Santosh Murthy

Santosh Murthy

A conversation with Santosh Murthy, MD, MPH, Assistant Professor of Neurology and Neuroscience, Weill Cornell Medicine, about the decision on when to restart anticoagulation after intracranial hemorrhage.

Interviewed by José G. Merino, MD, Associate Professor of Neurology, University of Maryland School of Medicine.

They will be discussing the paper “Restarting Anticoagulant Therapy After Intracranial Hemorrhage: A Systematic Review and Meta-Analysis,” published in the June 2017 issue of Stroke.

Dr. Merino: Can you please summarize the key findings of your study and place them in context of what was already known on the topic?

Dr. Murthy: There is a lack of standardized recommendations regarding the use of anticoagulant therapy after intracerebral hemorrhage (ICH). Our meta-analysis of observational studies suggests that compared with withholding anticoagulation, resumption of anticoagulant therapy after ICH significantly lowers the risk of ischemic stroke and myocardial infarction (MI) with no discernable elevation in the risk of ICH recurrence. While our results help summarize the existing literature and may serve as a guide to clinicians in making informed decisions, randomized clinical trials are needed to determine the true risk-benefit profile of anticoagulation resumption after ICH.

Dr. Merino: The study addresses an important question and one that I am frequently asked about when I cover the stroke service. What are the implications of your findings for clinicians? Do the limitations of the included studies preclude implementation of specific recommendations?

Dr. Murthy: In the absence of randomized clinical trials, we believe the meta-analysis is subject to the inherent limitations and heterogeneity among the observational studies included. We believe there is a strong confounding by indication, in that the decision to reinstate anticoagulant therapy may have been driven by hematoma characteristics such as hematoma volume, location, and presence of intraventricular hemorrhage, which were not available in all studies. These limitations preclude implementation of specific recommendations.

Dr. Merino: How do you think your findings will affect current treatment guidelines?

Dr. Murthy: The 2015 American Heart Association guidelines recommend resumption of anticoagulation after nonlobar ICH in the presence of strong indications (Class IIb, Level of evidence B). While the results of our study suggest a risk-benefit profile in favor of restarting anticoagulant therapy after ICH, given the significant limitations mentioned above and those detailed in the study, we do not anticipate a change in the current treatment guidelines where the decision to initiate therapy is essentially at the discretion of the treating physician.

Dr. Merino: Do you have data that may help guide clinicians about the timing for resuming anticoagulation after ICH?

Dr. Murthy: Unfortunately, our study did not focus on the timing of resumption of anticoagulation after ICH. There is a paucity of published literature on this topic, which preclude recommendations on the timing of resuming anticoagulation after ICH.

Dr. Merino: In your practice, and taking into account the findings of your study, do you use additional imaging information when making decisions about anticoagulant use after ICH?

Dr. Murthy: In our practice, additional neuroimaging is sought to ensure that secondary causes of ICH, such as arteriovenous malformations and venous infarct, are ruled out, in the acute phase of ICH. Furthermore, we opt for brain magnetic resonance imaging (MRI) particularly in cases of lobar intraparenchymal hemorrhages to rule out cerebral amyloid angiopathy as the etiology of ICH, given the high risk of recurrent hemorrhage. We also typically obtain MRI scans when an underlying tumor is suspected. MRI scans, in general, are sought a few days to weeks after ICH.

Dr. Merino: Your analysis was limited to studies of patients with non-traumatic ICH. Do you think that the findings would be different for patients with traumatic ICH?

Dr. Murthy: Unfortunately, our study did not evaluate patients with traumatic ICH; however, similar to non-traumatic ICH, there is a paucity of data on when to restart anticoagulation. Further studies will be necessary to evaluate the risk association with restarting anticoagulation in patients with traumatic ICH.

Dr. Merino: You conclude that an RCT of anticoagulation after ICH is needed. Do you have any thoughts about the feasibility of such a trial (sample size, length of follow-up needed to capture safety and efficacy outcomes, role of imaging for patient selection, etc.)?

Dr. Murthy: There is currently a lot of interest regarding anticoagulation after ICH. In fact, there is a trial underway in the United Kingdom called REstart or STop Antithrombotics Randomized Trial (RESTART). This is a randomized trial of re-initiation of antiplatelet medications versus withholding antiplatelet agents in patients with ICH who were previously on antiplatelet agents. The trial is in the enrollment phase and aims to follow patients over a two-year timeline. To our knowledge, there are no trials underway on resumption of anticoagulant therapy after ICH.

Dr. Merino: What advice do you have for trainees interested in learning more about doing and interpreting meta-analyses?

Dr. Murthy: The most important aspect about a meta-analysis is choosing a clinically important question, one that randomized trials have not comprehensively addressed. The next key factor is to choose study variables carefully in an effort to balance the heterogeneity among studies. Seeking professional statistical help would, therefore, be crucial. Reading and interpreting previously published meta-analyses in the field of interest is perhaps the best way to become acquainted with the intricacies involved in performing a similar study.

Dr. Merino: Thank you very much.