NIHR Signal Self-monitoring of warfarin is safe and cost-effective

Published on 21 August 2015

This NIHR-funded systematic review investigated the clinical and cost-effectiveness of self-monitoring by people receiving long-term anticoagulation using vitamin K antagonists, most commonly, warfarin. People receiving warfarin require regular blood tests to see how their blood is clotting and to adjust their dose to avoid bleeding from too high a dose or thrombosis (clots) if the dose drops too low. This is usually done at their GP practice or in hospital clinics. Self-monitoring involves two aspects of care; people self-testing their blood on a machine at home and self-managing, adjusting their warfarin dosage themselves.

This review found self-monitoring halved the number of blood clots compared with standard care. Health and social costs were more equal, but the two devices had an 80% chance of being value for money at the usual threshold for the NHS. Self-monitoring could be offered to people who would like to self-monitor, and where they, or their carer, are able to do so.

Share your views on the research.

Why was this study needed?

Oral anticoagulants are used to treat a variety of heart and blood vessel conditions that raise the risk of blood clots and stroke.  These drugs “thin the blood” helping to lower the risk of blood clots. But they also raise the risk of bleeding.

Around 1.4% of UK adults require long-term oral anticoagulant therapy. Warfarin is the most commonly prescribed.

People taking warfarin require regular blood tests to monitor whether they are striking a safe balance between preventing blood clots and raising the risk of bleeding. These might be needed every week, or up to every eight weeks, and usually involve a trip to the GP practice or hospital clinic.

Self-monitoring allows people to monitor themselves (self-test) and adjust their warfarin dose (self-management) at home. This is potentially more convenient for the person, and benefits the NHS by reducing costs associated with GP or hospital visits.

The NIHR-funded this systematic review for NICE to help with producing guidance on the use of self-monitoring.

What did this study do?

This systematic review of randomised controlled trials that evaluated the clinical and cost effectiveness of self-monitoring using three blood monitoring systems: CoaguChek®, INRatio2® PT/INR monitor and ProTime Microagulation system®. The review included trials comparing these self-monitoring systems with standard care, monitoring by GP or hospital clinics, in people needing long-term anticoagulation because of atrial fibrillation (irregular and often fast heartbeat) or heart valve disease.

The systematic review was well designed. However, the authors note that the definition of standard care varied greatly between studies. This means different studies may not have been comparing like with like. 22 of the 26 trials included were judged to be at medium or high risk of bias, so this bias within the studies may affect the reliability of the results.

What did it find?

  • 26 trials were included in the clinical effectiveness review; the majority (22 trials) evaluated the CoaguChek® system.
  • Self-monitoring led to almost a halving of blood clots compared with standard care (relative risk [RR] 0.58, 95% confidence interval [CI] 0.40 to 0.84). There were 54 thromboses among 2403 people self-monitoring, compared to 106 of 2237 on standard care.  There was no significant difference in the number of bleeds (major and minor) between self-monitoring and standard care.
  • Looking specifically at people with artificial heart valves: testing combined with adjustment of anticoagulant dose halved the risk of blood clots (RR 0.56, 95% CI 0.38 to 0.82) and death from any cause (RR 0.54, 95% CI 0.32 to 0.92) compared with standard care. There was no significant difference for people who were self-testing only, without adjusting the dose.
  • There was little difference in the total health and social care costs at 10 years between self-monitoring (£7,333 CoaguChek®, £7,295 InRatio2®, £8,609 ProTime) and standard care (£7,324). They estimated the number of blood clots would be 2.4% lower at 10 years using self-monitoring compared with standard care. Improved clinical outcomes would off-set initial and on-going costs of self-monitoring, such as training costs and annual device cost. Driven by the reduced number of clots, self-monitoring with CoaguChek XS® or INRatio2® had about an 80% chance of being cost-effective at the usual threshold ratio of £20,000 per QALY gained.
  • The proportion of blood test results staying within the recommended range was comparable for self-monitoring (52 to 80%) and standard care (55 to 77%). Adherence was generally high for self-monitoring (around 90% across 13 trials) and preference for self-monitoring was high (77 to 98% in four trials). Few people reported difficulties in using the self-monitoring devices.

What does current guidance say on this issue?

2014 NICE guidance recommends the use of the CoaguChek® or INRatio2® PT/INR by people with atrial fibrillation or heart valve disease, who would prefer to self-monitor, and if they or their carer are physically and cognitively capable of self-monitoring. These recommendations are based on the findings of this systematic review, combined with the expertise of the Diagnostics Advisory Committee.

What are the implications?

The findings of this systematic review informed 2014 NICE guidance, recommending that self-monitoring be offered option to people with atrial fibrillation or heart valve disease who would like to self-monitor and where either they – or their carer – are able to do so.

Non-vitamin K anticoagulants are available. They require less monitoring and dose adjustment but are not suitable for everyone, so vitamin K antagonists are still needed. This systematic review found that self-monitoring was clinically effective at reducing blood clots and was cost-effective compared with standard care, monitoring by either a GP or hospital clinic.

Bibliography

British Heart Foundation. Warfarin. London: British Heart Foundation; no update date given.

Heneghan C, Ward A, Perera R et al. Self-monitoring of oral anticoagulation: systematic review and meta-analysis of individual patient data. Lancet 2012;379(9813):322-34.

Heneghan CJ, Garcia‐Alamino JM, Spencer EA, et al. Self‐monitoring and self‐management of oral anticoagulation. Cochrane Database Syst Rev. 2016;(7):CD003839.

NHS Choices. Anticoagulants, warfarin. London: Department of Health; updated 2013.

NICE. Atrial fibrillation and heart valve disease: self‑monitoring coagulation status using point‑of‑care coagulometers (the CoaguChek XS system and the INRatio2 PT/INR monitor). DG14. London: National Institute for Health and Care Excellence; 2014.

Tompson A, Heneghan C, Fitzmaurice D et al. Supporting patients to self-monitor their oral anticoagulation therapy: recommendations based on a qualitative study of patients' experiences.  Br J Gen Pract 2014;65(636):e438-46.

Ward A, Tompson A, Fitzmaurice D et al. Cohort study of Anticoagulation Self-Monitoring (CASM): a prospective study of its effectiveness in the community. Br J Gen Pract 2015;65(636):e428-37.

Why was this study needed?

Oral anticoagulants are used to treat a variety of heart and blood vessel conditions that raise the risk of blood clots and stroke.  These drugs “thin the blood” helping to lower the risk of blood clots. But they also raise the risk of bleeding.

Around 1.4% of UK adults require long-term oral anticoagulant therapy. Warfarin is the most commonly prescribed.

People taking warfarin require regular blood tests to monitor whether they are striking a safe balance between preventing blood clots and raising the risk of bleeding. These might be needed every week, or up to every eight weeks, and usually involve a trip to the GP practice or hospital clinic.

Self-monitoring allows people to monitor themselves (self-test) and adjust their warfarin dose (self-management) at home. This is potentially more convenient for the person, and benefits the NHS by reducing costs associated with GP or hospital visits.

The NIHR-funded this systematic review for NICE to help with producing guidance on the use of self-monitoring.

What did this study do?

This systematic review of randomised controlled trials that evaluated the clinical and cost effectiveness of self-monitoring using three blood monitoring systems: CoaguChek®, INRatio2® PT/INR monitor and ProTime Microagulation system®. The review included trials comparing these self-monitoring systems with standard care, monitoring by GP or hospital clinics, in people needing long-term anticoagulation because of atrial fibrillation (irregular and often fast heartbeat) or heart valve disease.

The systematic review was well designed. However, the authors note that the definition of standard care varied greatly between studies. This means different studies may not have been comparing like with like. 22 of the 26 trials included were judged to be at medium or high risk of bias, so this bias within the studies may affect the reliability of the results.

What did it find?

  • 26 trials were included in the clinical effectiveness review; the majority (22 trials) evaluated the CoaguChek® system.
  • Self-monitoring led to almost a halving of blood clots compared with standard care (relative risk [RR] 0.58, 95% confidence interval [CI] 0.40 to 0.84). There were 54 thromboses among 2403 people self-monitoring, compared to 106 of 2237 on standard care.  There was no significant difference in the number of bleeds (major and minor) between self-monitoring and standard care.
  • Looking specifically at people with artificial heart valves: testing combined with adjustment of anticoagulant dose halved the risk of blood clots (RR 0.56, 95% CI 0.38 to 0.82) and death from any cause (RR 0.54, 95% CI 0.32 to 0.92) compared with standard care. There was no significant difference for people who were self-testing only, without adjusting the dose.
  • There was little difference in the total health and social care costs at 10 years between self-monitoring (£7,333 CoaguChek®, £7,295 InRatio2®, £8,609 ProTime) and standard care (£7,324). They estimated the number of blood clots would be 2.4% lower at 10 years using self-monitoring compared with standard care. Improved clinical outcomes would off-set initial and on-going costs of self-monitoring, such as training costs and annual device cost. Driven by the reduced number of clots, self-monitoring with CoaguChek XS® or INRatio2® had about an 80% chance of being cost-effective at the usual threshold ratio of £20,000 per QALY gained.
  • The proportion of blood test results staying within the recommended range was comparable for self-monitoring (52 to 80%) and standard care (55 to 77%). Adherence was generally high for self-monitoring (around 90% across 13 trials) and preference for self-monitoring was high (77 to 98% in four trials). Few people reported difficulties in using the self-monitoring devices.

What does current guidance say on this issue?

2014 NICE guidance recommends the use of the CoaguChek® or INRatio2® PT/INR by people with atrial fibrillation or heart valve disease, who would prefer to self-monitor, and if they or their carer are physically and cognitively capable of self-monitoring. These recommendations are based on the findings of this systematic review, combined with the expertise of the Diagnostics Advisory Committee.

What are the implications?

The findings of this systematic review informed 2014 NICE guidance, recommending that self-monitoring be offered option to people with atrial fibrillation or heart valve disease who would like to self-monitor and where either they – or their carer – are able to do so.

Non-vitamin K anticoagulants are available. They require less monitoring and dose adjustment but are not suitable for everyone, so vitamin K antagonists are still needed. This systematic review found that self-monitoring was clinically effective at reducing blood clots and was cost-effective compared with standard care, monitoring by either a GP or hospital clinic.

Bibliography

British Heart Foundation. Warfarin. London: British Heart Foundation; no update date given.

Heneghan C, Ward A, Perera R et al. Self-monitoring of oral anticoagulation: systematic review and meta-analysis of individual patient data. Lancet 2012;379(9813):322-34.

Heneghan CJ, Garcia‐Alamino JM, Spencer EA, et al. Self‐monitoring and self‐management of oral anticoagulation. Cochrane Database Syst Rev. 2016;(7):CD003839.

NHS Choices. Anticoagulants, warfarin. London: Department of Health; updated 2013.

NICE. Atrial fibrillation and heart valve disease: self‑monitoring coagulation status using point‑of‑care coagulometers (the CoaguChek XS system and the INRatio2 PT/INR monitor). DG14. London: National Institute for Health and Care Excellence; 2014.

Tompson A, Heneghan C, Fitzmaurice D et al. Supporting patients to self-monitor their oral anticoagulation therapy: recommendations based on a qualitative study of patients' experiences.  Br J Gen Pract 2014;65(636):e438-46.

Ward A, Tompson A, Fitzmaurice D et al. Cohort study of Anticoagulation Self-Monitoring (CASM): a prospective study of its effectiveness in the community. Br J Gen Pract 2015;65(636):e428-37.

The clinical effectiveness and cost-effectiveness of point-of-care tests (CoaguChek system, INRatio2 PT/INR monitor and ProTime Microcoagulation system) for the self-monitoring of the coagulation status of people receiving long-term vitamin K antagonist therapy, compared with standard UK practice: systematic review and economic evaluation

Published on 4 July 2015

Sharma, P.,Scotland, G.,Cruickshank, M.,Tassie, E.,Fraser, C.,Burton, C.,Croal, B.,Ramsay, C. R.,Brazzelli, M.

Health Technol Assess Volume 19 , 2015

BACKGROUND: Self-monitoring (self-testing and self-management) could be a valid option for oral anticoagulation therapy monitoring in the NHS, but current evidence on its clinical effectiveness or cost-effectiveness is limited. OBJECTIVES: We investigated the clinical effectiveness and cost-effectiveness of point-of-care coagulometers for the self-monitoring of coagulation status in people receiving long-term vitamin K antagonist therapy, compared with standard clinic monitoring. DATA SOURCES: We searched major electronic databases (e.g. MEDLINE, MEDLINE In Process & Other Non-Indexed Citations, EMBASE, Bioscience Information Service, Science Citation Index and Cochrane Central Register of Controlled Trials) from 2007 to May 2013. Reports published before 2007 were identified from the existing Cochrane review (major databases searched from inception to 2007). The economic model parameters were derived from the clinical effectiveness review, other relevant reviews, routine sources of cost data and clinical experts' advice. REVIEW METHODS: We assessed randomised controlled trials (RCTs) evaluating self-monitoring in people with atrial fibrillation or heart valve disease requiring long-term anticoagulation therapy. CoaguChek((R)) XS and S models (Roche Diagnostics, Basel, Switzerland), INRatio2((R)) PT/INR monitor (Alere Inc., San Diego, CA USA), and ProTime Microcoagulation system((R)) (International Technidyne Corporation, Nexus Dx, Edison, NJ, USA) coagulometers were compared with standard monitoring. Where possible, we combined data from included trials using standard inverse variance methods. Risk of bias assessment was performed using the Cochrane risk of bias tool. A de novo economic model was developed to assess the cost-effectiveness over a 10-year period. RESULTS: We identified 26 RCTs (published in 45 papers) with a total of 8763 participants. CoaguChek was used in 85% of the trials. Primary analyses were based on data from 21 out of 26 trials. Only four trials were at low risk of bias. Major clinical events: self-monitoring was significantly better than standard monitoring in preventing thromboembolic events [relative risk (RR) 0.58, 95% confidence interval (CI) 0.40 to 0.84; p = 0.004]. In people with artificial heart valves (AHVs), self-monitoring almost halved the risk of thromboembolic events (RR 0.56, 95% CI 0.38 to 0.82; p = 0.003) and all-cause mortality (RR 0.54, 95% CI 0.32 to 0.92; p = 0.02). There was greater reduction in thromboembolic events and all-cause mortality through self-management but not through self-testing. Intermediate outcomes: self-testing, but not self-management, showed a modest but significantly higher percentage of time in therapeutic range, compared with standard care (weighted mean difference 4.44, 95% CI 1.71 to 7.18; p = 0.02). Patient-reported outcomes: improvements in patients' quality of life related to self-monitoring were observed in six out of nine trials. High preference rates were reported for self-monitoring (77% to 98% in four trials). Net health and social care costs over 10 years were pound7295 (self-monitoring with INRatio2); pound7324 (standard care monitoring); pound7333 (self-monitoring with CoaguChek XS) and pound8609 (self-monitoring with ProTime). The estimated quality-adjusted life-year (QALY) gain associated with self-monitoring was 0.03. Self-monitoring with INRatio2 or CoaguChek XS was found to have approximately 80% chance of being cost-effective, compared with standard monitoring at a willingness-to-pay threshold of pound20,000 per QALY gained. CONCLUSIONS: Compared with standard monitoring, self-monitoring appears to be safe and effective, especially for people with AHVs. Self-monitoring, and in particular self-management, of anticoagulation status appeared cost-effective when pooled estimates of clinical effectiveness were applied. However, if self-monitoring does not result in significant reductions in thromboembolic events, it is unlikely to be cost-effective, based on a comparison of annual monitoring costs alone. Trials investigating the longer-term outcomes of self-management are needed, as well as direct comparisons of the various point-of-care coagulometers. STUDY REGISTRATION: This study is registered as PROSPERO CRD42013004944. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Expert commentary

The NIHR Health Technology assessment adds to a substantial evidence base that supports self-monitoring and self-management of oral anticoagulation.

This review is supplemented by a recent NIHR-funded study which reported that even with little training people on oral anticoagulation can successfully self-monitor, and even self-manage, in the community. Individual patient data analysis with 12,800 person-years of follow-up has reported that self-monitoring was effective in the long term and across a wide age range of participants.

Therefore the evidence clearly supports the adoption of self-monitoring as part of a co-ordinated anticoagulation pathway that better supports effective strategies to reduce thromboembolic events in high risk individuals.

Professor Carl Heneghan, Professor of Evidence-Based Medicine and Director of CEBM, Nuffield Dept of Primary Care Health Sciences University of Oxford

Author commentary

This systematic review highlights that self-monitoring of anticoagulation appears to be safe and cost-effective. Based on this, National Institute for Health and Care Excellence (NICE) issued a policy guidance recommending CoaguChek® system and INRatio2® PT/INR coagulometers for self-monitoring of anticoagulation therapy. Paucity of evidence for alternative technologies hampered the comparisons according to the type of coagulometers. This uncertainty may impact on decision making as to which device(s) should be adopted in clinical practice. Further research assessing the longer-term outcomes of self-monitoring as well as the comparative effectiveness of various point-of-care coagulometers would be useful.

Pawana Sharma, Research Fellow, Health Services Research Unit, University of Aberdeen