Anticoagulation self-monitoring halves thromboembolic risk

Susan Jeffrey

December 02, 2011

Oxford, UK - 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% [1].

Self-management of anticoagulation, where patients not only self-test international normalized ratios (INR) themselves but actually were trained to self-adjust the warfarin dose based on these results, was superior to self-testing alone, where 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 Dr Rafael Perera (Oxford University, UK) said in an interview. "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 Dr Carl Heneghan (Oxford University), was published online December 1, 2011 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 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 [2], Perera noted, 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 them 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 hemorrhage, 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 6417 participants and 12 800 person-years of follow-up.

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

Primary outcomes with self-monitoring vs usual care


End point
Hazard r atio
95% C I
Thromboembolic e vents
0.51
0.31-0.85
Major h emorrhagic e vents
0.88
0.74-1.06
D eath
0.82
0.62-1.09

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

Thrombotic events with self-monitoring vs usual care in subgroups


Subgroup
Hazard r atio
95% C I
Patients < 55 y
0.33
0.17-0.66
Patients with m echanic al h eart v alves
0.52
0.35-0.77

Major outcomes in the subgroup of even the very elderly, over 85 years of age, suggested no risk from self-monitoring, they 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 the training to undertake self-management," the authors conclude.

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

Cautious interpretation

In a Commentary accompanying the paper [3], DrsPaul Alexander Kyrle and Sabine Eichinger (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 26% reduction (odds ratio 0.74, 95% CI 0.63-0.87) in death among patients who self-monitored" [4].

The results also showed self-management was better than self-testing, they 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, they 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 don't require monitoring at all.

"Dabigatran [Pradaxa, Boehringer Ingelheim], a thrombin inhibitor, and rivaroxaban [Xarelto, Bayer/Johnson & Johnson], 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 [Eliquis, Bristol-Myers Squibb/Pfizer], 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 with kidney disease, for example; they have no direct antidote, and they are expensive, the editorialists note. In addition, there is little difference between these agents and those on warfarin who spend most of their time in the therapeutic range, and their efficacy 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," they 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 th e UK National Institute for Health Research (NIHR) Technology Assessment Program and the UK NIHR National School for Primary Care Research . No conflicts of interest are listed for Perera; d isclosures for the coauthors are listed in the paper. Kyrle and Eichinger are consultants for Bayer Healthcare and Boehringer Ingelheim and have received speaker ' s fees from Bayer Healthcare, Boehringer Ingelheim, and Sanofi-Aventis. Kyrle is a consultan t for P fizer and has received speaker ' s fees from Daiichi Sankyo. Eichinger has received speaker ' s fees from Pfizer .

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