BARCELONA – Patients who have an intracranial hemorrhage while on warfarin for atrial fibrillation are at sharply increased risk for an ischemic stroke during the following year, a period when many of them are off warfarin, according to a Danish national study.
The absolute risk of a first ischemic stroke among survivors of an intracranial hemorrhage (ICH) while on warfarin was roughly 10% within the first month, 20% within 3 months, and 32% at 1 year. These rates exclude strokes that occurred within the first 7 days after an ICH, Dr. Peter B. Nielsen reported at the annual congress of the European Society of Cardiology.
Dr. Peter B. Nielsen
The design of this real-world national registry study doesn’t permit definitive conclusions to be drawn regarding causality. It is telling, however, that the rate of warfarin use among Danish atrial fibrillation (AF) patients in the year after an ICH plunged by 72%; thus, only about one in four of patients who regularly filled warfarin prescriptions up until the time of their ICH did so afterward, according to Dr. Nielsen of Aalborg (Denmark) University.
He reported on 58,815 warfarin-treated Danes with AF with no prior ICH, ischemic stroke, transient ischemic attack, or systemic embolism at baseline who were followed for up to 13 years, during which 1,639 of them were diagnosed with ICH.
During 261,681 person-years of follow-up of the cohort that remained free of ICH, 6,843 patients were diagnosed with a first ischemic stroke, transient ischemic attack, or systemic embolism. Among the group who had an ICH, that rate was 3.67-fold greater.
Moreover, all-cause mortality occurred in 946 patients with an ICH during 2,404 person-years of follow-up, a rate 5.6-fold greater than in those who remained on warfarin and free of ICH.
When the analysis was restricted to only 2 years of follow-up, the event rate ratios became even more dramatic: AF patients with an ICH were at subsequent 5.4- and 11.8-fold greater risks of ischemic stroke and all-cause mortality, respectively, within the next 2 years, compared with those who were free of ICH.
The optimal timing of resumption of warfarin following an ICH is unclear. Various small studies have come up with recommendations ranging from 1 to 30 weeks, Dr. Nielsen noted.
"Caution may lead to undertreatment and increased risk of ischemic stroke and thrombotic events," he noted. "The question now in my mind is, Who, having survived an ICH, can benefit from a return to warfarin or a switch to a novel oral anticoagulant?"
Discussant Dr. Christopher B. Granger, commenting on the Danish study results, said, "I think this is very important information that there’s this extraordinary risk of ischemic stroke in the year after ICH. I don’t think this has been described before. It of course puts us in a tough bind because we don’t know the safety of returning to warfarin use. This raises the issue in my mind of whether there might be a role for a left atrial appendage occlusion device as an option in this population that’s presumably going to be at high risk of recurrent ICH upon resumption of oral anticoagulation," said Dr. Granger, professor of medicine and director of the cardiac care unit at Duke University Medical Center in Durham, N.C.
When it was pointed out that 3 months of oral anticoagulant therapy is required after placement of the Watchman, a left atrial appendage occlusion device, he responded, "Yes, at least the way it has been developed so far – but this might be an opportunity to test an alternative approach."
Dr. Nielsen and Dr. Granger reported having no relevant financial conflicts.