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Alessandro Biffi, MD
Dr. Biffi examines the resumption of anticoagulation therapy after intracerebral hemorrhage.
Alessandro Biffi, MD
“This is one of the most vexing issues in vascular neurology nowadays, because we know [that] … patients in atrial fibrillation are at exceedingly high risk for one or more strokes, especially recurrent strokes,” said Mark J. Alberts, MD, Chief of Neurology at Hartford Hospital in Connecticut. Dr. Alberts did not participate in the study.
Although ICH location (ie, lobar vs nonlobar) provides information about etiology and the risk of ICH recurrence, previous studies have not examined the effect of ICH location on oral anticoagulation resumption. Previous studies also have not examined functional outcome following resumption of oral anticoagulation after ICH.
Meta-Analysis Included Three Trials
To address these questions, Dr. Biffi and colleagues conducted a meta-analysis of patient data from three studies of ICH. The studies were a German investigation that included 542 patients, an American investigation of 268 patients, and another American study of 217 patients. Eligible participants were 18 or older, had a diagnosis of acute ICH confirmed by CT, and were taking oral anticoagulants to prevent cardioembolic stroke resulting from nonvalvular atrial fibrillation. Patients with a history of prior ICH were excluded.
Dr. Biffi and colleagues assessed whether, at one year after ICH, resumption of oral anticoagulation was associated with mortality, favorable functional outcome (defined as modified Rankin Scale [mRS] score of 0 to 3), or recurrent ICH and ischemic stroke. They used multivariable Cox regression models to analyze nonlobar and lobar ICH cases separately.
Anticoagulation Resumption Reduced Mortality
In all, 641 patients had nonlobar ICH at baseline, and 386 participants had lobar ICH. Among patients with nonlobar ICH, 179 (28%) resumed oral anticoagulation therapy. Eighty-eight (23%) of patients with lobar ICH resumed anticoagulation therapy. ICH volume and CHADS2 and HAS-BLED scores were not associated with oral anticoagulation resumption in either lobar or nonlobar ICH. Discharge mRS was associated with oral anticoagulation resumption in lobar ICH only.
In multivariable analyses, resumption of oral anticoagulation after nonlobar ICH was associated with decreased mortality (hazard ratio [HR], 0.22) and improved functional outcome (HR, 5.12) at one year. Oral anticoagulation resumption after lobar ICH was associated with decreased mortality (HR, 0.25) and favorable functional outcome (HR, 4.89).
One limitation of the meta-analysis is that it examined observational studies, which are susceptible to ascertainment bias. “Physicians are going to do what they think is in the best interest of the patients, so you have bias in terms of who gets started and does not get started [on oral anticoagulation therapy],” said Dr. Alberts. Another limitation is that few patients in the meta-analysis used a new oral anticoagulant.
Many variables influence the decision about whether a patient should resume oral anticoagulation, including the severity of the initial stroke, the patient’s risk profile, and the size of the patient’s left atrium. “We need data from prospective randomized trials to figure out what the best approach is,” Dr. Alberts concluded.
Dr. Biffi’s meta-analysis was funded by a grant from the NIH.
—Erik Greb
Suggested Reading
Goldstein JN, Greenberg SM. Should anticoagulation be resumed after intracerebral hemorrhage? Cleve Clin J Med. 2010;77(11):791-799.
Nielsen PB, Larsen TB, Skjøth F, Lip GY. Outcomes associated with resuming warfarin treatment after hemorrhagic stroke or traumatic intracranial hemorrhage in patients with atrial fibrillation. JAMA Intern Med. 2017 Feb 20 [Epub ahead of print].
Poli D, Antonucci E, Dentali F, et al. Recurrence of ICH after resumption of anticoagulation with VK antagonists: CHIRONE study. Neurology. 2014;82(12):1020-1026.