A new era in stroke prevention for atrial fibrillation: comment on “current trial‐associated outcomes with warfarin in prevention of stroke in patients with nonvalvular atrial fibrillation”
Division of General Medicine, Massachusetts General Hospital, Boston (Dr Singer) Archives of internal medicine
(Impact Factor: 17.33).
04/2012; 172(8):631-3. DOI: 10.1001/archinternmed.2012.897
Available from: Pascale Gaussem
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ABSTRACT: As longevity constantly increases, the number of elderly patients (75 years and older) who require anticoagulation likewise rises steadily. Managing elderly patients receiving anticoagulants is challenging because those patients are at high risk of both thrombosis and bleeding. Moreover, older patients are commonly frail: they have substantial chronic co-morbid conditions including renal impairment and frequent acute illnesses and are often polymedicated. There remains a clear need to optimize the use of anticoagulant drugs in these patients, especially at full anticoagulant dose. In the last decade, efforts have been made to better understand the inter-individual variability in the response of elderly patients to traditional anticoagulants including heparin derivatives (unfractionated heparin, low molecular weight heparins and fondaparinux) and vitamin K antagonists. Moreover, their safety profile has been evaluated in different settings in the elderly, assisting in minimizing risks related to their use. Emergence of new oral anticoagulants (dabigatran, rivaroxaban, apixaban), which appear to be much more convenient, is promising. Even though some elderly patients were included in pivotal clinical trials evaluating these new anticoagulants, the safety of these drugs remains uncertain in real life.
Available from: Keith A A Fox
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ABSTRACT: In the ROCKET AF (Rivaroxaban-Once-daily, oral, direct Factor Xa inhibition Compared with vitamin K antagonism for prevention of stroke and Embolism Trial in Atrial Fibrillation) trial, marked regional differences in control of warfarin anticoagulation, measured as the average individual patient time in the therapeutic range (iTTR) of the international normalized ratio (INR), were associated with longer inter-INR test intervals. The standard Rosendaal approach can produce biased low estimates of TTR after an appropriate dose change if the follow-up INR test interval is prolonged. We explored the effect of alternative calculations of TTR that more immediately account for dose changes on regional differences in mean iTTR in the ROCKET AF trial.
We used an INR imputation method that accounts for dose change. We compared group mean iTTR values between our dose change-based method with the standard Rosendaal method and determined that the differences between approaches depended on the balance of dose changes that produced in-range INRs ("corrections") versus INRs that were out of range in the opposite direction ("overshoots"). In ROCKET AF, the overall mean iTTR of 55.2% (Rosendaal) increased up to 3.1% by using the dose change-based approach, depending on assumptions. However, large inter-regional differences in anticoagulation control persisted.
TTR, the standard measure of control of warfarin anticoagulation, depends on imputing daily INR values for the vast majority of follow-up days. Our TTR calculation method may better reflect the impact of warfarin dose changes than the Rosendaal approach. In the ROCKET AF trial, this dose change-based approach led to a modest increase in overall mean iTTR but did not materially affect the large inter-regional differences previously reported.
ClinicalTrials.gov. Unique identifier: NCT00403767.
© 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.
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