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Antithrombotic Therapy and Prevention of Thrombosis, 9th Ed: American College of Chest Physician Evidence-Based Clinical Practice Guidelines Online Only Articles |

Patient Values and Preferences in Decision Making for Antithrombotic Therapy: A Systematic ReviewPatient Values for Antithrombotic Therapy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines FREE TO VIEW

Samantha MacLean, MSc; Sohail Mulla, BHSc; Elie A. Akl, MD, MPH, PhD; Milosz Jankowski, MD, PhD; Per Olav Vandvik, MD, PhD; Shanil Ebrahim, MSc; Shelley McLeod, MSc; Neera Bhatnagar, MLIS; Gordon H. Guyatt, MD,FCCP
Author and Funding Information

From the Department of Biostatistics and Clinical Epidemiology (Ms MacLean, Messrs Mulla and Ebrahim, and Drs Akl and Guyatt) and Health Sciences Library (Ms Bhatnagar), McMaster University, Hamilton, ON, Canada; Department of Internal Medicine (Dr Jankowski), Faculty of Medicine, Jagiellonian University Medical College, Krakow, Poland; Division of Emergency Medicine (Ms McLeod), Department of Medicine, Schulich School of Medicine and Dentistry, The University of Western Ontario, London, ON, Canada; Department of Medicine (Dr Akl), State University of New York at Buffalo, Buffalo, NY; and Norwegian Knowledge Centre for the Health Services and Department of Medicine Gjøvik (Dr Vandvik), Innlandet Hospital Trust, Gjøvik, Norway.

Correspondence to: Samantha MacLean, MSc, McMaster University, 1200 Main St W, Hamilton, ON, L8N 3Z5, Canada; e-mail: macleast@mcmaster.ca


Ms MacLean is currently at the University of British Columbia, Faculty of Medicine, School of Population of Public Health.

Funding/Support: The Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines received support from the National Heart, Lung, and Blood Institute [R13 HL104758] and Bayer Schering Pharma AG. Support in the form of educational grants was also provided by Bristol-Myers Squibb; Pfizer, Inc; Canyon Pharmaceuticals; and sanofi-aventis US.

Disclaimer: American College of Chest Physician guidelines are intended for general information only, are not medical advice, and do not replace professional medical care and physician advice, which always should be sought for any medical condition. The complete disclaimer for this guideline can be accessed at http://chestjournal.chestpubs.org/content/141/2_suppl/1S.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (http://www.chestpubs.org/site/misc/reprints.xhtml).


Chest. 2012;141(2_suppl):e1S-e23S. doi:10.1378/chest.11-2290
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Background:  Development of clinical practice guidelines involves making trade-offs between desirable and undesirable consequences of alternative management strategies. Although the relative value of health states to patients should provide the basis for these trade-offs, few guidelines have systematically summarized the relevant evidence. We conducted a systematic review relating to values and preferences of patients considering antithrombotic therapy.

Methods:  We included studies examining patient preferences for alternative approaches to antithrombotic prophylaxis and studies that examined, in the context of antithrombotic prophylaxis or treatment, how patients value alternative health states and experiences with treatment. We conducted a systematic search and compiled structured summaries of the results. Steps in the process that involved judgment were conducted in duplicate.

Results:  We identified 48 eligible studies. Sixteen dealt with atrial fibrillation, five with VTE, four with stroke or myocardial infarction prophylaxis, six with thrombolysis in acute stroke or myocardial infarction, and 17 with burden of antithrombotic treatment.

Conclusion:  Patient values and preferences regarding thromboprophylaxis treatment appear to be highly variable. Participant responses may depend on their prior experience with the treatments or health outcomes considered as well as on the methods used for preference elicitation. It should be standard for clinical practice guidelines to conduct systematic reviews of patient values and preferences in the specific content area.

Guideline panels require the best evidence regarding patient values and preferences in making trade-offs between desirable and undesirable consequences of alternative management strategies.1 We define “values and preferences” as a broad term that includes patient perspectives, beliefs, expectations, and goals for their health and life, including the process that patients go through in weighing the potential benefits, harms, costs, and burdens associated with different treatment or disease management options.2 Recommendations regarding antithrombotic therapy typically involve trade-offs between decreased risk of thrombosis vs increased bleeding risk and burden of treatment. To inform recommendations of the Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines, we conducted a systematic review to determine what is known regarding patient values and preferences for and experiences with antithrombotic therapy (including prophylaxis and treatment).

1.1 Eligibility Criteria

We included studies that enrolled individuals potentially at risk of or having direct experience with conditions for which antithrombotic therapy may be indicated. We specifically included:

  • Studies that examined patient preferences for antithrombotic therapy vs no or alternative antithrombotic therapy, which includes receiving both treatment for thromboembolic disease and prophylaxis as defined previously

  • Studies that examined in the context of consideration of antithrombotic therapy how patients value alternative health states and experiences with treatment

  • Studies that examined choices patients make when presented with decision aids for management options regarding antithrombotic therapy

We excluded studies of proxy decision makers and health-care professionals and studies that were not available in English.

1.2 Search Strategy

We developed electronic search strategies with the help of a health-care librarian (N. B.). We searched Medline, Embase, Psychinfo, HealthStar, CINAHL, CENTRAL, and International Pharmaceuticals Abstracts between August and September 2009, starting with the dates of inception of each database.

We also searched the gray literature, including the International Society for Quality of Life conference abstracts (2000-2008), the Society for Medical Decision Making conference abstracts available online (2001, 2004-2008), PapersFirst, and Dissertations and Theses International. Finally, we reviewed reference lists of all eligible studies.

1.3 Selection of Studies

Two reviewers independently screened for eligibility the titles and abstracts of identified articles. S. MacLean served as the first reviewer, whereas six authors split the task of the second reviewer (S. McLeod, S. Mulla, M. J., E. A. A., P. O. V., and S. E.); only one reviewer screened conference abstracts. We conducted calibration exercises to ensure consistency among reviewers. We retrieved the full texts of articles judged as potentially eligible by at least one reviewer. Two reviewers then independently screened all full texts for eligibility using a standardized form with explicit inclusion and exclusion criteria. Reviewers resolved their disagreements by discussion or by consulting a third reviewer (G. H. G.).

1.4 Data Abstraction

In pairs, reviewers independently abstracted the following data from each article using a standardized data abstraction form: study design; population and health conditions of interest; antithrombotic medication; outcomes assessed; results; and methodologic characteristics of the study, including systematic biases and potential limitations.

1.5 Data Analysis

We planned to conduct a meta-analysis if the treatment outcomes considered were comparable. The variability in methods and the ways outcomes were measured and presented made the generation of pooled estimates impossible. We present the results in narrative and tabular form, stratified by the health condition.

2.1 Included Studies

Of 48 studies selected for inclusion, 16 focused on patients with atrial fibrillation,318 five on patients with VTE,1923 four on stroke or myocardial infarction prophylaxis,2427 six on thrombolysis in acute stroke or myocardial infarction,2833 and 17 on the burden of antithrombotic treatment.3450 Strategies used to elicit patient preferences include visual analog scales25,37,42,50; standard gamble17,22,23,30; time trade-off68,15,1921; probability trade-off technique3,4,9,12,25,26; decision aids10,13,14,18,31; the presentation of hypothetical scenarios in which participants are asked to make a treatment decision5,11,16,24,32,33; and methods used to elicit information about treatment burden, such as interviews and surveys.27,29,3541,4350

Of the 48 included studies, 12 provided health state utilities or health state valuations obtained from participants with regard to both long-term and short-term outcomes related to thrombolysis and prophylaxis treatments68,15,17,1923,25,30 (Table 1). Health state utilities typically are assessed on a scale of 0 to 1, with 0 being equivalent or worse health, and 1 being optimal health. A patient or participant’s utility value reflects his or her opinions or attitudes toward a given health state or outcome. Disutility refers to the burden or negative outcomes associated with a particular health state.

Table Graphic Jump Location
Table 1 —[Section 2.1] Participant Health State Utility Valuations

G = Pgeneral practitioner; HSU = health state utility; IQR = interquartile range; MI = myocardial infarction; PPS = postphlebitic syndrome; PTS = postthrombotic syndrome; SG = standard gamble; TTO = time trade-off; VAS = visual analog scale; VKA = vitamin K antagonist.

a 

Rescaled from 0-100-point rating. Alonso-Coello P, Montori VM, Diaz MG, et al, unpublished data, 2008.

b 

Assumed normal distribution (mean = median); 95% CI/3.92 = SD.

c 

IQR/1.349 = SD.

d 

Given that the sample size for Gage et al8 is , 25 (n = 14), we cannot transform the data to SD.

e 

Range × 0.25 = SD.

2.2 Overall Findings

Although there were exceptions,13,14 participants across the studies tended to place a higher disutility on stroke than GI bleed3,4,25 and much greater disutility on stroke than treatment burden.68 However, there was little consistency in health state utilities and preferences for treatment choices both within and across studies. We outline the range of participant preferences in categories of presentation. Unless otherwise indicated, the term “stroke” refers to the net of nonfatal hemorrhagic and nonfatal thrombotic stroke. The term “bleed” refers to nonfatal GI bleeding.

3.1 Summary of Findings

Three studies reported compelling findings of a higher disutility associated with stroke than with bleed. Alonso-Coello et al3 found that 19 of 96 participants (20%) were willing to accept > 35 additional bleeds on warfarin for 3% absolute risk reduction of stroke. For this 20%, the disutility associated with one stroke was equal to the disutility associated with 11.6 bleeding episodes. The median threshold that patient-participants were willing to accept was 10 bleeds for a 3% reduction in stroke (range, 1-100). Similarly, Devereaux and colleagues4 found that 57% of participants were willing to accept 22 additional bleeds to achieve a stroke reduction of 8% (disutility of one stroke equal to 2.8 bleeds). The remaining 43% of participants varied considerably in the number of additional instances of bleed that they were willing to accept. The mean number of bleeds that all participants were willing to accept to achieve this 8% stroke reduction was 17.4.

Man-Son-Hing12 found that given a bleeding risk of 3% over 2 years, the mean stroke reduction that participants required to accept warfarin was 1.65% over the same time period. Fifty-two percent of participants would accept warfarin for an absolute decrease in stroke risk by 1% over 2 years. The low treatment threshold in this study may be partly due to the fact that 90% of participants had been taking warfarin at the time of the first interview, and all participants had previously been prescribed warfarin.

A number of studies reported a stroke-to-bleed preference ratio of < 2.11,13,14 Patients enrolled in these studies appeared to place a considerably higher value on avoiding bleeding relative to avoiding stroke than did patients in most other studies.13

Another study conducted by Man-Son-Hing and colleagues14 randomized 199 participants to a qualitative vs quantitative version of a decision aid trial. None of the participants had atrial fibrillation, 31% had experienced aspirin treatment, and 6% had experienced warfarin treatment. The investigators categorized participants in both groups as low risk or moderate risk for stroke. In the low-risk group, participants were told that warfarin, compared with aspirin, resulted in a 1% reduction in stroke and a 2.5% increase in bleeds. The majority (69%) of participants in this group chose aspirin; 4% chose warfarin, 14% chose no medication, and 13% were unable to make a treatment decision. The majority who chose aspirin placed an implicit value on stroke reduction of < 2.5 times the disutility of bleeding.

In the moderate-risk group, participants were told that warfarin, compared with aspirin, results in a 3% absolute risk reduction in stroke and a 2.5% increase in bleeds. The majority (58.1%) of participants in this group chose aspirin; 11% opted for no treatment, 12% chose warfarin, and 18.4% were unable to make a treatment decision. The majority who chose aspirin placed a value on stroke reduction of < 0.83 times the value placed on bleeding.

Holbrook and colleagues11 presented participants with information about atrial fibrillation using an audiotape and booklet. In a typical scenario, warfarin provided a 6% absolute risk reduction in stroke (9%-3%) and a 4% absolute risk increase in bleed (2%-6%) compared with no treatment. In this scenario, 65% of participants chose warfarin, and 35% chose no treatment. For the 65% choosing warfarin, the disutility associated with one stroke was at least 1.5 times greater than the disutility associated with a major bleed.

There are several potential explanations for the variability in results among studies. The first concerns participants’ previous experience with antithrombotic treatment. The low treatment threshold in the 1996 study by Man-Son-Hing12 (> 50% had a disutility of stroke vs bleeding > 3:1) may be partly due to the fact that 90% of the participants had been taking warfarin at the time of the first interview and that all participants had previously been prescribed warfarin. In contrast, participants in the 1999 study by Man-Son-Hing et al13 reported a higher disutility with bleeds. The patients in this study had chosen at enrollment in Stroke Prevention in Atrial Fibrillation III (SPAF) 2 years earlier to receive aspirin prophylaxis alone. Most, if not all, of the participants had not experienced a stroke during the subsequent 2 years. Participants may have believed that whatever the general risk of stroke while taking aspirin, their personal risk was lower (and, at least to some extent, they might have been correct in this deduction)51 (Table 2).

Table Graphic Jump Location
Table 2 —[Section 3.0] Atrial Fibrillation Studies
a 

Alonso-Coello P, Montori VM, Diaz MG, et al, unpublished data, 2008.

Some studies do not provide enough information to enable us to make reliable inferences regarding patient preferences. For example, Fuller et al5 did not report what information they provided patients about the mortality associated with stroke and bleed (presumably, their scenarios referred to nonfatal stroke and bleed), nor did they indicate whether they provided any information about the consequences of a thrombotic stroke or intracranial bleed. These omissions make the results difficult to interpret. To the extent, however, that patients assumed that the functional consequences of a thrombotic stroke and an intracranial bleed are similar, the results of this study suggest that many patients place a higher value on avoiding an adverse event that occurs as a consequence of treatment vs avoiding an event with the same functional consequences that occurs as a consequence of not using that treatment. Table 25154 provides a summary of all studies that considered atrial fibrillation.

4.1 Summary of Findings

These studies illustrate significant variability in elicited patient values and preferences regarding thrombosis prophylaxis and treatment. Locadia et al20 described extremely large between-patient variability with regard to participant willingness to accept warfarin treatment at varying thresholds of recurrent DVT. In another study by Locadia et al,21 the authors concluded that preferences stated in the form of health state utilities varied significantly across the three methods (Table 3).

Table Graphic Jump Location
Table 3 —[Section 4.0] VTE/DVT Prophylaxis and Treatment Studies

D = dalteparin. See Table 1 and 2 legends for expansion of other abbreviations.

5.1 Summary of Findings

A study by O’Meara et al23 found that no participant values and preferences were consistent with taking streptokinase, which differs from the findings of Lenert and Soetikno22 where the majority of participant preferences were consistent with use of streptokinase. Lenert and Soetikno22 explained these differences in results by arguing that their participants were better educated about the risks and benefits of DVT and its treatment, given that participants were presented with video and audio descriptions. O’Meara et al23 provided only written material to participants; thus, their participants may have lacked a full understanding of the outcomes associated with antithrombotic treatment. Another factor potentially affecting results is that participants in the Lenert and Soetikno22 study were younger and, thus, potentially less risk averse than the participants in the O’Meara et al23 study (Table 4).

Table Graphic Jump Location
Table 4 —[Section 5.0] VTE/DVT Thrombolysis Studies

H = heparin; SK = streptokinase. See Table 1 and 2 legends for expansion of other abbreviations.

6.1 Summary of Findings

The results of each of these studies illustrate how design features and participant characteristics may affect reported values and preferences. For example, in the 2001 study by Man-Son-Hing et al,26 enrollees in the Aspirin for Primary Prevention in the Low-risk Elderly (APPLE) pilot study would accept aspirin to gain a significantly smaller reduction in first-time stroke risk compared with those who did not enroll. This finding may indicate that individuals who enroll in trials may have higher acceptance for treatment than those who do not.

Results from a 2000 study by Man-Son-Hing et al25 help to defend the claim that differing methods for preference and health state utility valuations may affect reported preferences. Of the 42 participants who rated preferences using two methods, 43% reported that they would base their decision on the results of the probability trade-off technique, and 17% would base their decision on the decision analysis. The remaining 40% had no preference between the two.

Results from a study by Bergus et al24 suggest that methods used to relay information about risks and benefits of therapy may significantly affect their reported preferences. Participants who received treatment benefits following risks were more likely to accept aspirin than those who received information in the opposite order. This may relate to the concept of loss aversion, which refers to the tendency for individuals to prefer avoiding loss in favor of gaining benefits.55 The results of a study by Montori et al2 illustrate that similar to other studies, previous experience with a given treatment affects the valuation of the outcomes or risks associated with that treatment (Table 5).

Table Graphic Jump Location
Table 5 —[Section 6.0] Stroke and MI Prophylaxis Studies

See Table 1 and 2 legends for expansion of abbreviations.

7.1 Summary of Findings

Results from Slot and Berge30 indicate that compared with individuals who have not experienced a given health event, those who have may associate a higher utility to that event . This factor may be important to consider when eliciting health state valuations for outcomes associated with antithrombotic treatment. These studies also illustrate that other factors such as age, sex, and living situation affect willingness to accept or reject treatment options (Table 6).

Table Graphic Jump Location
Table 6 —[Section 7.0] Stroke Thrombolysis Studies

tPA = tissue plasminogen activator. See Table 1 and 2 legends for expansion of other abbreviations.

8.1 Summary of Findings

One could infer from the results of Heyland et al31 that many patients are extremely stroke averse (valuing avoiding stroke to a considerably greater extent than avoiding death). More likely, the results suggest that patients place a higher value on avoiding treatment-induced adverse (eg, hemorrhagic stroke) events than avoiding events prevented as a result of treatment. This latter interpretation is consistent with results from Fuller et al,5 who examined the relative aversion to thrombotic and hemorrhagic stroke and found that patients placed a greater value on avoiding treatment-induced strokes than on avoiding strokes that treatment could prevent. This finding could relate to the concept of loss aversion.55

Stanek et al32 suggested, in contrast with Heyland et al,31 that participants were most concerned with mortality as opposed to stroke. Participants were most often unwilling to accept a higher risk of death in exchange for a reduction in stroke risk. Differences in results may be attributed to participant populations, methods, and outcomes considered. For example, Stanek et al32 used a self-administered questionnaire, whereas Heyland et al31 conducted a face-to-face preference elicitation exercise, with a research assistant guiding participants through the decision aid. Given that in Stanek, under conditions of no cost and 0% risk of mortality, approximately one-third of participants chose tissue plasminogen activator (which is associated with higher stroke risk), it is possible that at least some of these participants lacked a proper understanding of the risks and outcomes associated with each treatment. Heyland elicited preferences from participants considered at risk for myocardial infarction, whereas Stanek surveyed inpatients undergoing diagnostic coronary angiography. Finally, Stanek considered only hemorrhagic stroke, whereas Heyland included both hemorrhagic stroke and myocardial infarction (Table 7).

Table Graphic Jump Location
Table 7 —[Section 8.0] MI Thrombolysis Studies
9.1 Summary of Findings

Warfarin is, for most patients, associated with relatively limited impact on quality of life and the ability to carry out daily activities. Although some patients report anxiety or worry over the risks that they incur while taking warfarin therapy,3537,40,41 they generally are satisfied with this treatment.39,46 Other elements of burden that patients report include dietary modifications and the inconvenience associated with frequent blood monitoring. Duration of warfarin therapy was positively attributed to satisfaction with treatment.38,40 Duration of low-molecular-weight heparin or unfractionated heparin therapy was associated with increased patient quality of life.50

Injection treatments and compression devices are well tolerated by most patients. However, when given the choice, most patients would prefer injection treatment because of the discomfort associated with compression treatment44 (Table 8).

Table Graphic Jump Location
Table 8 —[Section 9.0] Studies Reporting Treatment Burden and Quality of Life With Antithrombotic Interventions

EPC = external pneumatic compression; INR = international normalized ratio; LMWH = low-molecular-weight heparin; MOS-SF-20 = Medical Outcome Study Short Form 20; PACT-Q2 = Perception of Anticoagulant Therapy Questionnaire 2; QOL = quality of life; SF-36 = Medical Outcome Study Short Form 36; UFH = unfractionated heparin. See Table 1 and 2 legends for expansion of other abbreviations.

There are a number of limitations associated with the included studies. Only three studies reported comprehension screening of potential participants,3,4,12 and two used only the data from participants with consistent results.6,31 Le Sage and colleagues48 had research assistants walk through the survey with participants to ensure that the participants understood all the questions. It is possible that for those studies that did not pretest for comprehension, preferences elicited using methods such as time trade-off, probability trade-off, and standard gamble may have been compromised because of a lack of participant understanding. For example, Thomson et al18 designed their study as a three-arm trial, one arm of which elicited patient preferences through the standard gamble method. After realizing that participants were having difficulty understanding the standard gamble, they dropped that arm of the study.

Studies were also inconsistent in the descriptions of health states presented to participants in terms of both the number and the type of health states considered (eg, major bleed, major side effects, stroke). For example, Protheroe et al15 grouped major and minor side effects together (not typical), whereas other studies did not consider minor side effects at all. As well, when describing the outcomes associated with stroke, some authors centered their descriptions on the physical effects,30 whereas others considered additional aspects, such as the likelihood of becoming depressed or losing the ability to comprehend language.21 Given the complexity of the treatment decision in this context, we do not consider studies to be biased if they neglected to consider rare or minor outcomes because including these may overwhelm participants and affect the validity of the outcomes.

The methodologic quality of the included studies is concerning, and most studies are compromised by some form of selection bias. For example, whether patients had previously experienced the condition or health events under consideration may have influenced their preference. Slot and Berge30 found that those participants who had previously experienced a stroke tended to place a lower disutility on stroke than did those who had not experienced stroke events. Ideally, investigators would have recruited individuals recently given a diagnosis of the condition under study and who had not made a treatment decision. None of the included studies did.

In addition, participants’ prior associations with the treatments under study may have affected willingness to accept specific treatment options. For example, Holbrook et al10 found that 36% of participant treatment preferences changed once given the treatment names (placebo, aspirin, and warfarin); the majority of these switches were to aspirin.

We have carried out a systematic review of studies reporting patient values and preferences with regard to antithrombotic treatment. The results obtained through this review provide direction for guideline developers to base recommendations on patient values. In particular, this review highlights the apparently large variability in participant health state valuations and the factors, other than the impact of alternative management strategies on quantity and quality of life, that influence patient decisions.

A number of factors may explain the large variability in patient preferences both within and across studies. First, whether patients had experienced the treatments under consideration appeared to influence results. Typically, previous exposure with a given treatment was associated with a preference for continuing that same treatment.12,13,45 Cognitive dissonance occurs when participants are inclined to modify their interpretation of information to ensure that it is consistent with their previous decision.56 To reduce cognitive dissonance, participants who had previously been exposed to the treatments under consideration may be inclined to continue their treatment, even in the face of information suggesting that it is not the optimal choice. Patients who do not want to believe that they have been taking the wrong treatment may interpret the evidence presented so that it is consistent with their prior choice.

In addition, and perhaps most importantly, the differing methods used to elicit values and preferences may have resulted in differing apparent treatment preferences and health state valuations. Few studies attempted to determine whether methods such as probability trade-off, decision analysis, and differing methods for obtaining health state utilities would result in different choices. Indeed, in two studies,20,25 investigators found that methods used to elicit preferences significantly affected treatment health state valuations and treatment thresholds.

The relatively small number of studies, their small sample sizes, their methodological limitations, and the large variability in their findings limit the inferences that we can confidently draw. We consider the following conclusions, however, as reasonably robust:

  • 1.

    Values and preferences for antithrombotic treatment and for health states appear to vary appreciably among individuals.

  • 2.

    Heterogeneity of results across studies—often difficult to explain—leaves appreciable uncertainty about average patient values.

Study results suggest the following average values for the health states of interest:

  • 3.

    Although there are troubling inconsistencies across studies, particularly in Man-Son-Hing et al,14 a reasonable trade-off to assume between stroke and bleeds would be a ratio of disutility of net nonfatal stroke (thrombotic or hemorrhagic) to GI bleeds in the range of 2:1 to 3:1.

  • 4.

    There is much less information about the relative disutility of myocardial infarction and bleeds, although it is clear that myocardial infarction has substantially less disutility than major stroke (and more than minor stroke). A reasonable trade-off to assume between myocardial infarction and bleeds would be 1:1 to 2:1.

  • 5.

    The only conclusion that one can make regarding the relative disutility of major bleed vs DVT is that it varies widely among patients.

  • 6.

    Patients are unwilling to accept a small increase in risk of death to avoid the postthrombotic syndrome.5,23

Study results suggest the following preferences for the antithrombotic interventions:

  • 7.

    For most patients, vitamin K antagonist therapy does not have important negative effects on quality of life, although many patients worry about the side effects associated with vitamin K antagonist treatment.

  • 8.

    Patient aversion to warfarin treatment may decrease over time after treatment is initiated.

  • 9.

    Injection treatments are well tolerated.

  • 10.

    Compression stockings are well tolerated but less preferred compared with injection treatments.

The present study has several limitations. Given the large number of abstracts that were selected for review (N = 17,086), it was not feasible to seek out articles that could not be obtained online. Therefore, this study comprises only articles that could be accessed through the electronic library at McMaster University. Eight articles that we deemed potentially relevant were special ordered; two proved eligible. It is possible that we were unable to capture every eligible study in this review, and we expect that authors may come forward with additional studies to be included in an update of this review. Although we attempted to locate unpublished studies by reviewing the gray literature and contacting experts in the field (which did produce two additional articles), this review risks publication bias.57

Our findings have a number of implications for future studies eliciting patient values and preferences. First, investigators should elicit values and preferences from participants who have not previously made the choices under investigation. Although prior experiences may result in a better understanding of the treatment under consideration, it may introduce factors other than preferences for the health states described in their responses (particularly cognitive dissonance). Second, in order to gain a better understanding of whether differing health state descriptions significantly affect health state valuations, future research may test the impact of different descriptions on participant valuations. Ideally, standard descriptions of bleed and stroke outcomes would be developed and applied across studies. Finally, research should ensure that participants understand the preference elicitation exercise and explore factors that bear significantly on patient decisions.

Our findings also have implications for guideline development. The uncertainty and the variability in values and preferences among patients suggest that the present guideline panels should be circumspect in making strong recommendations. Strong recommendations should be restricted to situations in which the desirable consequences of an intervention substantially outweigh the undesirable consequences.

Author contributions: As Topic Editor, Ms MacLean oversaw the development of this article, including the data analysis and findings contained herein

Ms MacLean: served as Topic Editor

Mr Mulla: served as a panelist

Dr Jankowski: served as a panelist

Dr Akl: served as a panelist

Dr Vandvik: served as a panelist

Mr Ebrahim: served as a panelist

Ms McLeod: served as a panelist

Ms Bhatnagar: served as a panelist

Dr Guyatt: served as a panelist

Financial/nonfinancial disclosures: In summary, the authors have reported to CHEST the following conflicts of interest: Dr Guyatt is co-chair of the GRADE Working Group, and Drs Akl and Vandvik are members and prominent contributors to the Grade Working Group. Mss MacLean, McLeod, and Bhatnagar; Messrs Mulla and Ebrahim; and Dr Jankowski have reported that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

Role of sponsors: The sponsors played no role in the development of these guidelines. Sponsoring organizations cannot recommend panelists or topics, nor are they allowed prepublication access to the manuscripts and recommendations. Guideline panel members, including the chair, and members of the Health & Science Policy Committee are blinded to the funding sources. Further details on the Conflict of Interest Policy are available online at http://chestnet.org.

Endorsements: This guideline is endorsed by the American Association for Clinical Chemistry, the American College of Clinical Pharmacy, the American Society of Health-System Pharmacists, the American Society of Hematology, and the International Society of Thrombosis and Hematosis.

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Holbrook A, Labiris R, Goldsmith CH, Ota K, Harb S, Sebaldt RJ. Influence of decision aids on patient preferences for anticoagulant therapy: a randomized trial. CMAJ. 2007;17611:1583-1587. [CrossRef] [PubMed]
 
Holbrook A, Schulman S, Witt DM, et al. Evidence-based management of anticoagulant therapy: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2012;1412suppl:e152S-e184S. [CrossRef] [PubMed]
 
Man-Son-Hing M. The Efficacy of Warfarin for the Prevention of Stroke in Nonvalvular Atrial Fibrillation: Measuring Its Minimal Clinically Important Difference From the Patients’ Perspective[master’s thesis]. 1996; Ottawa, Ontario, Canada University of Ottawa:148-148
 
Man-Son-Hing M, Laupacis A, O’Connor AM, et al; Stroke Prevention in Atrial Fibrillation Investigators Stroke Prevention in Atrial Fibrillation Investigators A patient decision aid regarding antithrombotic therapy for stroke prevention in atrial fibrillation: a randomized controlled trial. JAMA. 1999;2828:737-743. [CrossRef] [PubMed]
 
Man-Son-Hing M, O’Connor AM, Drake E, Biggs J, Hum V, Laupacis A. The effect of qualitative vs. quantitative presentation of probability estimates on patient decision-making: a randomized trial. Health Expect. 2002;53:246-255. [CrossRef] [PubMed]
 
Protheroe J, Fahey T, Montgomery AA, Peters TJ. The impact of patients’ preferences on the treatment of atrial fibrillation: observational study of patient based decision analysis. BMJ. 2000;3207246:1380-1384. [CrossRef] [PubMed]
 
Sudlow M, Thomson R, Kenny RA, Rodgers H. A community survey of patients with atrial fibrillation: associated disabilities and treatment preferences. Br J Gen Pract. 1998;48436:1775-1778. [PubMed]
 
Thomson R, Parkin D, Eccles M, Sudlow M, Robinson A. Decision analysis and guidelines for anticoagulant therapy to prevent stroke in patients with atrial fibrillation. Lancet. 2000;3559208:956-962. [CrossRef] [PubMed]
 
Thomson RG, Eccles MP, Steen IN, et al. A patient decision aid to support shared decision-making on anti-thrombotic treatment of patients with atrial fibrillation: randomised controlled trial. Qual Saf Health Care. 2007;163:216-223. [CrossRef] [PubMed]
 
Dranitsaris G, Stumpo C, Smith R, Bartle W. Extended dalteparin prophylaxis for venous thromboembolic events: cost-utility analysis in patients undergoing major orthopedic surgery. Am J Cardiovasc Drugs. 2009;91:45-58. [CrossRef] [PubMed]
 
Locadia M, Bossuyt PM, Stalmeier PF, et al. Treatment of venous thromboembolism with vitamin K antagonists: patients’ health state valuations and treatment preferences. Thromb Haemost. 2004;926:1336-1341. [PubMed]
 
Locadia M, Stalmeier PF, Oort FJ, Prins MH, Sprangers MA, Bossuyt PM. A comparison of 3 valuation methods for temporary health states in patients treated with oral anticoagulants. Med Decis Making. 2004;246:625-633. [CrossRef] [PubMed]
 
Lenert LA, Soetikno RM. Automated computer interviews to elicit utilities: potential applications in the treatment of deep venous thrombosis. J Am Med Inform Assoc. 1997;41:49-56. [CrossRef] [PubMed]
 
O’Meara JJ III, McNutt RA, Evans AT, Moore SW, Downs SM. A decision analysis of streptokinase plus heparin as compared with heparin alone for deep-vein thrombosis. N Engl J Med. 1994;33026:1864-1869. [CrossRef] [PubMed]
 
Bergus GR, Levin IP, Elstein AS. Presenting risks and benefits to patients. J Gen Intern Med. 2002;178:612-617. [CrossRef] [PubMed]
 
Man-Son-Hing M, Laupacis A, O’Connor AM, Coyle D, Berquist R, McAlister F. Patient preference-based treatment thresholds and recommendations: a comparison of decision-analytic modeling with the probability-tradeoff technique. Med Decis Making. 2000;204:394-403. [CrossRef] [PubMed]
 
Man-Son-Hing M, Hart RG, Berquist R, O’Connor AM, Laupacis A. Differences in treatment preferences between persons who enroll and do not enroll in a clinical trial. Ann R Coll Physicians Surg Can. 2001;345:292-296. [PubMed]
 
Montori VM, Bryant SC, O’Connor AM, Jorgensen NW, Walsh EE, Smith SA. Decisional attributes of patients with diabetes: the aspirin choice. Diabetes Care. 2003;2610:2804-2809. [CrossRef] [PubMed]
 
Kapral MK, Devon J, Winter AL, Wang J, Peters A, Bondy SJ. Gender differences in stroke care decision-making. Med Care. 2006;441:70-80. [CrossRef] [PubMed]
 
Mangset M, Berge E, Førde R, Nessa J, Wyller TB. “Two percent isn’t a lot, but when it comes to death it seems quite a lot anyway”: patients’ perception of risk and willingness to accept risks associated with thrombolytic drug treatment for acute stroke. J Med Ethics. 2009;351:42-46. [CrossRef] [PubMed]
 
Slot KB, Berge E. Thrombolytic treatment for stroke: patient preferences for treatment, information, and involvement. J Stroke Cerebrovasc Dis. 2009;181:17-22. [CrossRef] [PubMed]
 
Heyland DK, Gafni A, Levine MA. Do potential patients prefer tissue plasminogen activator (TPA) over streptokinase (SK)? An evaluation of the risks and benefits of TPA from the patient’s perspective. J Clin Epidemiol. 2000;539:888-894. [CrossRef] [PubMed]
 
Stanek EJ, Cheng JW, Peeples PJ, Simko RJ, Spinler SA. Patient preferences for thrombolytic therapy in acute myocardial infarction. Med Decis Making. 1997;174:464-471. [CrossRef] [PubMed]
 
Tsui W, Pierre K, Massel D. Patient reperfusion preferences in acute myocardial infarction: mortality versus stroke, benefits versus costs, high technology versus drugs. Can J Cardiol. 2005;215:423-431. [PubMed]
 
Anand S, Asumu T. Patient acceptance of a foot pump device used for thromboprophylaxis. Acta Orthop Belg. 2007;733:386-389. [PubMed]
 
Arnsten JH, Gelfand JM, Singer DE. Determinants of compliance with anticoagulation: A case-control study. Am J Med. 1997;1031:11-17. [CrossRef] [PubMed]
 
Barcellona D, Contu P, Sorano GG, Pengo V, Marongiu F. The management of oral anticoagulant therapy: the patient’s point of view. Thromb Haemost. 2000;831:49-53. [PubMed]
 
Davis NJ, Billett HH, Cohen HW, Arnsten JH. Impact of adherence, knowledge, and quality of life on anticoagulation control. Ann Pharmacother. 2005;394:632-636. [CrossRef] [PubMed]
 
Casais P, Meschengieser SS, Sanchez-Luceros A, Lazzari MA. Patients’ perceptions regarding oral anticoagulation therapy and its effect on quality of life. Curr Med Res Opin. 2005;217:1085-1090. [CrossRef] [PubMed]
 
Dantas GC, Thompson BV, Manson JA, Tracy CS, Upshur RE. Patients’ perspectives on taking warfarin: qualitative study in family practice. BMC Fam Pract. 2004;5:15. [CrossRef] [PubMed]
 
Jaffary F, Khan T, Kamali F, Hutchinson M, Wynne HA. The effect of stability of oral anticoagulant therapy upon patient-perceived health status and quality of life. J Am Geriatr Soc. 2003;516:885-887. [CrossRef] [PubMed]
 
Lancaster TR, Singer DE, Sheehan MA, et al; Boston Area Anticoagulation Trial for Atrial Fibrillation Investigators Boston Area Anticoagulation Trial for Atrial Fibrillation Investigators The impact of long-term warfarin therapy on quality of life. Evidence from a randomized trial. Arch Intern Med. 1991;15110:1944-1949. [CrossRef] [PubMed]
 
Locadia M, Sprangers MA, de Haes HC, Büller HR, Prins MH. Quality of life and the duration of treatment with vitamin K antagonists in patients with deep venous thrombosis. Thromb Haemost. 2003;901:101-107. [PubMed]
 
Noble SI, Finlay IG. Is long-term low-molecular-weight heparin acceptable to palliative care patients in the treatment of cancer related venous thromboembolism? A qualitative study. Palliat Med. 2005;193:197-201. [CrossRef] [PubMed]
 
Noble SI, Nelson A, Turner C, Finlay IG. Acceptability of low molecular weight heparin thromboprophylaxis for inpatients receiving palliative care: qualitative study. BMJ. 2006;3327541:577-580. [CrossRef] [PubMed]
 
Maxwell GL, Synan I, Hayes RP, Clarke-Pearson DL. Preference and compliance in postoperative thromboembolism prophylaxis among gynecologic oncology patients. Obstet Gynecol. 2002;1003:451-455. [CrossRef] [PubMed]
 
Samsa G, Matchar DB, Dolor RJ, et al. A new instrument for measuring anticoagulation-related quality of life: development and preliminary validation. Health Qual Life Outcomes. 2004;2:22. [CrossRef] [PubMed]
 
Warwick D, Harrison J, Glew D, Mitchelmore A, Peters TJ, Donovan J. Comparison of the use of a foot pump with the use of low-molecular-weight heparin for the prevention of deep-vein thrombosis after total hip replacement. A prospective, randomized trial. J Bone Joint Surg Am. 1998;808:1158-1166. [PubMed]
 
Le Sage S, McGee M, Emed JD. Knowledge of venous thromboembolism (VTE) prevention among hospitalized patients. J Vasc Nurs. 2008;264:109-117. [CrossRef] [PubMed]
 
Prins MH, Guillemin I, Gilet H, et al. Scoring and psychometric validation of the Perception of Anticoagulant Treatment Questionnaire (PACT-Q). Health Qual Life Outcomes. 2009;7:30. [CrossRef] [PubMed]
 
Koopman MMW, Prandoni P, Piovella F, et al; The Tasman Study Group The Tasman Study Group Treatment of venous thrombosis with intravenous unfractionated heparin administered in the hospital as compared with subcutaneous low-molecular-weight heparin administered at home. N Engl J Med. 1996;33411:682-687. [CrossRef] [PubMed]
 
The SPAF III Writing Committee for the Stroke Prevention in Atrial Fibrillation InvestigatorsThe SPAF III Writing Committee for the Stroke Prevention in Atrial Fibrillation Investigators Patients with nonvalvular atrial fibrillation at low risk of stroke during treatment with aspirin: Stroke Prevention in Atrial Fibrillation III Study. JAMA. 1998;27916:1273-1277. [CrossRef] [PubMed]
 
Man-Son-Hing M, Laupacis A, O’Connor A, et al; Warfarin for atrial fibrillation Warfarin for atrial fibrillation The patient’s perspective. Arch Intern Med. 1996;15616:1841-1848. [CrossRef] [PubMed]
 
Man-Son-Hing M, Laupacis A, O’Connor AM, et al. A patient decision aid regarding antithrombotic therapy for stroke prevention in atrial fibrillation: a randomized controlled trial. JAMA. 1999;2828:737-743. [CrossRef] [PubMed]
 
Man-Son-Hing M, Laupacis A. Balancing the risks of stroke and upper gastrointestinal tract bleeding in older patients with atrial fibrillation. Arch Intern Med. 2002;1625:541-550. [CrossRef] [PubMed]
 
Tversky A, Kahneman D. Loss aversion in riskless choice: a reference-dependent model. Q J Econ. 1991;1064:1039-1061. [CrossRef]
 
Draycott S, Dabbs A. Cognitive dissonance. 1: An overview of the literature and its integration into theory and practice in clinical psychology. Br J Clin Psychol. 1998;37Pt 3:341-353. [CrossRef] [PubMed]
 
Khan KS, Kunz R, Kleijnen J, Antes G. Five steps to conducting a systematic review. J R Soc Med. 2003;963:118-121. [CrossRef] [PubMed]
 

Figures

Tables

Table Graphic Jump Location
Table 1 —[Section 2.1] Participant Health State Utility Valuations

G = Pgeneral practitioner; HSU = health state utility; IQR = interquartile range; MI = myocardial infarction; PPS = postphlebitic syndrome; PTS = postthrombotic syndrome; SG = standard gamble; TTO = time trade-off; VAS = visual analog scale; VKA = vitamin K antagonist.

a 

Rescaled from 0-100-point rating. Alonso-Coello P, Montori VM, Diaz MG, et al, unpublished data, 2008.

b 

Assumed normal distribution (mean = median); 95% CI/3.92 = SD.

c 

IQR/1.349 = SD.

d 

Given that the sample size for Gage et al8 is , 25 (n = 14), we cannot transform the data to SD.

e 

Range × 0.25 = SD.

Table Graphic Jump Location
Table 2 —[Section 3.0] Atrial Fibrillation Studies
a 

Alonso-Coello P, Montori VM, Diaz MG, et al, unpublished data, 2008.

Table Graphic Jump Location
Table 3 —[Section 4.0] VTE/DVT Prophylaxis and Treatment Studies

D = dalteparin. See Table 1 and 2 legends for expansion of other abbreviations.

Table Graphic Jump Location
Table 4 —[Section 5.0] VTE/DVT Thrombolysis Studies

H = heparin; SK = streptokinase. See Table 1 and 2 legends for expansion of other abbreviations.

Table Graphic Jump Location
Table 5 —[Section 6.0] Stroke and MI Prophylaxis Studies

See Table 1 and 2 legends for expansion of abbreviations.

Table Graphic Jump Location
Table 6 —[Section 7.0] Stroke Thrombolysis Studies

tPA = tissue plasminogen activator. See Table 1 and 2 legends for expansion of other abbreviations.

Table Graphic Jump Location
Table 7 —[Section 8.0] MI Thrombolysis Studies
Table Graphic Jump Location
Table 8 —[Section 9.0] Studies Reporting Treatment Burden and Quality of Life With Antithrombotic Interventions

EPC = external pneumatic compression; INR = international normalized ratio; LMWH = low-molecular-weight heparin; MOS-SF-20 = Medical Outcome Study Short Form 20; PACT-Q2 = Perception of Anticoagulant Therapy Questionnaire 2; QOL = quality of life; SF-36 = Medical Outcome Study Short Form 36; UFH = unfractionated heparin. See Table 1 and 2 legends for expansion of other abbreviations.

References

Oxman AD, Schünemann HJ, Fretheim A. Improving the use of research evidence in guideline development: 10. Integrating values and consumer involvement. Health Res Policy Syst. 2006;4:28. [CrossRef] [PubMed]
 
Montori V, Devereaux P, Straus S, et al;Guyatt G, Drummond R, Meade MO, Cook D. Advanced topics in moving from evidence to action: decision making and the patient. Chapter 22.2. Users’ Guides to the Medical Literature: A Manual for Evidence-Based Clinical Practice. 2008; New York, NY American Medical Association
 
Alonso-Coello P, Montori VM, Solà I, et al. Values and preferences in oral anticoagulation in patients with atrial fibrillation, physicians’ and patients’ perspectives: protocol for a two-phase study. BMC Health Serv Res. 2008;8:21. [CrossRef] [PubMed]
 
Devereaux PJ, Anderson DR, Gardner MJ, et al. Differences between perspectives of physicians and patients on anticoagulation in patients with atrial fibrillation: observational study. BMJ. 2001;3237323:1218-1222. [CrossRef] [PubMed]
 
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;336:608-611. [CrossRef] [PubMed]
 
Gage BF, Cardinalli AB, Albers GW, Owens DK. Cost-effectiveness of warfarin and aspirin for prophylaxis of stroke in patients with nonvalvular atrial fibrillation. JAMA. 1995;27423:1839-1845. [CrossRef] [PubMed]
 
Gage BF, Cardinalli AB, Owens DK. The effect of stroke and stroke prophylaxis with aspirin or warfarin on quality of life. Arch Intern Med. 1996;15616:1829-1836. [CrossRef] [PubMed]
 
Gage BF, Cardinalli AB, Owens DK. Cost-effectiveness of preference-based antithrombotic therapy for patients with nonvalvular atrial fibrillation. Stroke. 1998;296:1083-1091. [CrossRef] [PubMed]
 
Howitt A, Armstrong D. Implementing evidence based medicine in general practice: audit and qualitative study of antithrombotic treatment for atrial fibrillation. BMJ. 1999;3187194:1324-1327. [CrossRef] [PubMed]
 
Holbrook A, Labiris R, Goldsmith CH, Ota K, Harb S, Sebaldt RJ. Influence of decision aids on patient preferences for anticoagulant therapy: a randomized trial. CMAJ. 2007;17611:1583-1587. [CrossRef] [PubMed]
 
Holbrook A, Schulman S, Witt DM, et al. Evidence-based management of anticoagulant therapy: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2012;1412suppl:e152S-e184S. [CrossRef] [PubMed]
 
Man-Son-Hing M. The Efficacy of Warfarin for the Prevention of Stroke in Nonvalvular Atrial Fibrillation: Measuring Its Minimal Clinically Important Difference From the Patients’ Perspective[master’s thesis]. 1996; Ottawa, Ontario, Canada University of Ottawa:148-148
 
Man-Son-Hing M, Laupacis A, O’Connor AM, et al; Stroke Prevention in Atrial Fibrillation Investigators Stroke Prevention in Atrial Fibrillation Investigators A patient decision aid regarding antithrombotic therapy for stroke prevention in atrial fibrillation: a randomized controlled trial. JAMA. 1999;2828:737-743. [CrossRef] [PubMed]
 
Man-Son-Hing M, O’Connor AM, Drake E, Biggs J, Hum V, Laupacis A. The effect of qualitative vs. quantitative presentation of probability estimates on patient decision-making: a randomized trial. Health Expect. 2002;53:246-255. [CrossRef] [PubMed]
 
Protheroe J, Fahey T, Montgomery AA, Peters TJ. The impact of patients’ preferences on the treatment of atrial fibrillation: observational study of patient based decision analysis. BMJ. 2000;3207246:1380-1384. [CrossRef] [PubMed]
 
Sudlow M, Thomson R, Kenny RA, Rodgers H. A community survey of patients with atrial fibrillation: associated disabilities and treatment preferences. Br J Gen Pract. 1998;48436:1775-1778. [PubMed]
 
Thomson R, Parkin D, Eccles M, Sudlow M, Robinson A. Decision analysis and guidelines for anticoagulant therapy to prevent stroke in patients with atrial fibrillation. Lancet. 2000;3559208:956-962. [CrossRef] [PubMed]
 
Thomson RG, Eccles MP, Steen IN, et al. A patient decision aid to support shared decision-making on anti-thrombotic treatment of patients with atrial fibrillation: randomised controlled trial. Qual Saf Health Care. 2007;163:216-223. [CrossRef] [PubMed]
 
Dranitsaris G, Stumpo C, Smith R, Bartle W. Extended dalteparin prophylaxis for venous thromboembolic events: cost-utility analysis in patients undergoing major orthopedic surgery. Am J Cardiovasc Drugs. 2009;91:45-58. [CrossRef] [PubMed]
 
Locadia M, Bossuyt PM, Stalmeier PF, et al. Treatment of venous thromboembolism with vitamin K antagonists: patients’ health state valuations and treatment preferences. Thromb Haemost. 2004;926:1336-1341. [PubMed]
 
Locadia M, Stalmeier PF, Oort FJ, Prins MH, Sprangers MA, Bossuyt PM. A comparison of 3 valuation methods for temporary health states in patients treated with oral anticoagulants. Med Decis Making. 2004;246:625-633. [CrossRef] [PubMed]
 
Lenert LA, Soetikno RM. Automated computer interviews to elicit utilities: potential applications in the treatment of deep venous thrombosis. J Am Med Inform Assoc. 1997;41:49-56. [CrossRef] [PubMed]
 
O’Meara JJ III, McNutt RA, Evans AT, Moore SW, Downs SM. A decision analysis of streptokinase plus heparin as compared with heparin alone for deep-vein thrombosis. N Engl J Med. 1994;33026:1864-1869. [CrossRef] [PubMed]
 
Bergus GR, Levin IP, Elstein AS. Presenting risks and benefits to patients. J Gen Intern Med. 2002;178:612-617. [CrossRef] [PubMed]
 
Man-Son-Hing M, Laupacis A, O’Connor AM, Coyle D, Berquist R, McAlister F. Patient preference-based treatment thresholds and recommendations: a comparison of decision-analytic modeling with the probability-tradeoff technique. Med Decis Making. 2000;204:394-403. [CrossRef] [PubMed]
 
Man-Son-Hing M, Hart RG, Berquist R, O’Connor AM, Laupacis A. Differences in treatment preferences between persons who enroll and do not enroll in a clinical trial. Ann R Coll Physicians Surg Can. 2001;345:292-296. [PubMed]
 
Montori VM, Bryant SC, O’Connor AM, Jorgensen NW, Walsh EE, Smith SA. Decisional attributes of patients with diabetes: the aspirin choice. Diabetes Care. 2003;2610:2804-2809. [CrossRef] [PubMed]
 
Kapral MK, Devon J, Winter AL, Wang J, Peters A, Bondy SJ. Gender differences in stroke care decision-making. Med Care. 2006;441:70-80. [CrossRef] [PubMed]
 
Mangset M, Berge E, Førde R, Nessa J, Wyller TB. “Two percent isn’t a lot, but when it comes to death it seems quite a lot anyway”: patients’ perception of risk and willingness to accept risks associated with thrombolytic drug treatment for acute stroke. J Med Ethics. 2009;351:42-46. [CrossRef] [PubMed]
 
Slot KB, Berge E. Thrombolytic treatment for stroke: patient preferences for treatment, information, and involvement. J Stroke Cerebrovasc Dis. 2009;181:17-22. [CrossRef] [PubMed]
 
Heyland DK, Gafni A, Levine MA. Do potential patients prefer tissue plasminogen activator (TPA) over streptokinase (SK)? An evaluation of the risks and benefits of TPA from the patient’s perspective. J Clin Epidemiol. 2000;539:888-894. [CrossRef] [PubMed]
 
Stanek EJ, Cheng JW, Peeples PJ, Simko RJ, Spinler SA. Patient preferences for thrombolytic therapy in acute myocardial infarction. Med Decis Making. 1997;174:464-471. [CrossRef] [PubMed]
 
Tsui W, Pierre K, Massel D. Patient reperfusion preferences in acute myocardial infarction: mortality versus stroke, benefits versus costs, high technology versus drugs. Can J Cardiol. 2005;215:423-431. [PubMed]
 
Anand S, Asumu T. Patient acceptance of a foot pump device used for thromboprophylaxis. Acta Orthop Belg. 2007;733:386-389. [PubMed]
 
Arnsten JH, Gelfand JM, Singer DE. Determinants of compliance with anticoagulation: A case-control study. Am J Med. 1997;1031:11-17. [CrossRef] [PubMed]
 
Barcellona D, Contu P, Sorano GG, Pengo V, Marongiu F. The management of oral anticoagulant therapy: the patient’s point of view. Thromb Haemost. 2000;831:49-53. [PubMed]
 
Davis NJ, Billett HH, Cohen HW, Arnsten JH. Impact of adherence, knowledge, and quality of life on anticoagulation control. Ann Pharmacother. 2005;394:632-636. [CrossRef] [PubMed]
 
Casais P, Meschengieser SS, Sanchez-Luceros A, Lazzari MA. Patients’ perceptions regarding oral anticoagulation therapy and its effect on quality of life. Curr Med Res Opin. 2005;217:1085-1090. [CrossRef] [PubMed]
 
Dantas GC, Thompson BV, Manson JA, Tracy CS, Upshur RE. Patients’ perspectives on taking warfarin: qualitative study in family practice. BMC Fam Pract. 2004;5:15. [CrossRef] [PubMed]
 
Jaffary F, Khan T, Kamali F, Hutchinson M, Wynne HA. The effect of stability of oral anticoagulant therapy upon patient-perceived health status and quality of life. J Am Geriatr Soc. 2003;516:885-887. [CrossRef] [PubMed]
 
Lancaster TR, Singer DE, Sheehan MA, et al; Boston Area Anticoagulation Trial for Atrial Fibrillation Investigators Boston Area Anticoagulation Trial for Atrial Fibrillation Investigators The impact of long-term warfarin therapy on quality of life. Evidence from a randomized trial. Arch Intern Med. 1991;15110:1944-1949. [CrossRef] [PubMed]
 
Locadia M, Sprangers MA, de Haes HC, Büller HR, Prins MH. Quality of life and the duration of treatment with vitamin K antagonists in patients with deep venous thrombosis. Thromb Haemost. 2003;901:101-107. [PubMed]
 
Noble SI, Finlay IG. Is long-term low-molecular-weight heparin acceptable to palliative care patients in the treatment of cancer related venous thromboembolism? A qualitative study. Palliat Med. 2005;193:197-201. [CrossRef] [PubMed]
 
Noble SI, Nelson A, Turner C, Finlay IG. Acceptability of low molecular weight heparin thromboprophylaxis for inpatients receiving palliative care: qualitative study. BMJ. 2006;3327541:577-580. [CrossRef] [PubMed]
 
Maxwell GL, Synan I, Hayes RP, Clarke-Pearson DL. Preference and compliance in postoperative thromboembolism prophylaxis among gynecologic oncology patients. Obstet Gynecol. 2002;1003:451-455. [CrossRef] [PubMed]
 
Samsa G, Matchar DB, Dolor RJ, et al. A new instrument for measuring anticoagulation-related quality of life: development and preliminary validation. Health Qual Life Outcomes. 2004;2:22. [CrossRef] [PubMed]
 
Warwick D, Harrison J, Glew D, Mitchelmore A, Peters TJ, Donovan J. Comparison of the use of a foot pump with the use of low-molecular-weight heparin for the prevention of deep-vein thrombosis after total hip replacement. A prospective, randomized trial. J Bone Joint Surg Am. 1998;808:1158-1166. [PubMed]
 
Le Sage S, McGee M, Emed JD. Knowledge of venous thromboembolism (VTE) prevention among hospitalized patients. J Vasc Nurs. 2008;264:109-117. [CrossRef] [PubMed]
 
Prins MH, Guillemin I, Gilet H, et al. Scoring and psychometric validation of the Perception of Anticoagulant Treatment Questionnaire (PACT-Q). Health Qual Life Outcomes. 2009;7:30. [CrossRef] [PubMed]
 
Koopman MMW, Prandoni P, Piovella F, et al; The Tasman Study Group The Tasman Study Group Treatment of venous thrombosis with intravenous unfractionated heparin administered in the hospital as compared with subcutaneous low-molecular-weight heparin administered at home. N Engl J Med. 1996;33411:682-687. [CrossRef] [PubMed]
 
The SPAF III Writing Committee for the Stroke Prevention in Atrial Fibrillation InvestigatorsThe SPAF III Writing Committee for the Stroke Prevention in Atrial Fibrillation Investigators Patients with nonvalvular atrial fibrillation at low risk of stroke during treatment with aspirin: Stroke Prevention in Atrial Fibrillation III Study. JAMA. 1998;27916:1273-1277. [CrossRef] [PubMed]
 
Man-Son-Hing M, Laupacis A, O’Connor A, et al; Warfarin for atrial fibrillation Warfarin for atrial fibrillation The patient’s perspective. Arch Intern Med. 1996;15616:1841-1848. [CrossRef] [PubMed]
 
Man-Son-Hing M, Laupacis A, O’Connor AM, et al. A patient decision aid regarding antithrombotic therapy for stroke prevention in atrial fibrillation: a randomized controlled trial. JAMA. 1999;2828:737-743. [CrossRef] [PubMed]
 
Man-Son-Hing M, Laupacis A. Balancing the risks of stroke and upper gastrointestinal tract bleeding in older patients with atrial fibrillation. Arch Intern Med. 2002;1625:541-550. [CrossRef] [PubMed]
 
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