Rapid Reversal of Anticoagulation Reduces Mortality from Intracerebral Hemorrhage

By Matthew Fink, MD

Louis and Gertrude Feil Professor in Clinical Neurology and Chair, Department of Neurology, Weill Cornell Medical College

SOURCE: Sheth KN, Solomon N, Alhanti B, et al. Time to anticoagulation reversal and outcomes after intracerebral hemorrhage. JAMA Neurol 2024;81:363-372.

Intracerebral hemorrhage (ICH) is the deadliest type of stroke. ICH associated with anticoagulation carries an even higher mortality. Serial imaging studies have
demonstrated that there is significant hematoma enlargement during the first few hours after arrival at the hospital, and this also portends a poor outcome.

It is standard procedure to administer agents that will reverse the effects of anticoagulation. In those patients who are treated with a vitamin K antagonist, standard treatment is fresh frozen plasma (FFP), prothrombin complex concentrate (PCC), and vitamin K. For patients treated with direct thrombin inhibitors or factor Xa inhibitors, FFP and PCC have been used frequently, but there are specific agents that have been developed to reverse the new oral agents. This issue is becoming more important as the prevalence of atrial fibrillation continues to rise, resulting in larger numbers of older patients being treated with anticoagulant medications. We expect that the number of patients presenting to hospitals with anticoagulant-associated ICH will continue to increase for the foreseeable future.

Because the numbers of patients with primary ICH are far lower than those with ischemic stroke, it has been difficult to accumulate a large enough number of patients to clearly analyze the relationship between the time of the hemorrhage and the time to treatment. We need to answer the important question: Does rapid treatment result in a better outcome?

The investigators queried the nationwide Get With The Guidelines Stroke Registry of the American Heart Association to determine door-to-treatment times for reversal of anticoagulation and outcomes in patients with anticoagulation-associated ICH.

The investigators analyzed data from 465 hospitals across the United States from 2015 to 2021 for patients who presented with ICH within 24 hours of symptom onset. They identified those who had anticoagulation-associated ICH and analyzed door-to-treatment times and outcomes using logistic regression modeling and adjusting for demographics and history. The primary outcome was composite inpatient mortality and discharge to hospice. Additional secondary outcomes included functional outcome as determined by the modified Rankin Scale score at the time of hospital discharge, ambulatory status of the patient, and where the patient was discharged after hospitalization.

They identified 9,492 patients with ICH, of whom 7,469 had documented reversal of anticoagulation. Of these, 44.6% were female and the median age was 77 years. A total of 4,616 of 5,429 patients taking warfarin received reversal therapy (85%) and 2,856 of 4,069 taking non-vitamin K oral anticoagulants (70.2%) received reversal therapy. There was information about time to treatment for 5,224 patients, and the median onset-to-treatment time was 232 (range 142-482) minutes and the median door-to-treatment time was 82 (range 58-117) minutes. A door-to-treatment time of 60 minutes or less was documented in 1,449 patients (27.7%). Treatment time of less than 60 minutes was associated with a decreased mortality and transfer to hospice (odds ratio, 0.82), but there was no difference in functional outcome at the time of discharge. The patients who were treated within 60 minutes or less tended to be of white race, to have a higher blood pressure on arrival, and to have a lower stroke severity.

This observational data taken from a large and reliable database of U.S. hospitals suggests an improved survival for patients with anticoagulation-associated ICH if they received reversal therapy within or less than 60 minutes. Additional study will be needed to confirm these findings, but these data alone should be enough for clinicians to increase their vigilance and move as quickly as possible to reverse anticoagulation in patients who present with ICH. Systems of care should analyze any delays associated with hospital transfers as well as the availability and preparation of reversal agents by hospital pharmacies.