model of decision-making during consultation, whereas clinicians involved in the same discussions report shared decision-making.46 Moreover, some of the data captured may have reflected experiences with the general practitioners and not the AF clinics, as many patients get started on OAC in community before referral to AF clinics. Nevertheless, patients’ expressed feelings of coercion and subsequent requests for changes in therapy due to its incompatibility with their values and preferences suggests that better work should be done on involving patients in decision-making. Inadequate education and follow up during and after therapy change were another finding of this study (theme 6). The misconceptions around discontinuing OACs after ablation (theme 4), unawareness of adverse effects of prescribed medications (theme 1), misattribution of negative experiences to OACs (theme 1), along with the self-reported lack of knowledge regarding the rationale for their therapy is in line with previous research and emphasizes the important role of counselling when initiating or switching therapy.44,45 Patients’ subjective experiences with OAC therapy change and the decision-making associated with it seems to be affecting their adherence, persistence, as well as their perception of their care provider, the healthcare system, and medications. Most of the issues identified in this study could, however, potentially be mitigated and addressed through shared decision-making and improved patient education/ counselling, potentially leading to higher therapy satisfaction, improved adherence, and, in turn, fewer strokes and bleeding events.48
Theme 4: Relief from perceived burden of medications after discontinuation All patients whose OAC was discontinued expressed happiness for being off of the medications. The most common reasons for this were not having to tolerate the side effects of the medications, ability to go ahead with surgeries that would not otherwise take place, and not having to take so many pills. The expression of relief was more prominent among warfarin users, since they did not have to go for blood tests or watch their diet anymore. Even those patients who were off OAC temporarily (switched to antiplatelets or temporary discontinuation of OAC due to ablation) were hopeful they could stop the anticoagulant. Patients acknowledged that they may be re-prescribed anticoagulants at some point in the future as they age but were happy with any number of days they could get with no medications. It appeared that patients’ satisfaction about being off OACs superseded their anxiety and concerns about having a stroke. For some, this was because they believed they could protect themselves from stroke by eating the “right food” and exercising or using “natural” blood thinners. Theme 5: Patients’ limited involvement in decision-making Several patients expressed dissatisfaction with their lack of involvement in the decision-making process that preceded their therapy change. Some admitted to having no knowledge of the rationale for their therapy change or their doctor's choice of the specific anticoagulant over the other available options. This lack of involvement in decision-making often led to patients ending up with a medication that was not aligned with their values and preferences and to dissatisfaction with therapy, in some cases leading to yet another change in therapy or discontinuation of therapy. In one case, for example, the patient was switched from warfarin to apixaban with no discussion around their ability to afford the medication. The patient simply never filled the prescription and stopped taking anticoagulants. Some patients felt coerced and pressured into the therapy choice. The following phrases were commonly used by participants: “persuaded me”, “pressured me”, “doctor insisted”, and “I was told to.” Excluding patients from the decision-making process also led to patients assuming ulterior motives for prescribing the drug (e.g. relationship with the pharmaceutical representatives) or lack of prescriber knowledge. Some however preferred the paternalistic approach, accepting the physician as the sole decision maker because “He knows best.” Theme 6: Inadequate education and follow up Patients expressed dissatisfaction with the amount of information provided to them by their care providers not just during the therapy decision-making but specifically after the therapy change. Participants complained about not being informed of the possible adverse effects of the new OAC. They believed it was not appropriate to be told to take a medication for the rest of their lives and believed risk reassessment needed to be performed frequently to assess whether they can discontinue OACs. They also felt unsupported after therapy changes because of lack of follow up with them to see how they were doing on the new medication. Discussion This study provides a unique evaluation of AF patients' experiences of OAC therapy change and the associated decision-making. Five themes emerged from the data including: reasons for switch or discontinuation of therapy, attitude towards changes in therapy attributes, challenges with taking medications after therapy change, relief from perceived burden of medications after discontinuation, patients’ limited involvement in decision-making, and inadequate education and follow
Strengths and limitations Analyzing 171 interviews involving 56 patients produced rich data that gave us insights into the therapeutic decision-making process and patients' experiences surrounding it. The longitudinal design of the study and relatively large initial sample from which switch or 5
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discontinuation events were identified offered a unique opportunity to study this phenomenon, which would otherwise be difficult to study. The longitudinal collection of data at frequent intervals ensured that participants’ thoughts and feelings were captured fairly close to the therapy change incidents, reducing recall biases. Limitations that could potentially have affected results in unknown ways include: having multiple interviewers and not recording the interviews, both of which were necessary for feasibility of the study given the huge number of interviews conducted (388 participants, each with multiple interviews). The findings of this study should be interpreted and generalized with caution since participants were recruited from specialized AF clinics. It is unclear how their experiences may have differed from those cared for by general practitioners or in general cardiology practices. Further, response bias cannot be ruled out in this study. There is a possibility that participants who were dissatisfied with their therapy or had negative experiences with changes in their therapy have expressed their opinions more and discussed their experience in detail while those who had positive experiences did not feel the need to discuss what they appreciate about their therapy.
study and the patients who participated in this study and trusted us with their stories. Appendix A. Supplementary data Supplementary data to this article can be found online at https:// doi.org/10.1016/j.sapharm.2020.01.004. References 1. You JJ, Singer DE, Howard PA, et al. Antithrombotic therapy for atrial fibrillation: antithrombotic therapy and prevention of thrombosis, 9th ed: American college of chest physicians evidence-based clinical practice guidelines. Chest. 2012;141(2 Suppl):e531S–575S. https://doi.org/10.1378/chest.11-2304. 2. Kirchhof P, Auricchio A, Bax J, et al. Outcome parameters for trials in atrial fibrillation: executive summary. Eur Heart J. 2007;28(22):2803–2817. https://doi.org/ 10.1093/eurheartj/ehm358. 3. Friberg J, Scharling H, Gadsbøll N, et al. Comparison of the impact of atrial fibrillation on the risk of stroke and cardiovascular death in women versus men (the copenhagen city heart study). 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Conclusion AF patients reported many negative experiences with OAC change and the decision-making associated with it, which seem to affect their adherence, persistence as well as their perception of their care provider, the healthcare system, and medications. Improved shared decisionmaking and patient counselling may result in higher therapy satisfaction, improved adherence, and, in turn, fewer strokes and bleeding events. Funding The Canadian Cardiovascular Society (CCS) Atrial Fibrillation Research Award funded the prospective observational study from which the cohort for this study was chosen. Dr. Loewen's research is partially supported by the UBC David H MacDonald Professorship in Clinical Pharmacy. CRediT authorship contribution statement Shahrzad Salmasi: Conceptualization, Formal analysis, Investigation, Methodology, Software, Validation, Visualization, Writing - original draft, Writing - review & editing. Anita I. Kapanen: Data curation, Investigation, Supervision, Project administration, Writing - review & editing. Leanne Kwan: Investigation, Writing - review & editing, Supervision, Resources, Funding acquisition. Jason G. Andrade: Writing - review & editing, Supervision, Resources. Mary A. De Vera: Methodology, Writing - review & editing, Funding acquisition. Peter Loewen: Conceptualization, Methodology, Formal analysis, Writing - original draft, Writing - review & editing, Funding acquisition, Supervision, Project administration. Declaration of competing interest None of the authors have any conflicts to declare. Acknowledgements We are grateful to Jenny MacGillivray, Clarene Ho, Donna Rigollet, Lindsey Ward, Betty Reid-Girard, Moira Whittle, Liz Mulvaney, Jacqueline Lum, Tracy Gwozd, Belinda-Ann Furlan, Serena Kutcher, Stephanie Hsieh, Jenelle Rogers/Haas, Sonia Basi, Margaret Sidsworth, Mary Elliot, Bonnie Wong, Pamela Colley, Nicole Gorman, and Louann Janicki for their assistance in identifying and recruiting patients. We are also grateful to Dr Heather Jackson and CSBC for their support. Finally, we thank the Canadian Cardiovascular Society for funding this 6
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