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Increased early stroke risk when starting warfarin

Patients with atrial fibrillation (AF) receiving warfarin may be at an increased risk of stroke during the first 30 days of treatment, possibly due to a transient hypercoagulable state at the start of treatment, according to a large study based on British patients published recently in the European Heart Journal.1

Using the UK Clinical Practice Research Datalink (CPRD), a nested case–control analysis was conducted within a cohort of 70,766 patients with AF between 1993 and 2008. Stroke cases were randomly matched with up to 10 controls on age, sex, date of AF diagnosis, and time since AF diagnosis. Conditional logistic regression was used to estimate adjusted rate ratios (RRs) with 95% confidence intervals (CIs) of stroke associated with current warfarin use classified according to time since initiation of treatment (<30 days, 31–90 days, and >90 days), when compared with non-use.

A total of 5,519 patients experienced a stroke during follow-up. Warfarin was associated with a 71% increased risk of stroke in the first 30 days of use (RR: 1.71, 95% CI: 1.39–2.12), while decreased risks were observed with initiation >30 days before the event (31–90 days: RR: 0.50, 95% CI: 0.34–0.75 and >90 days: RR: 0.55, 95% CI: 0.50–0.61, respectively).

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Dr Laurent Azoulay (Jewish General Hospital, Montreal, Canada)

Speaking to BJC Arrhythmia Watch, co-author Dr Laurent Azoulay (Jewish General Hospital, Montreal, Canada) said: “The CPRD is the world’s largest primary care database. It records important information often absent in administrative databases, such as body mass index and smoking, which are important potential confounders. Thus, the use of the CPRD allowed us to assemble a large cohort of patients with atrial fibrillation, while at the same time have the possibility to adjust the models for potentially important confounders.”

“Warfarin has been on the market for a long time, and numerous studies have assessed its short- and long-term safety. As for the novel oral anticoagulants, they hold promise, but will require the same scrutiny as warfarin in the years to come. Finally, while our study suggests that warfarin may carry an initial risk of stroke, additional studies will be needed to confirm this finding before recommendations (such as measuring biomarkers) can be made to minimise this risk,” Dr Azoulay added.

Limitations of observational studies

In an accompanying editorial, Professor Hans-Christoph Diener (University Hospital Essen, Essen, Germany) says that, although it highlights important lessons regarding warfarin, the analysis “underscores some of the potential limitations associated with observational analyses from large databases in medicine. Any retrospective observational analysis from administrative databases, despite major statistical efforts to avoid bias, by its nature must be biased. The biggest problem in these kinds of analyses is undetected bias often due to unmeasured confounders.”

The authors caution that the study’s observation “may be confounded by the clinical decision to anticoagulate. Often the patients at highest risk are clinically identified and treated, leading to an early hazard compared with the control lack of treatment.”

References

1. Azoulay L, Dell’Aniello S, Simon TA, Renoux C, Suissa S. Initiation of warfarin in patients with atrial fibrillation: early effects on ischaemic strokes. Eur Heart J 2014;35:1881–7. http://dx.doi.org/10.1093/eurheartj/eht499

2. Diener HC, Granger CB, Patel MR. Is there a period of liability with initiation of warfarin in patients with atrial fibrillation? Eur Heart J 2014;35:1834–5. http://dx.doi.org/10.1093/eurheartj/ehu042

Published on: August 5, 2014

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ENDORSED BY

  • ArrhythmiaAlliance
  • Stars
  • Anticoagulation Europe
  • Atrial Fibrillation Association
 

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