Re: GPAC guidelines: Stroke and atrial fibrillation

The new BC Guideline, Atrial Fibrillation—Diagnosis and Management (one of four new guidelines in the Stroke and Atrial Fibrillation series), states: “Patients for whom anticoagulation is recommended for stroke prevention, warfarin, or NOACs are available options. Existing evidence does not provide a definitive ability to recommend one class of OAC over another.”[1]

It should be remembered that the mean time in therapeutic range (TTR) in the warfarin arms of the industry-sponsored sentinel NOAC noninferiority trials was 60%, with a range of 55% to 64% (RE-LY 64% [dabigatran], Rocket-AF 55% [rivaroxaban], Aristotle 62% [apixaban]).[2-4] 

But warfarin can be managed at a TTR > 75%. To understand what happens to adverse events at TTRs > 75%, see the Table, which references data from the warfarin arms of the SPORTIF III and SPORTIF V trials.[5]

In BC we do not employ the tools needed to achieve a TTR > 75%, simply because they are not funded by our BC health care system. So BC physicians, health care professionals, and patients do not have open access to these resources, including INR point-of-care testing, computerized warfarin-dosing software, and patient self-testing/self-management programs. This is very unfortunate for patients who are suffering unnecessary strokes and hemorrhages as a consequence. It is also very costly for our health care system.

If we adhere to the BC Guideline, as stated in the December 2015 issue of the BCMJ [2015;57:454-455], without changing our INR management system, our BC mean TTR will likely remain at the North American level of 54%.[6] 

But there is a way to change this within our existing system by improving our lab-based warfarin management system. Consider the following process.
1.    Patients attend the lab as usual.
2.    The INR is performed using an INR point-of-care device.
3.    The INR result is entered into a computerized warfarin-dosing system.
4.    The software mathematically calculates:
       a.    The dose of warfarin
       b.    The TTR
       c.    Date of next INR test
5.    The lab personnel ask four safety questions, record the responses, and accept the warfarin dose if the INR is < 1.5 or > 4.0.
6.    A warfarin-dosing calendar is printed and the patient goes home with the calendar after receiving an appointment for their next INR.
7.    If the INR is < 1.5 or > 4.0 (i.e., critical lab value) or there is an adverse event, the physician is immediately called for appropriate treatment advice.
8.    The INR, TTR, and warfarin dose are sent to the physician’s EMR.

In this model, laboratory personnel:
•    Are trained and certified on INR point-of-care testing and operation of the software.  
•    Are recertified annually.
•    Work under the supervision of a clinical pathologist.
•    Work within the constraints of a standardized medical directive and standard operating procedure from the referring physician and clinical pathologist.
•    Are responsible for the quality control on all INR point-of-care testing/equipment and processes, which must meet provincial laboratory accreditation standards.

The software handles all within-range (1.5–4.0) INRs using the computer.[7] 

The fee for a lab INR is $12.07 in BC. The cost of point-of-care testing test strips and software dosing is $7.00 per INR.

The expected TTR in this system is > 75%, based on the results of the CPAMS study,[8] in New Zealand, where pharmacists/pharmacy technicians (instead of lab personnel) performed INR point-of-care testing. Warfarin dosing was performed using a computer-assisted warfarin-dosing software program.  

In Sweden patients attending an outpatient lab that used a similar lab-run system (personal communication with Dr Tomas Lindahl in Linköping, Sweden, January 2015) and a manual algorithm achieved a TTR > 80%.

In Sweden some patients have been taught to test their own INRs (patient self-testing) at the lab, saving the system the labor cost of testing (personal visit with Dr Peter Svensson in Malmö, Sweden, January 2015).

In Germany 200 000 patients tested their own INRs and dose warfarin using a manual algorithm (patient self-management), saving the system the cost of both testing and dosing. The German patient self-management program’s TTR is > 80%.[9,10]

It is very possible to extend the lab model described above to include both patient self-testing and patient self-management models of care.

How well could patient self-management work in Canada? The best source of this information was published in the December 2015 issue of Thrombosis Research by Mary Bauman, nurse practitioner, and her group at the Stollery Children’s Hospital in Edmonton.[11] Their pediatric patient self-management program (KIDCLOT) was studied over 2.7 years. Children and their parents managed warfarin at home and entered INR results online on the program’s computer software. There were 42 patients (average age: 6 years) in the study. The TTR was > 90%. There were no clots, no hemorrhages, and no dosing errors.

The bottom line
BC needs to upgrade its warfarin management system to achieve a mean provincial TTR > 75%. There are multiple models of improved warfarin management in other countries. The model described above is an example of a place to start in BC without the need to create new funding channels. It maintains a high level of quality control and does not require a major change in patient behavior. It is also amenable to expansion to both patient self-testing and patient self-management models. There are other models of care that will work equally well (pharmacist, nurse, nurse practitioner, physician-led models), subject to appropriate funding and training.

BC needs to provide patients with the option of warfarin patient self-management. If Alberta kids can do it, why can’t we?
—Murray Trusler, MD, MBA, FCFP, FRRMS
VP, INR Online Canada Limited (Not for Profit)

References

1.    Government of BC. BC Guidelines: Atrial fibrillation—diagnosis and management. Accessed 15 March 2016. www2.gov.bc.ca/gov/content/health/practitioner-professional-resources/bc-guidelines/atrial-fibrillation.
2.    Connolly SJ, Ezekowitz MD, Yusuf S, et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med 2009;361:1139-1151.
3.    Patel MR, Mahaffey KW, Garg J, et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med 2011;365:883-891.
4.    Granger CB, Alexander JH, McMurray JJ, et al. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med 2011;365:981-992.
5.    White HD, Gruber M, Feyzi J, et al. Comparison of outcomes among patients randomized to warfarin therapy according to anticoagulant control: Results from SPORTIF III and V. Arch Intern Med 2007;167:239-245.
6.    Oldgren J, Healey JS, Ezekowitz, M, et al. Variations in cause and management of atrial fibrillation in a prospective registry of 15 400 emergency department patients in 46 countries. The RE-LY atrial fibrillation registry. Circulation 2014;129:1568-1576.
7.    INR Online. About INR online (video). Accessed 11 April 2016.  http://caweb.inronline.net/index.php/information/about-inr.
8.    Shaw J, Harrison J, Harrison J. Community pharmacist-led anticoagulation management service: Final report. September 2011. The University of Auckland Faculty of Medical and Health Sciences, School of Pharmacy.
9.    Koerfer R, Reiss N, Koertke H, et al. International normalized ratio patient self-management for mechanical valves: Is it safe enough? Curr Opin Cardiol 2009;24:130-135.
10.    Körtke H, Körfer R. International normalized ratio self-management after mechanical heart valve replacement: Is an early start advantageous? Ann Thorac Surg 2001;72:44-48.
11.    Bauman ME, Massicotte MP, Kuhle S, et al. EMPoWARed: Edmonton pediatric warfarin self-management study. Thromb Res 2015;136:887-893.