Optimising warfarin monitoring – novel approaches

Anticoagulant service in Evolution

CoaguChek XS

Sue Rhodes & Sarah Bond Anti-Coagulant Leads, Great Western Hospital, Swindon

The Great Western Hospital, Swindon, is a large, modern hospital, which opened in 2002, replacing the Princess Margaret. This article will describe how the anti-coagulation clinic also evolved over time, and became the dynamic service we now deliver today. Prior to 1996 the anticoagulant service at the Princess Margaret Hospital, Swindon, Wiltshire was run by two Consultant Haematologists and rotational junior medical staff. In October 1996 a business case for one whole time equivalent Nurse specialist/pharmacist was approved and both a nurse and a pharmacist were appointed to jointly run and improve the anticoagulant service. Our initial job was to reduce the seven week waiting list for patients commencing on oral anticoagulation, and monitor existing anticoagulated patients using a very old dosing

software programme for around 500 patients. When the Health of the Nation report was issued in 2001 there was a significant increase in the number of patients with atrial fibrillation (AF) being referred for formal anticoagulation to prevent stroke. At about the same time we were shown a new device called the “CoaguChek machine” which could take whole or capillary blood to test INR’s giving the result within a few minutes. After a successful pilot, it was decided that we would use the CoaguChek in our new anticoagulant clinic which proved to be very effective. The number of anticoagulated patients has increased over the years, and we now have 3,500 patients on our case load. Therefore, when the CoaguChek XS was introduced for patients who wished to self-test we were proactive, and became the regional training centre for the South West. This increased for a number of years and we were also able to

provide training in the use of the machine for our community phlebotomist to facilitate INR sampling for patients who had poor venous access and would normally require patient transport to attend the clinic. Phlebotomy, by a conventional method was painful and distressing for the patient and often resulted in under filled samples. The CoaguChek machine allowed phlebotomy to be done in the patient’s home, and we were able to dose the patient straight away. This cut down on the cost of postage as the anticoagulant therapy record book could be updated by the community phlebotomist and we still had an electronic copy of the result and dose on our computerised dosing system. We were able to offer a loan scheme as some patients could not afford the meter, which also helped gauge patient suitability. This scheme worked well, which then led onto loaning machines to patients who were going abroad or working away for long periods of time, enabling a remote phone dosing service. We now have a total of 151 patients (out of a total of 3,500 anticoagulated patients, 4.4%) who self-test. For a number of patients there has been a significant improvement in their warfarin control, increasing their % time in range from 59% to 77% (looking at the last 24 test results). Amongst these, patients who self-test are more likely to be taking warfarin for a mechanical valve replacement or following a venous thromboembolic event (VTE.) Of all our self-testing patients, 19% have a mechanical valve replacement (compared to just 5.6% of our total anticoagulant population) and 29% have had a VTE (compared to 18.6%). Patients are less likely to have AF than our general anticoagulated population with 31% of self-testers on warfarin for AF compared to 56.6% of our general anticoagulated population. Patients who are on long-term warfarin will be more likely to invest in a meter. The patients phone in their INR results to the Anticoagulant answering phone. We are then able to post their new dosing advice, but if it is out of range we call back directly. We have a number of patients who have progressed on to self-managing their warfarin. These are all patients who have been on warfarin for a long time and have a very good understanding of the principles of warfarin dose adjustment. In our clinic’s experience the majority of patients enjoy the convenience of being able to test their INRs at home but also want the reassurance of knowing that they are dosing correctly. Therefore we actively support those patients who

want to self-manage, but do not encourage it with all patients. For those who do want to self-manage, we have a process of asking the patient to suggest their own warfarin doses, and, gradually, as their experience and knowledge increases, we allow them to self-manage. However, patients always have to send in their INR results and doses every three months to our clinic and each patient is also given INR parameters (for example INRs below 1.5 or above 4.5) outside which they have to phone for advice. Once a patient has purchased a machine they are encouraged to watch the DVD and practice. If they feel unsure they can call the Roche care line or the anti-coag clinic directly. Additionally, an easy step guide was produced in clinic as a compliment to the user’s manual. Patients state that the main benefits of having their own machine are empowerment and greater quality of life. Many patients have felt they are held hostage to the local surgery if they require frequent INR monitoring and their arms get painful from frequent phlebotomy. There is no need for them to take time off from work or school in the case of children and many patients feel unable to take lengthy holidays as they are unsure of the quality blood testing in other countries. We have many patients in outlying or rural areas; this reduces the amount of time and money spent travelling. There have been several trials that have shown benefits from self- testing compared to conventional management particularly in maintaining a higher time in therapeutic range, as referenced in Heneghan’s “Systematic Review and Meta-analysis of Individual Patient Data,” published in the Lancet in 2011. Conversely, it has been shown that poor control is a major independent risk factor for reduced long-term survival, particularly after valve replacement. Also this greater control of INR’s reduces costs associated with serious bleeds and thrombosis. Self-testing is not suitable for every patient and ideally this should be agreed between the patient, family or carer and their GP. It is also important that a clear protocol is drawn up which determines a range of issues regarding the testing period, reporting procedures and action. To conclude, the changes we have made in our service have served as an improvement in our anti-coagulation clinic; we are able to deliver faster results, better outcomes and increased patient satisfaction, and envisage this growing as more patients take control of their own care.

There is still a place for greater use of warfarin in atrial fibrillation Dr Terry McCormack Whitby Group Practice

With the advent of the Newer Oral Anticoagulants (NOACs) there is now a choice of treatments other than warfarin which are at least equally as effective. At this time we have limited experience of the NOACs and they are more expensive than warfarin. Therefore they must be seen as an addition to warfarin use rather than a replacement. Good warfarin control and effective, user friendly International Normalised Ratio (INR) monitoring services are as important now as ever they were, if not more important.

knew that the average cost of each stroke to the nation was £11,900 initially and some £2,500 each year for the following three years at which point we stop the costings because the average patient has died at that point. The cost of preventing a stroke came to somewhere between £10,000 and £14,000 and therefore it cost less to prevent these terrible events than allow them to happen.

In 2006 we were approached by NHS Heart Improvement via our local Cardiac Network and offered a grant to develop a local Point of Care Testing (POCT) scheme for INR monitoring under the Primary Care National Priority Project. This was part of a national initiative to encourage greater use of warfarin in the prevention of non-valvular atrial fibrillation (AF). We were considered for this because we already offered a level three service and because I had a specific interest in developing cardiovascular prevention services. It had been well established that the use of warfarin in AF reduced the incidence of stroke when used in high risk patients as described using the CHADS2 score. The relative risk reduction (RRR) when using aspirin to prevent a stroke in AF was 22, whilst the RRR for warfarin was 64(1). The number needed to treat (NNT) with warfarin over one year to prevent a single major stroke as a secondary prevention was 12, whilst in primary prevention it was 37 per year(2). Therefore, overall we knew that for every 25 patients in our clinic, that one of those patients was not suffering a major stroke in a year of treatment. We also knew that in the UK there were 16,000 major strokes per year of which 4,300 patients died and 3,500 patients were discharged to residential care. We also

XS Plus Device

In this article I will describe the Whitby Group Practice warfarin clinic, outline the advantages of this service, explain its popularity with staff and patients alike and describe how this has helped us identify which patients will benefit the most from the use of NOACs.

Our previous INR service required the patient to visit the surgery and have a venous sample taken which was sent to our local laboratory. The next day the laboratory would inform us of the result with a dosing suggestion based on the DAWN system. Our nursing staff would then try and contact the patient by telephone and give them a verbal instruction regarding their new warfarin dose and next test. The next test was most commonly within one week. The dosing advice was now being given a day after the test and therefore they had taken the old dose the night before. This system was tedious and time consuming for our nursing staff. Introducing a new patient to the service was not popular and the service did not lend itself to frail elderly or confused patients who were often the people at greatest risk.

The new point of care testing involved using the Roche Diagnostic capillary blood testing with hand held devices. There is evidence of their accuracy and comparable performance to laboratory based testing(3,4). This required investment in the devices and the testing strips, as well as training for our practice nurses, health care assistants (HCAs) and the district nurses. We established standing operating procedures (SOPs) and there was an initial investment in time and money required. Most of this work was for the nurses and HCAs but their carrot was the promise of a less tedious service afterwards. To replace the laboratory based DAWN computer dosing we invested in the INRstar system. We could now offer the patients an immediate test result with a printout of their day by day warfarin dose as well as an appointment for their next test. There was no need for a follow up phone call, their new dose would start on the day of their test and they had clear written instructions. Retesting became less frequent and in many instances only every four or eight weeks time. The average dose would be worked out on the schedule in fractions by INRstar as it could alter the dose in up to 14 stages. The nursing time required was halved; the number of tests reduced and patient satisfaction was recorded in audits showing across the board improvements in terms of convenience. There was also the option for some patients to have their own machine at home and to self monitor, a particular advantage for frequent travellers and system which has been evaluated and found to be effective and safe, as well as convenient(5,6,7). The system was obviously much better for staff and patients alike but two unexpected advantages became apparent later. The first was the reduced reluctance to initiate warfarin in AF patients. We witnessed a year on year increase in the uptake of warfarin use, rising from 124 patients in 2006 to 179 patients in 2010 and we are now at 199 patients. Therefore using the NNT overall figure of 25 patients per year required to prevent a stroke, we have gone from preventing five major strokes per year in 2006 to nearly eight per year in 2012. The other advantage we could not have envisaged was the ability to know exactly which of patients would benefit from the NOACs. When dabigatran was about to be introduced in 2011 our Primary Care Trust (PCT) medicines management team were considering a ban on its use in primary care in view of the likely high costs. My GP colleague Kathryn Griffith in York and I, with others, borrowed the excellent work of Greg Fell, Matt Fay and others in West Yorkshire to produce a North Yorkshire and York PCT wide guidance on the appropriate use of NOACs in primary care(8). This stated that the drugs

could be used if the patient was allergic to warfarin or if their time in therapeutic range (TTR) was less than 60% or INRs in Range (INRR) less than 50% despite six months treatment. The INRstar system could immediately give us the TTRs for all our patients on the system, which is averaged out for their lifetime use of the system. We had one patient who we knew was allergic to warfarin, but still took the drug because he was so afraid of suffering another stroke. We also identified patients who had poor TTRs, 11%, and therefore effectively were not anti-coagulated. We wrote to all of these patients upon licensing of dabigatran to offer then the opportunity to use the new drug. Everyone else we wrote to saying they would remain on warfarin for the foreseeable future as their control was so good. Using the GRASP computer tool we know that we are using warfarin in an excess of 60% of eligible patients, which exceeds the national average, and we are using it in the appropriate at risk groups as judged by CHADS2, which nationally is not the case(9). We can do better in Whitby and we are striving to do so, but nationally we can do much better than we are doing currently. The new QOF AF indicators will hopefully encourage practices to improve their performance. The reduction in strokes should be recognised by Clinical Commissioning Groups (CCGs) as a good reason to include these aims into QIPP. A great way to enable this is for those CCGs to support and invest in POCT in primary care.

1. Lip GY, Lim HS. Atrial fibrillation and stroke prevention. Lancet Neurol 2007;6:981–93 2. NICE Clinical Guidelines CG36. The management of atrial fibrillation. June 2006. 3. Bereznicki L, Jackson S, Peterson G. Accuracy and clinical utility of the CoaguChek XS portable international normalised ratio monitor in a pilot study of homemonitoring. J Clin Pathol 2007; 60: 311-314 4. Torreiro E, Fernandez E, Rodriguez R. Comparative study of accuracy and clinical agreement of the CoaguChek XS portable device versus standard practice in unexperienced patients. Thromb Haemost 2009; 101: 969-974 5. Cromheeke M, Levi M, Colly L. Oral anticoagulation self-management and management by a specialist anticoagulation clinic: a randomized cross-over comparison. Lancet 356 July 8, 2000 6. Christiansen T, Maegaard M, Sorensen H. Self-management versus conventional management of oral anticoagulant therapy. European Journal of Internal Medicine 17 (2006) 260-266 7. Ansell J, Jacobson A, Levy J. Guidelines for implementation of patient self-testing and patient self-management of oral anticoagulation Int Journal of Cardiology 99(2005) 37-45 8. Management of Atrial Fibrillation (AF): transitional guidance for Dabigatran. A letter to all GPs in North Yorkshire and York PCT, 1 July 2011. 9. Guidance on Risk Assessment and Stroke Prevention for Atrial Fibrillation (GRASP-AF). http://www.improvement.nhs.uk/graspaf/

Management of patients with atrial fibrillation with new oral anticoagulants Nicola Harrison-Tiffin, Programme Manager Public Health, NHS Bury

The availability of new oral anticoagulants has put increased focus on the management of patients with atrial fibrillation. Patients with AF are at 5-6 times greater risk of stroke compared to the general population, but anticoagulation remains suboptimal in many; NICE estimate that 46% of patients who are indicated for warfarin or NOAC not presently anticoagulated. The reasons are multiple; variations in the quality of primary care, reluctance by GPs to recommend warfarin, capacity issues within anticoagulation clinics and the reluctance of patients to take warfarin due to concerns with the drug and the inconvenience it can bring. Now more than ever we need to offer patients greater choice and control over their care whilst PCTs/CCGs need also identify cost savings and productivity opportunities wherever possible. Following the recently published NICE technology appraisals for Dabigatran and Rivaroxaban, prescribing of new oral anticoagulants for patients with atrial fibrillation will undoubtedly increase significantly over the coming year and may soon represent a significant cost pressure on CCG prescribing budgets. Whilst NICE have signalled clearly that NOACs should be considered and discussed with patients, we need also be mindful of the yet unknown pitfalls in switching patients from warfarin to a NOAC. Those settled and well controlled on warfarin may well fair better by remaining on warfarin by avoiding

periods of potential under-coagulation during the switching phase and also considering that the patient may experience side effects. In such cases the reasons for requesting a NOAC should be explored, and in some cases where this derives from the inconvenience of attending an anticoagulation clinic, this could well be addressed through warfarin self-monitoring. Patient self-monitoring enables the patient to test their own INR and report to their clinician for dose adjustment. This gives the patient more freedom to travel and avoids the disruption to work and home life that potentially frequent visits to anticoagulant clinics creates. Patient self-management goes a step further, empowering the patient to determine the dose adjustment with the support of dosing charts, and with access to advice if required. A Cochrane review in 2010 which included 18 studies and 4723 subjects, found that both patient self-monitoring and self-management improved outcomes compared to standard therapy; thromboembolic events were halved (RR 0.50, 95% CI 0.36 to 0.69) and in the 16 trials which reported information on mortality, all-cause mortality was reduced by 36% (RR 0.64, 95% CI 0.46 to 0.89). In view of the clear benefits to patients in terms of greater choice, empowerment, freedom and improved outcomes, combined with the potential to reduce costs through savings from anticoagulation monitoring and potentially reducing the number of patients prescribed more costly NOACS, Bury PCT intends to run a pilot self-management service. This will initially operate from one primary care anticoagulation clinic with the aim of evaluating the cost-effectiveness, patient experience and feasibility of extending the programme out across Bury. Patients will be required to complete training and pass an assessment in order to self-manage. Data for the following will be collected: • Percentage of patients offered self-management and reasons for not offering self-management • Take-up rate of self-management and reason for declining self-management • Percentage of patients completing training • Percentage of patients passing the assessment • Percentage of patients continuing to self-manage at 3 months and 6 months. • Time in therapeutic range • Testing frequency and associated costs • Percentage of patients requiring additional advice on dosing and frequency of contact • Patient satisfaction using a questionnaire

• All related clinical events i.e. reported minor and major bleeds, thrombotic events It is recognised that self-monitoring and self-management are not feasible for some patients. Of the trials included in the Cochrane Review, the average proportion of people able and willing to take part in self-monitoring was 32%. Exclusion rates were higher in older populations. Reasons reported were: • Problems with the device • Physical limitations preventing self-testing • Problems with attending the training • Failing the assessment The pilot seeks to provide further information with regards to local barriers to both offering and taking part in selfmonitoring with the aim of where possible overcoming such barriers to improve equity of access. The studies showed that patients who are capable of selfmanagement have fewer thromboembolic events and lower mortality at the expense of no reduction in major haemorrhage events compared with those who self-monitor. The authors of the Cochrane Review hypothesised that patients may deem a major haemorrhage less detrimental than a thrombotic event. Extensive training and clear guidance is therefore required before patients can self-manage. Patients who self-monitor or self-manage tend to test more frequently than those monitored in clinics. Of the ten studies within the Cochrane Review that reported frequency of testing, the ratio of test in the control arms compared to selfmonitoring or self-management ranged from 1.69 to 4.98. It can be likened to self-adjusted insulin dosing which has been practices for many years and will require clear guidelines and monitoring of testing frequency to derive maximum cost-effectiveness. In Bury there are five community anticoagulation clinics led by GPs and one secondary care clinic, with an average of 120 patients at each community clinic and 400 patients at the secondary care clinic. A limited number of patients already self-manage, having self-funded the monitoring equipment which costs in the region of £300 per device. Test strips are provided on prescription and cost £2.75 per test totalling approximately £110 per year. The following algorithm sets out the proposed management pathway. >

Eligibility • Patients well controlled who whould prefer to self-monitor • Patients out of range (any value) who would appear to benefit from PSM (clinician/patient decision)

Pre-PSM INR result Out of range INR 3.5

INR within 1.5-3.5

Training appointment, self monitoring commences 2 x weekly monitoring Halve monitoring

Yes

1 x weekly monitoring

INR 2-3 for four weeks?

INR 2-3 for four weeks?

No

No

Enhanced telephone support & 2 x weekly monitoring

Guide sheet for dose adjustment and telephone support available

Patient selected

INR 2-3 for four weeks?

Yes

No

Gradually reduce to fortnightly monitoring (or maintain at fortnightly)

Continue 2 x weekly monitoring and support. Once consistenty in range gradually reduce monitoring. After 3-6 months if still not well controlled, consider NOAC/No treatment as per CHADS2 score

6-9 months clinic review with calibration

Yes

Time in therapeutic range: 65%: Continue PSM

The patient must complete training and pass an assessment before being able to self-manage. The initial frequency of testing (once weekly or twice weekly) will depend on the INR prior to self-testing commencement. If the patient is far out of range then twice weekly will be required until the patient is consistently in range. (75% of results over four weeks within INR 2-3). Once the patient is consistently in range the frequency of testing can gradually be reduced with the aim of achieving fortnightly testing. After three months the clinician should consider the success of self-monitoring for the patient and decide whether to continue with selfmanagement, offer a NOAC or stop treatment. The decision will depend on the TTR, the CHADS2 score, their reasons for having difficulty staying in range and patient choice. Patients who continue to self-manage should attend the anticoagulation clinic every 6-9 months for review and QC of the monitor. The pilot will run for six months initially, and subject to evaluation will be extended to other community anticoagulation sites in Bury as an important measure to reduce demand on anticoagulation clinics and improve outcomes. i Commissioning for Stroke Prevention in Primary Care – The Role of Atrial Fibrillation, 2009 ii Garcia-Alamino JM, Ward AM, Alonso-Coello P, et al. Self-monitoring and self-management of oral anticoagulation. Cochrane Database Syst Rev. 2010;(4):CD003839.

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