Anticoagulation Self-Monitoring Halves Thromboembolic Risk

Susan Jeffrey

December 02, 2011

December 2, 2011 — Results of a meta-analysis show that self-monitoring of oral anticoagulation by patients was superior to usual care in reducing thromboembolic events, with a risk reduction of 49%.

Self-management of anticoagulation, in which patients not only self-tested International Normalized Ratios (INRs) themselves but actually were trained to self-adjust the warfarin dose based on these results, was superior to self-testing alone, in which dose adjustments were made by physicians.

Rates of bleeding and mortality were similar between groups. The most striking reductions in risk were seen in patients younger than 55 years and in those taking anticoagulation because of a mechanical heart valve, the authors note, but there was no safety signal from this approach even among the very elderly.

"It's clear that for younger individuals, those under 55, this is actually going to be reducing the number of thromboembolic events by half, and the same for those who have valve replacement," study coauthor Rafael Perera, DPhil, from the Oxford University Department of Primary Care Health Sciences in the United Kingdom, told Medscape Medical News. "The recommendation for those individuals would be self-management, instead of the actual management by clinician."

Importantly, he added, "this mode of management is also safe, so it could also be recommended to pretty much anyone else outside those groups, as long as they are given the right level of support."

The study, with first author Carl Heneghan, DPhil, also from the Department of Primary Care Health Sciences, Oxford University, on behalf of the Self-Monitoring Trialists' Collaboration, was published online December 1 in the Lancet.

Slow Uptake of Self-Monitoring

Previous work has suggested that self-monitoring is safe and can significantly reduce thromboembolic events, including death, and that patients spend more time with INRs in the relatively narrow therapeutic range than they would without self-monitoring, the authors note. However, the uptake of self-testing and self-monitoring "has remained inconsistent in and between countries, despite good evidence of their effectiveness and guidelines encouraging patients to discuss this option with clinical staff."

This study extends a previous meta-analysis by this group that showed similar results, Dr. Perera noted. This work was part of a larger initiative to investigate the merits of self-monitoring in a range of chronic conditions including diabetes. However, this new report used individual patient data rather than aggregate study results, enabling the researchers to do a more detailed analysis.

"Specifically, we aimed to address several important gaps in the evidence, including obtaining an estimate of the effect of self-monitoring on time to death, first major haemorrhage, and first thromboembolic event," they write. "We also aimed to investigate effects in important subgroups such as the elderly and those with specific disease indications for anticoagulation such as atrial fibrillation."

For this study, they searched randomized self-monitoring trials and approached authors of the trials included for individual patient data. Of 1357 abstracts, they included 11 trials, with a total of 6417 participants and 12,800 person-years of follow-up.

The authors found a significant reduction in thromboembolic events with self-monitoring, but not in major hemorrhagic events or death.

Table 1. Primary Outcomes With Self-Monitoring vs Usual Care

Endpoint Hazard Ratio 95% Confidence Interval
Thromboembolic events 0.51 0.31 - 0.85
Major hemorrhagic events 0.88 0.74 - 1.06
Death 0.82 0.62 - 1.09

"Striking" reductions in thrombotic events were seen particularly for patients younger than 55 years and for those with mechanical heart valves; the reduction did not reach statistical significance among patients with atrial fibrillation.

Table 2. Thrombotic Events With Self-Monitoring vs Usual Care in Subgroups

Subgroup Hazard Ratio 95% Confidence Interval
Patients younger than 55 years 0.33 0.17 - 0.66
Patients with mechanical heart valves 0.52 0.35 - 0.77

Major outcomes in the subgroup of even the very elderly, those older than 85 years, suggested no risk from self-monitoring, the authors note. There was actually a reduction in mortality in this group, but the number was small, at 75 patients.

"Patients who self-tested and adjusted their doses had significantly lower rates of thromboembolic events, which suggests that patients should be given the opportunity, and provided with training, to undertake self-management," the authors conclude.

"However, self-management does not mean that patients are left to fend for themselves: for instance, in one trial, participants had 24-h back-up available," they note, "and good quality control measures are needed."

Cautious Interpretation

In a commentary accompanying the publication, Paul Alexander Kyrle, MD, and Sabine Eichinger, MD, from the Department of Medicine at the Medical University of Vienna, Austria, point out that in this study, self-monitoring was superior to usual care in risk reduction of thromboembolic events, but bleeding rates and mortality were still similar, "a finding that is contrary to that of a recently published meta-analysis of aggregate data, which reported a significant 26% (odds ratio 0.74, 95% CI 0.63 - 0.87) reduction in death among patients who self-monitored."

The results also showed that self-management was better than self-testing, the commentators write. "However, self-monitoring does not provide the same advantage to all patients." The benefit in this study was seen mainly among those younger than 55 years and in those with mechanical heart valves, and did not reach statistical significance in those with atrial fibrillation, the commentators note.

"A possible explanation could be that patients younger than 55 years, especially those with mechanical heart valves, are highly aware of thromboembolic risks and are therefore prepared to manage their medical treatments, including therapy with vitamin K antagonists," they speculate.

They also raise the issue of new agents either on the market or on the horizon that do not require monitoring at all.

"Dabigatran, a thrombin inhibitor, and rivaroxaban, directed against factor Xa, are both at least as safe and effective as vitamin K antagonists in patients with venous thrombosis," they note. "Importantly, dabigatran at a dose of 150 mg twice daily and apixaban, another factor Xa inhibitor, are superior to vitamin K antagonists in patients with atrial fibrillation in terms of reduction of stroke and bleeding, and apixaban is superior in terms of reduction of mortality. To what extent these new agents will replace vitamin K antagonists is, however, unclear."

Use of these agents is restricted in those patients with kidney disease; for example, these drugs have no direct antidote and are expensive, the editorialists note. In addition, there is little difference between patients receiving these agents and those receiving warfarin who spend most of their time in the therapeutic range. Further, the efficacy of these drugs in patients with mechanical heart valves is not as clear as their benefit in atrial fibrillation or venous thrombosis.

"So we agree with Heneghan and colleagues that self-management (rather than self-testing) of treatment with vitamin K antagonists should be offered to patients with mechanical heart valves, especially those younger than 55 years," the editorialists conclude. "However, we do not see a place for self-monitoring in other areas of this treatment except for individual patients for whom access to routine usual anticoagulation care is restricted."

The study was funded by the UK National Institute for Health Research Technology Assessment Program and the UK National Institute for Health Research National School for Primary Care Research. Dr. Perera has disclosed no relevant financial relationships. Disclosures for coauthors appear in the article. Dr. Kyrle and Dr. Eichinger are consultants for Bayer Healthcare (manufacturer of rivaroxaban) and Boehringer Ingelheim (manufacturer of dabigatran) and have received speaker's fees from Bayer Healthcare, Boehringer Ingelheim, and sanofi-aventis. Dr. Kyrle is a consultant for Pfizer (manufacturer of apixaban) and has received speaker's fees from Daiichi Sankyo. Dr. Eichinger has received speaker's fees from Pfizer.

Lancet. Published online November 30, 2011. Abstract, Comment

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