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Self-management of oral anticoagulation
ARTICLE IN PRESS Evidence-Based Healthcare & Public Health (2005) 9, 334–340
www.elsevier.com/locate/ebhph
SYSTEMATIC REVIEW
Self-management of oral anticoagulation Bazian Ltd London, UK
Key points
Many people need long-term anticoagulation treatment to reduce their risk of thromboembolism. The dose of anticoagulant drug required varies unpredictably between individuals and over time. Poor anticoagulation control leads to either inadequate protection against thromboembolism or increased risk of life-threatening bleeding. The degree of anticoagulation needs to be regularly monitored, and the dosage of anticoagulant changed if necessary. Individuals managing their own anticoagulation is feasible, can be more accurate than management by doctors and is acceptable to patients. There remain uncertainties about patient selection and cost-effectiveness. The evidence on quality of life and cost is limited. However, the available evidence suggests self-management is likely to improve quality of life, but may cost more than management by doctors. Difficulties with self-management techniques, lack of confidence in ability to perform self-management, and preference for management by doctors were reported by people withdrawing from the studies, so self-management is not suitable for all people needing long-term anticoagulation.
drugs to reduce their risk, but the dose required varies unpredictably between individuals and over time. Too high a dose leads to a risk of lifethreatening bleeding, while too low a dose will not adequately treat the underlying condition. Therefore, the degree of anticoagulation (expressed as the international normalised ratio; INR), needs monitoring, and appropriate dosage adjustments need to be made. The monitoring interval varies depending on the stability of the INR, but is usually a few weeks. The standard approach is for the INR to be measured on a blood sample in a hospital laboratory, after which a doctor recommends the dose to take and when the test should be repeated. However, with a home-monitoring device and suitable training, people can manage their own anticoagulation treatment. This is more convenient and empowering for them and potentially reduces costs for healthcare systems. However, it may be unsafe if their INR is further from target than in those people being managed traditionally. This review investigates differences between self-managed anticoagulation and anticoagulation managed by doctors. Self-managed anticoagulation involves adjustment of anticoagulation dose based on self-monitoring results after structured training.1
Review of the evidence Background
Search strategy
People at increased risk of thromboembolism usually take warfarin or other oral anticoagulant
We identified one high quality review by Siebenhofer and colleagues (search date 2002).1 We updated
1744-2249/$ - see front matter & 2005 Elsevier Ltd. All rights reserved. doi:10.1016/j.ehbc.2005.07.004
ARTICLE IN PRESS Self-management of oral anticoagulation this search in May 2005 by searching Medline (2002 to date), EMBASE (2002 to date), and the Cochrane Library (Issue 2 2005).
335
Review findings
Inclusion/exclusion criteria We included English language randomised controlled trials (RCTs) and systematic reviews of RCTs investigating self-management of anticoagulation therapy compared with management by doctors. We excluded studies where INR was tested by patients, but dosing was still decided by a doctor.
Data extraction We extracted data relating to accuracy of anticoagulation, complications such as bleeding or thromboembolism, quality of life, and costs. The review is narrative.
Summary of studies We found one systematic review of four RCTs,1 and four other RCTs.2–6 The studies are described in Table 1. The self-management model used was similar in all of the studies. People initially attended two or three training sessions, and follow-up was started when they were judged to be capable of self-management. The frequency of INR measurements varied, some studies specified every 1 or 2 weeks, and others allowed people to vary the testing frequency based on stability of INR measurements or dose changes. Five studies used management by a primary care doctor as the routine care comparator, and three studies used management in a specialised clinic. The frequency of INR measurement was generally left to the discretion of the doctor. Most studies had a followup of between 3 and 12 months. One study had a longer follow-up of 24–36 months, but the results are not reliable because of poor reporting.7–9 Only one study stipulated indications for anticoagulation (mechanical heart valve implantation7–9). Most studies excluded people with mental illness or physical disability that would have made selfmanagement difficult, although only one study formally assessed people to determine if they would be capable of self-management.6 Most of the studies were good quality, but there were problems in a few studies that reduce the reliability of results: two studies did not have adequate randomisation;10,11 three studies reported only per protocol results;6,10,11 and in two studies, the reporting of results and statistical analysis was poor.7–9,11
The accuracy of anticoagulation control was better with self-management than with routine care in seven of the eight studies. Thromboembolic and bleeding complications were rare in both groups, so the studies were too small to detect a difference between selfmanagement and routine care. One study reported that self-management significantly increased quality of life compared with routine care,12 while another study found no significant difference.6 Two studies reported that quality of life was better compared with baseline in the self-management group, but they did not assess quality of life in the routine care group.3,4,10 There was limited evidence about costs: only one UK study6 and one German study12 estimated the relative costs of self-management and routine care. The German study’s methodology was crude but suggested cost-savings, while the more reliable UK study showed much higher costs with self-management. These arose from the costs of training and the monitoring device. These are one-off costs, so the longer selfmanagement continues, the less important they become.
Self-management can be more accurate than management by doctors in primary care or a specialised clinic, although the differences are not large. Most studies reported a non-significant improvement with self-management, but they were generally powered only to show a difference of 10–20% and so could not detect a smaller difference. A study currently in progress is designed to show whether the two interventions are equivalent, in which the study investigators have specified that a difference below 10% is not clinically important.13 Although accuracy of anticoagulation control is a good proxy outcome, information on clinical outcomes such as thromboembolism or bleeding is lacking. However, it seems implausible that complications could be more common if INRs are better controlled. Thromboembolism and bleeding complications are rare, so much larger studies would be needed to determine the effect of self-management on these events. The evidence on quality of life and cost is limited. However, among those who completed the trials, self-management was reported to improve quality of life, reducing the inconvenience of treatment and increasing treatment satisfaction
ARTICLE IN PRESS 336 Table 1
Bazian Ltd Results of studies.
Key features of study
Main outcomes
Key quality issues
Mene´ndez-Ja ´ndula 2005 Study design: Randomised controlled trial comparing selfmanagement versus specialised clinic routine care Self-management: 368 people; a structured educational programme of two teaching sessions on consecutive days (2 hours), INR measured once a week Routine care: 369 people; monthly appointments at a specialised clinic Follow-up: Median 11.8 months Inclusion criteria: Long-term anticoagulation therapy initiated at least 3 months before study entry, aged 18 years and over
INR within therapeutic range: 58.6% self-management v 55.6% routine care; p ¼ 0.02 Severe haemorrhagic complication: 1.1% self-management v 1.9% routine care Thromboembolic complications: 1.1% self-management v 5.4% routine care Minor haemorrhagic complication: 14.9% self-management v 36.3% routine care Death: 1.6% self-management v 4.1% routine care
21% withdrawal self-management v 2.4% routine care. In the selfmanagement group, the majority of people withdrew before the training because of lack of confidence in their ability to follow the self-management programme.
Gadisseur 2003 and Gadisseur 20043,4 Study design: Randomised controlled trial comparing: selfmanagement; specialised clinic routine care; self-measurement without self-dosing; training followed by routine care Self-management: 47 people; a structured educational programme (4–5 people) of three consecutive weekly teaching sessions (90–120 minutes), INR measured once a week, participant decides on a potential dose change, which is checked by a physician before actually changing the dose Routine care: 161 people; INR measured in a specialised clinic, frequency of measurement dependent on stability of INR values Follow-up: Mean 24.4 weeks Inclusion criteria: Long-term anticoagulation therapy initiated at least 3 months before study entry, aged between 18 and 75 years
INR within therapeutic range: 66.3% self-management v 58.7% routine care; po0.05 Time in target range: 68.6% selfmanagement v 63.5% routine care, not significant Haemorrhagic complications: 2 self-management (1 spontaneous subdural haematoma and 1 traumatic subdural haematoma) v 1 routine care (1 gastrointestinal bleeding) Thromboembolic complications: 0 in both groups Dosing corrections: 5.2% selfmanagement (not applicable to routine care) Change from baseline in quality of life (score 1 ¼ total disagreement to 6 ¼ total agreement, a negative score indicates the item is less often reported): self-management (not reported for routine care) daily hassles –0.31; self-efficacy +0.32; general treatment satisfaction +0.49; distress –0.44; strained social network –0.21
People were selected for the study and randomised before being asked about willingness to participate. The routine care group was not informed about the study at any time. After randomisation, the selfmeasurement, self-management, and trained group were asked to participate in the study. 74.4% of people refused to participate, the main reasons cited were: prefers existing system (33.2%); too old, nervous, or uncertain (24.6%); no time or not interested (29.7%). 21 people also withdrew after the training, but before being randomised to self-management, self-measurement, or training and routine care, generally because of difficulty using the testing devices or working out dosage adjustments. The safety measure of a physician checking dose changes made in the self-management group may have biased the results, as the decision is not managed by the participant alone. However, the number of dosing corrections was low and concerned minor changes, so it is unlikely that this had a major effect on results.
Sunderji 20045 Study design: Randomised controlled trial comparing selfmanagement versus primary care doctor routine care
INR within therapeutic range: 64.8% self-management v 58.7% routine care; p ¼ 0:23 Time in target range: 71.8% selfmanagement v 63.2% routine care;
19% withdrawal self-management v 0% routine care. The main reasons for withdrawal were difficulty operating INR monitor and preference for physician
2
ARTICLE IN PRESS Self-management of oral anticoagulation
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Table 1 (continued) Key features of study
Main outcomes
Key quality issues
Self-management: 69 people; a structured educational programme of two teaching sessions (1–3 hours), and 1–2 weeks between sessions to practice selfmonitoring, weekly testing initially but frequency of testing reduced if INR within the target range for two consecutive measurements, weekly testing resumed if change in dose Routine care: 70 people; frequency of testing and dosing left to the discretion of a primary care doctor Follow-up: 8 months Inclusion criteria: Long-term anticoagulation therapy initiated at least 1 month before study entry, aged 18 years and over, target INR range of 2.0–3.0 or 2.5–3.5
p ¼ 0:14 Major bleeding: 0 self-management v 1 routine care Thromboembolism: 0 selfmanagement v 2 routine care
management. The number of withdrawals reduced the power of the study to detect a significant difference in INR values. The study was also not powered to detect a significant difference in complication rates.
Fitzmaurice 20026 Study design: Randomised controlled trial comparing selfmanagement versus primary care doctor routine care Self-management: 23 people; a structured educational programme of two consecutive weekly teaching sessions (1–2 hours), INR measured every 2 weeks, or after 1 week if dose adjusted Routine care: 26 people; frequency of testing and dosing left to the discretion of a primary care doctor Follow-up: 6 months Inclusion criteria: Long-term anticoagulation therapy initiated at least 6 months before study entry, aged 18 years and over, ability to perform self-management as assessed by a practice nurse
INR within therapeutic range: 66% self-management v 72% routine care; not significant Time in target range: 74% selfmanagement v 77% routine care Minor adverse events: 6 selfmanagement (2 breathlessness, 2 unexplained bruising, 1 haematuria, 1 menorrhagia) v 0 routine care Major adverse events: 0 selfmanagement v 1 routine care (1 fatal retroperitoneal haemorrhage) Mean cost per year: £425 selfmanagement v £90 routine care; po0:001 Quality of life (8 people questioned in each group): No significant difference
Per-protocol analysis, 23% withdrawal self-management v 0% routine care. People were only asked to participate in the study if a practice nurse believed they were capable of performing selfmanagement, based on: previous treatment adherence; physical wellbeing; anxiety; cognitive ability; visual acuity; and ability to follow simple instructions. Only 38% of people receiving warfarin met these criteria and 28% refused to participate. Therefore, the population of this study is not generalisable to the majority of people receiving long-term anticoagulation treatment.
Koertke 2000, Koertke 2001 and Koertke 20017–9 – the first two papers reported the first 600 people to complete 2 year followup after surgery, and the third paper reported 1154 people (including the 600 people from the other papers) Study design: Randomised controlled trial comparing selfmanagement versus primary care doctor usual care
First two papers:7,8 INR within therapeutic range: 78.3% self-management v 60.5% routine care; po0:001 Anticoagulation-induced complications leading to hospital admission: Thromboembolism: 12 selfmanagement v 20 routine care; not significant Bleeding: 17 self-management v 25 routine care; not significant
Discrepancies in reporting of data between papers and high withdrawal rate reduce the reliability of these results. The first paper of 600 people reported more deaths in the first 30 days than the third paper of 1154 people. Withdrawal: 16% in first paper; 15% in second paper; 10% in third paper
ARTICLE IN PRESS 338
Bazian Ltd
Table 1 (continued) Key features of study
Main outcomes
Key quality issues
Self-management: 305 people reported in first two papers, and 579 people reported in third paper; people were trained in selfmanagement from day 6–11 after surgery Routine care: 295 people reported in first two papers, and 575 people reported in third paper; primary care doctor Follow-up: 36 months in first two papers, 24 months in third paper Inclusion criteria: Mechanical heart valve implantation
Third paper:9 INR within therapeutic range: 79.2% self-management v 64.9% routine care; po0:001 Anticoagulation-induced complications leading to hospital admission: Thromboembolism: 16 selfmanagement v 32 routine care; p ¼ 0:026 Bleeding: 42 self-management v 34 routine care; not significant
Cromhoecke 200010 Study design: Randomised controlled crossover trial comparing self-management versus specialised clinic routine care 50 people randomised to selfmanagement followed by routine care, or vice versa Self-management: Structured educational programme (4 to 10 people) of two sessions (2 hours) Routine care: Specialised clinic Follow-up: 3 months Inclusion criteria: Long-term anticoagulation
INR within therapeutic range: 55% self-management v 49% routine care; p ¼ 0:06 Number of people achieving better control in one of the two management strategies: 10 selfmanagement v 5 routine care Major bleeding: 0 in both groups Minor bleeding: 1 self-management v 3 routine care Thromboembolism: 0 selfmanagement v 2 routine care (1 venous, 1 transient ischaemic attack) Change from baseline in quality of life (score 1 ¼ total disagreement to 6 ¼ total agreement): daily worries: 1.8; self-efficacy: +5.4; general treatment satisfaction: +4.8; distress: 2.5; social issues: 1.7 Quality of life also presented for ‘conventional care group’ but this was a matched control group, not randomised, so comparison not reliable
Inadequate allocation concealment (sealed envelopes), per protocol analysis, 1 person withdrew whilst in the self-management stage
Watzke 200011 Study design: Randomised controlled trial comparing selfmanagement versus primary care doctor routine care Self-management: 59 people; structured educational programme (5–10 people) of training in selftesting (2 hours) and training in self-dosing (1 hour), INR measured once a week Routine care: 54 people; people were seen every 4–8 weeks, precise frequency of testing and dosing left to the discretion of a primary care doctor
Squared INR deviation: 0.32 selfmanagement v 0.57 routine care INR within therapeutic range: 84.5% self-management v 73.8% routine care Achieved mean INR in high target group: 3.15 (target INR 3.2) selfmanagement v 3.19 (target INR 3.5) routine care Achieved mean INR in low target group: 2.42 (target INR 2.40) selfmanagement v 2.52 (target INR 2.5) routine care Major bleeding: 1 self-management v 0 routine care Transient ischaemic attack: 1 self-
Statistical analysis poorly reported making results hard to interpret Allocation concealment not reported, per protocol analysis, 17% withdrawal self-management v 2% routine care Only people with stable anticoagulation in the previous 6 months were included, so these results are not generalisable to all people receiving long-term anticoagulation
ARTICLE IN PRESS Self-management of oral anticoagulation
339
Table 1. (continued) Key features of study
Main outcomes
Follow-up: 6 months Inclusion criteria: More than 50% of INR values from the last 6 months had to be in therapeutic range. Within each group, people were given high (INR 2.5 to 4.5) or low (INR 2–3) anticoagulation targets
management v 0 routine care
Sawicki 199812 Study design: Single-blind, multicentre, randomized controlled trial comparing selfmanagement versus primary care doctor routine care Self-management: 90 people; a structured educational programme (3–6 people) of three consecutive weekly teaching sessions (60–90 minutes), INR measured 1–2 times a week Routine care: 89 people; twice monthly appointments with a primary care doctor Follow-up: 6 months Inclusion criteria: Long-term anticoagulation
INR within therapeutic range: 53% self-management v 43.2% routine care; p ¼ 0:22 Squared INR deviation: 0.65 selfmanagement v 0.83 routine care; p ¼ 0:03 Major bleeding: 1 self-management v 1 routine care Minor bleeding: 12 selfmanagement v 10 routine care Major thromboembolism complication: 0 self-management v 2 routine care Minor thromboembolism complication: 1 self-management v 0 routine care Death: 1 self-management v 1 routine care Change from baseline in quality of life (score 1 ¼ total disagreement to 6 ¼ total agreement, a negative score indicates the item is less often reported) Daily hassles: –0.49 selfmanagement v –0.03 routine care (p ¼ 0:01); self-efficacy: +0.83 selfmanagement v +0.35 routine care (p ¼ 0:003); general treatment satisfaction: +1.54 self-management v +0.24 routine care (po0:001); distress: –0.61 self-management v –0.21 routine care (p ¼ 0:008); strained social network: –0.40 selfmanagement v –0.23 routine care (p ¼ 0:19)Cost: 9 European Currency Units (ECUs) for 1 INR measurement (468–936 ECUs per year) v 16 ECUs for 1 visit to doctor (384 ECUs per year)
and self-efficacy. The cost of measuring INR was reported to be greater with self-management than management by doctors. Further cost evaluations are needed, including modeling the
Key quality issues
8% withdrawal self-management v 8% routine care Cost analysis crude
cost of treating thromboembolism and bleeding complications, as any difference in these events between interventions would affect the overall cost.
ARTICLE IN PRESS 340 As anticoagulation treatment is often life-long, the sustainability of self-management is important. Withdrawal in the first 3–12 months tended to be higher with self-management compared with routine care (about 20% v about 2%). The most common reasons given for withdrawal were difficulties mastering self-management techniques, lack of confidence in performing self-management, or preference for management by a doctor. Selfmanagement is not suitable for everyone who requires long-term anticoagulation, although a more extensive training programme may help people overcome difficulties or reservations about self-management. Further investigation is needed to determine to whom self-management should be offered. Longer term sustainability may be better than that seen in the short term according to one of the studies, which provided 5-year uncontrolled followup data.12,14 People initially randomised to routine care were subsequently offered self-management after 6 months, and both groups continued with self-management for 5 years. Of 178 people offered self-management, 19 people died and 4 ceased anticoagulation treatment before the end of the 5year follow-up, and 5 refused to participate in the final evaluation. Among the remaining participants, 89% were happy to continue with self-management and only 11% chose to return to management by a doctor. During the fifth year of follow-up, 62% of INRs were in therapeutic range, and over the 5 years, the risk of complications were 0.62/100 person-years for severe bleeding and 1.1/100 person-years for thromboembolism. The 5-year follow-up data show that self-management is sustainable in the long term, with similar accuracy of anticoagulation control to that reported in the comparative studies. Taken together, these studies show that selfmanagement of anti-coagulation is feasible and acceptable to patients and can be more accurate than management by doctors. There remain uncertainties about patient selection and cost-effectiveness.
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References 1. Siebenhofer A, Berghold A, Sawicki PT. Systematic review of studies of self-management of oral anticoagulation. Thromb Haemost 2004;91:225–32. 2. Menendez-Jandula B, Souto JC, Oliver A, et al. Comparing selfmanagement of oral anticoagulant therapy with clinic management: a randomized trial. Ann Intern Med 2005;142:1–10. 3. Gadisseur AP, Breukink-Engbers WG, van der Meer FJ, et al. Comparison of the quality of oral anticoagulant therapy through patient self-management and management by specialized anticoagulation clinics in the Netherlands: a randomized clinical trial. Arch Intern Med 2003;163:2639–46. 4. Gadisseur AP, Kaptein AA, Breukink-Engbers WG, et al. Patient self-management of oral anticoagulant care vs. management by specialized anticoagulation clinics: positive effects on quality of life. J Thromb Haemost 2004;2:584–91. 5. Sunderji R, Gin K, Shalansky K, et al. A randomized trial of patient self-managed versus physician-managed oral anticoagulation. Can J Cardiol 2004;20:1117–23. 6. Fitzmaurice DA, Murray ET, Gee KM, et al. A randomised controlled trial of patient self-management of oral anticoagulation treatment compared with primary care management. J Clin Pathol 2002;55:845. 7. Koertke H, Minami K, Bairaktaris A, et al. INR self-management following mechanical heart valve replacement. J Thromb Thrombolysis 2000;9(Suppl 1):S41–5. 8. Kortke H, Korfer R. International normalized ratio selfmanagement after mechanical heart valve replacement: is an early start advantageous? Ann Thorac Surg 2001;72:44–8. 9. Ko ¨rtke H, Minami K, Breymann T, et al. INR-Selbstmanagement nach mechanischem Herzklappenersatz: ESCAT (Early Self Controlled Anticoagulation Trial). Z Kardiol 2001; 90(Suppl 6):118–24. 10. Cromhoecke ME, Levi M, Colly LP, et al. Oral anticoagulation self-management and management by a specialist anticoagulation clinic: a randomised cross-over comparison. Lancet 2000;356:97–102. 11. Watzke HH, Forburg E, Svolba G, et al. A prospective controlled trial comparing weekly self-testing and selfdosing with the standard management of patients on stable oral anticoagulation. Thromb Haemost 2000;83:661–5. 12. Sawicki PT. for the working group for the study of patient self-management of oral anticoagulation. A structured teaching and self-management program for patients receiving oral anticoagulation. JAMA 1999;281:145–50. 13. McCahon D, Fitzmaurice DA, Murray ET, et al. Study protocol: SMART: Self-management of anticoagulation, a randomised trial. BMC Family Practice 2003;4:11. 14. Sawicki PT, Gla ¨ser B, Kleespies C, et al. Long-term results of patients’ self-management of oral anticoagulation. J Clin Bas Cardiol 2003;6:59–62.
www.elsevier.com/locate/ebhph
SYSTEMATIC REVIEW
Self-management of oral anticoagulation Bazian Ltd London, UK
Key points
Many people need long-term anticoagulation treatment to reduce their risk of thromboembolism. The dose of anticoagulant drug required varies unpredictably between individuals and over time. Poor anticoagulation control leads to either inadequate protection against thromboembolism or increased risk of life-threatening bleeding. The degree of anticoagulation needs to be regularly monitored, and the dosage of anticoagulant changed if necessary. Individuals managing their own anticoagulation is feasible, can be more accurate than management by doctors and is acceptable to patients. There remain uncertainties about patient selection and cost-effectiveness. The evidence on quality of life and cost is limited. However, the available evidence suggests self-management is likely to improve quality of life, but may cost more than management by doctors. Difficulties with self-management techniques, lack of confidence in ability to perform self-management, and preference for management by doctors were reported by people withdrawing from the studies, so self-management is not suitable for all people needing long-term anticoagulation.
drugs to reduce their risk, but the dose required varies unpredictably between individuals and over time. Too high a dose leads to a risk of lifethreatening bleeding, while too low a dose will not adequately treat the underlying condition. Therefore, the degree of anticoagulation (expressed as the international normalised ratio; INR), needs monitoring, and appropriate dosage adjustments need to be made. The monitoring interval varies depending on the stability of the INR, but is usually a few weeks. The standard approach is for the INR to be measured on a blood sample in a hospital laboratory, after which a doctor recommends the dose to take and when the test should be repeated. However, with a home-monitoring device and suitable training, people can manage their own anticoagulation treatment. This is more convenient and empowering for them and potentially reduces costs for healthcare systems. However, it may be unsafe if their INR is further from target than in those people being managed traditionally. This review investigates differences between self-managed anticoagulation and anticoagulation managed by doctors. Self-managed anticoagulation involves adjustment of anticoagulation dose based on self-monitoring results after structured training.1
Review of the evidence Background
Search strategy
People at increased risk of thromboembolism usually take warfarin or other oral anticoagulant
We identified one high quality review by Siebenhofer and colleagues (search date 2002).1 We updated
1744-2249/$ - see front matter & 2005 Elsevier Ltd. All rights reserved. doi:10.1016/j.ehbc.2005.07.004
ARTICLE IN PRESS Self-management of oral anticoagulation this search in May 2005 by searching Medline (2002 to date), EMBASE (2002 to date), and the Cochrane Library (Issue 2 2005).
335
Review findings
Inclusion/exclusion criteria We included English language randomised controlled trials (RCTs) and systematic reviews of RCTs investigating self-management of anticoagulation therapy compared with management by doctors. We excluded studies where INR was tested by patients, but dosing was still decided by a doctor.
Data extraction We extracted data relating to accuracy of anticoagulation, complications such as bleeding or thromboembolism, quality of life, and costs. The review is narrative.
Summary of studies We found one systematic review of four RCTs,1 and four other RCTs.2–6 The studies are described in Table 1. The self-management model used was similar in all of the studies. People initially attended two or three training sessions, and follow-up was started when they were judged to be capable of self-management. The frequency of INR measurements varied, some studies specified every 1 or 2 weeks, and others allowed people to vary the testing frequency based on stability of INR measurements or dose changes. Five studies used management by a primary care doctor as the routine care comparator, and three studies used management in a specialised clinic. The frequency of INR measurement was generally left to the discretion of the doctor. Most studies had a followup of between 3 and 12 months. One study had a longer follow-up of 24–36 months, but the results are not reliable because of poor reporting.7–9 Only one study stipulated indications for anticoagulation (mechanical heart valve implantation7–9). Most studies excluded people with mental illness or physical disability that would have made selfmanagement difficult, although only one study formally assessed people to determine if they would be capable of self-management.6 Most of the studies were good quality, but there were problems in a few studies that reduce the reliability of results: two studies did not have adequate randomisation;10,11 three studies reported only per protocol results;6,10,11 and in two studies, the reporting of results and statistical analysis was poor.7–9,11
The accuracy of anticoagulation control was better with self-management than with routine care in seven of the eight studies. Thromboembolic and bleeding complications were rare in both groups, so the studies were too small to detect a difference between selfmanagement and routine care. One study reported that self-management significantly increased quality of life compared with routine care,12 while another study found no significant difference.6 Two studies reported that quality of life was better compared with baseline in the self-management group, but they did not assess quality of life in the routine care group.3,4,10 There was limited evidence about costs: only one UK study6 and one German study12 estimated the relative costs of self-management and routine care. The German study’s methodology was crude but suggested cost-savings, while the more reliable UK study showed much higher costs with self-management. These arose from the costs of training and the monitoring device. These are one-off costs, so the longer selfmanagement continues, the less important they become.
Self-management can be more accurate than management by doctors in primary care or a specialised clinic, although the differences are not large. Most studies reported a non-significant improvement with self-management, but they were generally powered only to show a difference of 10–20% and so could not detect a smaller difference. A study currently in progress is designed to show whether the two interventions are equivalent, in which the study investigators have specified that a difference below 10% is not clinically important.13 Although accuracy of anticoagulation control is a good proxy outcome, information on clinical outcomes such as thromboembolism or bleeding is lacking. However, it seems implausible that complications could be more common if INRs are better controlled. Thromboembolism and bleeding complications are rare, so much larger studies would be needed to determine the effect of self-management on these events. The evidence on quality of life and cost is limited. However, among those who completed the trials, self-management was reported to improve quality of life, reducing the inconvenience of treatment and increasing treatment satisfaction
ARTICLE IN PRESS 336 Table 1
Bazian Ltd Results of studies.
Key features of study
Main outcomes
Key quality issues
Mene´ndez-Ja ´ndula 2005 Study design: Randomised controlled trial comparing selfmanagement versus specialised clinic routine care Self-management: 368 people; a structured educational programme of two teaching sessions on consecutive days (2 hours), INR measured once a week Routine care: 369 people; monthly appointments at a specialised clinic Follow-up: Median 11.8 months Inclusion criteria: Long-term anticoagulation therapy initiated at least 3 months before study entry, aged 18 years and over
INR within therapeutic range: 58.6% self-management v 55.6% routine care; p ¼ 0.02 Severe haemorrhagic complication: 1.1% self-management v 1.9% routine care Thromboembolic complications: 1.1% self-management v 5.4% routine care Minor haemorrhagic complication: 14.9% self-management v 36.3% routine care Death: 1.6% self-management v 4.1% routine care
21% withdrawal self-management v 2.4% routine care. In the selfmanagement group, the majority of people withdrew before the training because of lack of confidence in their ability to follow the self-management programme.
Gadisseur 2003 and Gadisseur 20043,4 Study design: Randomised controlled trial comparing: selfmanagement; specialised clinic routine care; self-measurement without self-dosing; training followed by routine care Self-management: 47 people; a structured educational programme (4–5 people) of three consecutive weekly teaching sessions (90–120 minutes), INR measured once a week, participant decides on a potential dose change, which is checked by a physician before actually changing the dose Routine care: 161 people; INR measured in a specialised clinic, frequency of measurement dependent on stability of INR values Follow-up: Mean 24.4 weeks Inclusion criteria: Long-term anticoagulation therapy initiated at least 3 months before study entry, aged between 18 and 75 years
INR within therapeutic range: 66.3% self-management v 58.7% routine care; po0.05 Time in target range: 68.6% selfmanagement v 63.5% routine care, not significant Haemorrhagic complications: 2 self-management (1 spontaneous subdural haematoma and 1 traumatic subdural haematoma) v 1 routine care (1 gastrointestinal bleeding) Thromboembolic complications: 0 in both groups Dosing corrections: 5.2% selfmanagement (not applicable to routine care) Change from baseline in quality of life (score 1 ¼ total disagreement to 6 ¼ total agreement, a negative score indicates the item is less often reported): self-management (not reported for routine care) daily hassles –0.31; self-efficacy +0.32; general treatment satisfaction +0.49; distress –0.44; strained social network –0.21
People were selected for the study and randomised before being asked about willingness to participate. The routine care group was not informed about the study at any time. After randomisation, the selfmeasurement, self-management, and trained group were asked to participate in the study. 74.4% of people refused to participate, the main reasons cited were: prefers existing system (33.2%); too old, nervous, or uncertain (24.6%); no time or not interested (29.7%). 21 people also withdrew after the training, but before being randomised to self-management, self-measurement, or training and routine care, generally because of difficulty using the testing devices or working out dosage adjustments. The safety measure of a physician checking dose changes made in the self-management group may have biased the results, as the decision is not managed by the participant alone. However, the number of dosing corrections was low and concerned minor changes, so it is unlikely that this had a major effect on results.
Sunderji 20045 Study design: Randomised controlled trial comparing selfmanagement versus primary care doctor routine care
INR within therapeutic range: 64.8% self-management v 58.7% routine care; p ¼ 0:23 Time in target range: 71.8% selfmanagement v 63.2% routine care;
19% withdrawal self-management v 0% routine care. The main reasons for withdrawal were difficulty operating INR monitor and preference for physician
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Table 1 (continued) Key features of study
Main outcomes
Key quality issues
Self-management: 69 people; a structured educational programme of two teaching sessions (1–3 hours), and 1–2 weeks between sessions to practice selfmonitoring, weekly testing initially but frequency of testing reduced if INR within the target range for two consecutive measurements, weekly testing resumed if change in dose Routine care: 70 people; frequency of testing and dosing left to the discretion of a primary care doctor Follow-up: 8 months Inclusion criteria: Long-term anticoagulation therapy initiated at least 1 month before study entry, aged 18 years and over, target INR range of 2.0–3.0 or 2.5–3.5
p ¼ 0:14 Major bleeding: 0 self-management v 1 routine care Thromboembolism: 0 selfmanagement v 2 routine care
management. The number of withdrawals reduced the power of the study to detect a significant difference in INR values. The study was also not powered to detect a significant difference in complication rates.
Fitzmaurice 20026 Study design: Randomised controlled trial comparing selfmanagement versus primary care doctor routine care Self-management: 23 people; a structured educational programme of two consecutive weekly teaching sessions (1–2 hours), INR measured every 2 weeks, or after 1 week if dose adjusted Routine care: 26 people; frequency of testing and dosing left to the discretion of a primary care doctor Follow-up: 6 months Inclusion criteria: Long-term anticoagulation therapy initiated at least 6 months before study entry, aged 18 years and over, ability to perform self-management as assessed by a practice nurse
INR within therapeutic range: 66% self-management v 72% routine care; not significant Time in target range: 74% selfmanagement v 77% routine care Minor adverse events: 6 selfmanagement (2 breathlessness, 2 unexplained bruising, 1 haematuria, 1 menorrhagia) v 0 routine care Major adverse events: 0 selfmanagement v 1 routine care (1 fatal retroperitoneal haemorrhage) Mean cost per year: £425 selfmanagement v £90 routine care; po0:001 Quality of life (8 people questioned in each group): No significant difference
Per-protocol analysis, 23% withdrawal self-management v 0% routine care. People were only asked to participate in the study if a practice nurse believed they were capable of performing selfmanagement, based on: previous treatment adherence; physical wellbeing; anxiety; cognitive ability; visual acuity; and ability to follow simple instructions. Only 38% of people receiving warfarin met these criteria and 28% refused to participate. Therefore, the population of this study is not generalisable to the majority of people receiving long-term anticoagulation treatment.
Koertke 2000, Koertke 2001 and Koertke 20017–9 – the first two papers reported the first 600 people to complete 2 year followup after surgery, and the third paper reported 1154 people (including the 600 people from the other papers) Study design: Randomised controlled trial comparing selfmanagement versus primary care doctor usual care
First two papers:7,8 INR within therapeutic range: 78.3% self-management v 60.5% routine care; po0:001 Anticoagulation-induced complications leading to hospital admission: Thromboembolism: 12 selfmanagement v 20 routine care; not significant Bleeding: 17 self-management v 25 routine care; not significant
Discrepancies in reporting of data between papers and high withdrawal rate reduce the reliability of these results. The first paper of 600 people reported more deaths in the first 30 days than the third paper of 1154 people. Withdrawal: 16% in first paper; 15% in second paper; 10% in third paper
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Table 1 (continued) Key features of study
Main outcomes
Key quality issues
Self-management: 305 people reported in first two papers, and 579 people reported in third paper; people were trained in selfmanagement from day 6–11 after surgery Routine care: 295 people reported in first two papers, and 575 people reported in third paper; primary care doctor Follow-up: 36 months in first two papers, 24 months in third paper Inclusion criteria: Mechanical heart valve implantation
Third paper:9 INR within therapeutic range: 79.2% self-management v 64.9% routine care; po0:001 Anticoagulation-induced complications leading to hospital admission: Thromboembolism: 16 selfmanagement v 32 routine care; p ¼ 0:026 Bleeding: 42 self-management v 34 routine care; not significant
Cromhoecke 200010 Study design: Randomised controlled crossover trial comparing self-management versus specialised clinic routine care 50 people randomised to selfmanagement followed by routine care, or vice versa Self-management: Structured educational programme (4 to 10 people) of two sessions (2 hours) Routine care: Specialised clinic Follow-up: 3 months Inclusion criteria: Long-term anticoagulation
INR within therapeutic range: 55% self-management v 49% routine care; p ¼ 0:06 Number of people achieving better control in one of the two management strategies: 10 selfmanagement v 5 routine care Major bleeding: 0 in both groups Minor bleeding: 1 self-management v 3 routine care Thromboembolism: 0 selfmanagement v 2 routine care (1 venous, 1 transient ischaemic attack) Change from baseline in quality of life (score 1 ¼ total disagreement to 6 ¼ total agreement): daily worries: 1.8; self-efficacy: +5.4; general treatment satisfaction: +4.8; distress: 2.5; social issues: 1.7 Quality of life also presented for ‘conventional care group’ but this was a matched control group, not randomised, so comparison not reliable
Inadequate allocation concealment (sealed envelopes), per protocol analysis, 1 person withdrew whilst in the self-management stage
Watzke 200011 Study design: Randomised controlled trial comparing selfmanagement versus primary care doctor routine care Self-management: 59 people; structured educational programme (5–10 people) of training in selftesting (2 hours) and training in self-dosing (1 hour), INR measured once a week Routine care: 54 people; people were seen every 4–8 weeks, precise frequency of testing and dosing left to the discretion of a primary care doctor
Squared INR deviation: 0.32 selfmanagement v 0.57 routine care INR within therapeutic range: 84.5% self-management v 73.8% routine care Achieved mean INR in high target group: 3.15 (target INR 3.2) selfmanagement v 3.19 (target INR 3.5) routine care Achieved mean INR in low target group: 2.42 (target INR 2.40) selfmanagement v 2.52 (target INR 2.5) routine care Major bleeding: 1 self-management v 0 routine care Transient ischaemic attack: 1 self-
Statistical analysis poorly reported making results hard to interpret Allocation concealment not reported, per protocol analysis, 17% withdrawal self-management v 2% routine care Only people with stable anticoagulation in the previous 6 months were included, so these results are not generalisable to all people receiving long-term anticoagulation
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Table 1. (continued) Key features of study
Main outcomes
Follow-up: 6 months Inclusion criteria: More than 50% of INR values from the last 6 months had to be in therapeutic range. Within each group, people were given high (INR 2.5 to 4.5) or low (INR 2–3) anticoagulation targets
management v 0 routine care
Sawicki 199812 Study design: Single-blind, multicentre, randomized controlled trial comparing selfmanagement versus primary care doctor routine care Self-management: 90 people; a structured educational programme (3–6 people) of three consecutive weekly teaching sessions (60–90 minutes), INR measured 1–2 times a week Routine care: 89 people; twice monthly appointments with a primary care doctor Follow-up: 6 months Inclusion criteria: Long-term anticoagulation
INR within therapeutic range: 53% self-management v 43.2% routine care; p ¼ 0:22 Squared INR deviation: 0.65 selfmanagement v 0.83 routine care; p ¼ 0:03 Major bleeding: 1 self-management v 1 routine care Minor bleeding: 12 selfmanagement v 10 routine care Major thromboembolism complication: 0 self-management v 2 routine care Minor thromboembolism complication: 1 self-management v 0 routine care Death: 1 self-management v 1 routine care Change from baseline in quality of life (score 1 ¼ total disagreement to 6 ¼ total agreement, a negative score indicates the item is less often reported) Daily hassles: –0.49 selfmanagement v –0.03 routine care (p ¼ 0:01); self-efficacy: +0.83 selfmanagement v +0.35 routine care (p ¼ 0:003); general treatment satisfaction: +1.54 self-management v +0.24 routine care (po0:001); distress: –0.61 self-management v –0.21 routine care (p ¼ 0:008); strained social network: –0.40 selfmanagement v –0.23 routine care (p ¼ 0:19)Cost: 9 European Currency Units (ECUs) for 1 INR measurement (468–936 ECUs per year) v 16 ECUs for 1 visit to doctor (384 ECUs per year)
and self-efficacy. The cost of measuring INR was reported to be greater with self-management than management by doctors. Further cost evaluations are needed, including modeling the
Key quality issues
8% withdrawal self-management v 8% routine care Cost analysis crude
cost of treating thromboembolism and bleeding complications, as any difference in these events between interventions would affect the overall cost.
ARTICLE IN PRESS 340 As anticoagulation treatment is often life-long, the sustainability of self-management is important. Withdrawal in the first 3–12 months tended to be higher with self-management compared with routine care (about 20% v about 2%). The most common reasons given for withdrawal were difficulties mastering self-management techniques, lack of confidence in performing self-management, or preference for management by a doctor. Selfmanagement is not suitable for everyone who requires long-term anticoagulation, although a more extensive training programme may help people overcome difficulties or reservations about self-management. Further investigation is needed to determine to whom self-management should be offered. Longer term sustainability may be better than that seen in the short term according to one of the studies, which provided 5-year uncontrolled followup data.12,14 People initially randomised to routine care were subsequently offered self-management after 6 months, and both groups continued with self-management for 5 years. Of 178 people offered self-management, 19 people died and 4 ceased anticoagulation treatment before the end of the 5year follow-up, and 5 refused to participate in the final evaluation. Among the remaining participants, 89% were happy to continue with self-management and only 11% chose to return to management by a doctor. During the fifth year of follow-up, 62% of INRs were in therapeutic range, and over the 5 years, the risk of complications were 0.62/100 person-years for severe bleeding and 1.1/100 person-years for thromboembolism. The 5-year follow-up data show that self-management is sustainable in the long term, with similar accuracy of anticoagulation control to that reported in the comparative studies. Taken together, these studies show that selfmanagement of anti-coagulation is feasible and acceptable to patients and can be more accurate than management by doctors. There remain uncertainties about patient selection and cost-effectiveness.
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