Journal reference: Matchar DB, Jacobson A, Dolor R, et al. Effect of home testing of international normalised ratio on clinical events. N Engl J Med 2010;363:1608-20 ^[1]

Link: http://dx.doi.org/10.1056/NEJMoa1002617

Evidence cookie says...

Home INR self-testing does not appear to improve or worsen strokes, major bleeds or death when compared to high quality practice based management of anticoagulation. There are no compelling health outcome based reasons for patients to purchase a personal point-of-care INR testing device but their use is likely safe in the hands of sensible patients. Note: there are substantial limitations in evidence from this study.  Please see below for more details.

More details:

Article details

Study design:

non-blinded randomised controlled trial

Study aim:

to determine whether home monitoring with a point-of-care international normalised ratio (INR) measuring device improve clinical outcomes

Methods summary:

Data collected at 28 United States Veteran Affairs medical centres with anticoagulation clinics that:

• met certain guidelines for “high quality anticoagulation management”
• and were treating at least 400 patients

Eligible patients:

• either atrial fibrillation
• or mechanical heart valves (or both)
• required long-term warfarin therapy for an indeterminate period
• needed to be competent in performing self-tests using the device (ProTime Microcoagulation System)
  • trained by staff
  • 2-4 weeks of testing
  • formal competency evaluation performed
• randomisation carried out after the eligible patients were trained and deemed competent

INR testing:

• clinic testing:
  • about once a month
  • designated trained staff responsible for patients’ visits and follow up
  • standard local procedure for anticoagulation management
• self testing:
  • about once a week
  • results recorded by means of an “interactive voice-response reporting system with Web-based local monitoring”
  • if INR outside normal range, the system instructed the patient to contact study staff
  • if INR within normal range, the system automatically instructed the patient on dosing and testing frequency.

Follow up visits:

• data collected every three months after randomisation

Primary end point:

• time to first major event (stroke, major bleeding episode, or death)

Secondary end points:

• time within INR target range
• patient satisfaction with anticoagulation
• quality of life

Statistical analysis:

• power calculation performed; 363 patients with primary events would be required to discern a 32% relative reduction in the annual rate of primary events with 90% power

Results summary:

• 2922 eligible patients randomised (this was less than the sample size of 3200 used in the power calculation)
• mean follow up period 3 years (minimum follow up period of 2 years in power calculation)
• 556 patients had a primary end point event (power calculation based on estimate of 363 patients with primary event)
• few dropouts (1%)

Primary end point:

• no statistically significant difference found between the two groups
  • unadjusted hazard ratio (HR) of self-test group: 0.88 (95% confidence interval [CI], 0.75 to 1.04)
  • after adjustment for duration of anticoagulation, mechanical heart valves, age: 0.90 (95% CI, 0.76 to 1.06)

Secondary end points:

• percentage of time during which INR was within the therapeutic range was modestly higher in the self-test group (absolute difference, 3.8%; 95% CI, 2.7 to 5.0%; P < 0.001)
• better patient satisfaction on the rating score but likely of minimal clinical significance

Study conclusion:

As compared with monthly high-quality clinic testing, weekly self-testing did not delay the time to a first stroke, major bleeding episode, or death to the extent suggested by prior studies. These results do not support the superiority of self-testing over clinic testing in reducing the risk of stroke, major bleeding episode, and death among patients taking warfarin therapy.

Participants:

• August 2003 to May 2008
• US Veteran Affairs Medical Centres
• 2922 study patients (80% of those who underwent competency assessment)
• 98% male
• 92% white
• age: 67.0 ± 9.6 years (SD)
  • the patients in the self-testing group were younger than those assigned to clinic-testing group (P=0.047) but only slightly 66.6 ± 9.7 vs 67.4 ± 9.4
• majority with atrial fibrillation (2236) vs mechanical heart valve (684)
• 27% of patients were taking aspirin in addition to warfarin

Methodological weaknesses

• Being an unblinded study, the small (but statistically significant) improvements in patient satisfaction in the self-test group is of questionable clinical significance.
• Participant demographics limits the generalisability of the results:
  • US veterans
  • almost entire cohort were male and white
• Participant selection may have biased results and threatens external validity:
  • eligible participants were those who were deemed “competent” to use the INR testing device by training followed by a testing phase and assessment prior to randomisation
  • they are likely to have done well in both clinic participation and self-testing
  • side-effects, device use non-compliance and user error is likely to be under-estimated compared to the general population
• The level of care in the control arm seemed to be superior to standard anticoagulation management and again, threatens the external validity of the study
• Self-test frequency at home (weekly) may not be realistic (at least, in the Australian setting where there is no subsided funding)

Methodological strengths

• The study had sufficient participants and power to test its hypothesis.

Biases and conflicts of interests

• The first and second authors have received financial assistance or honoraria or sit on advisory board on various pharmaceutical companies and medical devices companies.
• The study was also supported by the Department of Veteran Affairs (United States) that would otherwise also be funding anticoagulation management of veterans.

Clinical relevance to primary health care

This study found that weekly INR self-testing at home with a point-of-care device neither improved or worsened major outcomes compared to monthly INR testing in an anticoagulation clinic (Veteran Affairs medical centres).  There are some substantial limitations to the evidence and care must be taken in generalising to the Australian primary health care setting.

Firstly, the participants were all US veterans, predominately while males, and the recruitment process likely selected participants who were likely to do well in either arm.  Secondly, neither the self-testing group (weekly INR testing) or high quality anticoagulation clinic group received management typical in the Australian context.  Thirdly, the study is only powered to detect a relative risk difference between the two groups of around 25%; there may be a smaller effect that cannot be detected by this trial.

The participants who performed weekly self-testing did manage to stay within the target INR range more often.  In the absence of any observed benefit in reducing the rate of strokes, major bleeds or death, this finding is of unclear clinical significance.

A sensible and cautious take home message for Australian GPs is that INR self-testing by competent patients probably does not result in any substantial clinical benefits or harms for major outcomes when compared to good quality practice based management.  This information may be helpful for those patients who are considering purchasing a personal point-of-care INR testing device for convenience.

Note: this study does not provide any evidence for the use of point-of-care INR devices in the practice setting.

References

1. Matchar DB, Jacobson A, Dolor R, et al. Effect of home testing of international normalised ratio on clinical events. N Engl J Med 2010;363:1608-20