Resumption of anticoagulation in patients who have had an intracranial hemorrhage (ICH) was associated with a lower risk for thromboembolic events, such as stroke and myocardial infarction, with no apparent heightened risk for ICH recurrence, in a new meta-analysis of observational studies including a total of more than 5000 patients.
The review, published online in Stroke on April 17, was conducted by a team led by Santosh Murthy, MD, Weill Cornell Medicine, New York, New York.
The authors explain that anticoagulation therapy is effective in reducing stroke and systemic embolism in patients with atrial fibrillation and mechanical heart valves, but its benefits must be carefully weighed against the increased risk for ICH. Hence, resumption of anticoagulation after ICH poses a clinical conundrum.
They point out that the absence of evidence-based guidelines to address this issue has led to wide variations in restarting anticoagulation after ICH. Premature reinstatement of anticoagulation could potentially increase recurrent ICH risk, whereas an unnecessary delay in restarting anticoagulation could considerably increase a patient's thromboembolic risk. Furthermore, there is no consensus on the timing of anticoagulant reinstitution.
The researchers therefore conducted a meta-analysis of available studies that have looked at this issue.
Through a literature search, they identified eight studies eligible for inclusion in the meta-analysis, with 5306 ICH patients.
Results showed that reinitiation of anticoagulation was associated with a significantly lower risk for thromboembolic complications (pooled relative risk, 0.34; 95% confidence interval [CI], 0.25 - 0.45).
There was no evidence of increased risk for recurrent ICH after reinstatement of anticoagulation therapy, although there was significant heterogeneity among included studies (pooled relative risk, 1.01; 95% CI, 0.58 - 1.77).
The authors caution that this meta-analysis is "subject to the intrinsic flaws from the nonblinded, retrospective observational design of the included studies."
In particular, because of lack of data on baseline hematoma volume, location, and whether the ICH was a first-time bleed or recurrent hemorrhage, these results may have been affected by confounding regarding which patients at higher perceived risk may have been less likely to be restarted on anticoagulation.
The authors say that these factors, in addition to differences in study design and timing of resumption of anticoagulation, "underscore the importance of future randomized trials to determine optimal antithrombotic strategies after ICH."
The researchers point out that almost all studies included in the meta-analysis evaluated anticoagulation with vitamin K antagonists, but the new generation of oral anticoagulants (NOACs) have a significantly lower ICH risk than does warfarin. They also note that emerging data suggest that patients with NOAC-associated ICH have smaller hematomas and better functional outcomes in comparison with warfarin-associated ICH.
They hope these findings will encourage further studies of the risks and benefits of anticoagulation in patients who have had an ICH, they conclude, and "in the absence of randomized clinical trials…may serve as a guide to clinicians in making informed decisions."
Stroke. Published online April 17, 2017. Abstract
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