Warfarin, Not Aspirin, May Aid Asian AF Patients With Prior ICH

Marlene Busko

March 21, 2016

TAIPEI, TAIWAN — In a large cohort of Chinese patients in Taiwan with atrial fibrillation and a prior intracranial hemorrhage (ICH), the number needed to treat to prevent a stroke was lower than the number needed to harm to produce another brain bleed (37 vs 56) among those with a CHA2DS2-VASc score >6 who were treated with warfarin[1].

Patients with a lower CHA2DS2-VASc score did not have this same benefit, "suggesting that warfarin use should be reserved for Chinese AF patients with prior ICH with a CHA2DS2-VASc score >6", Tse-Fan Chao (Taipei Veterans General Hospital, Taipei, Taiwan) and colleagues write, in the study published online March 11, 2016 in Circulation.

Moreover, in this population of 307,640 newly diagnosed adult AF patients in Taiwan, of whom 4.2% had a prior ICH, aspirin increased the risk of recurrent ICH but did not reduce the risk of subsequent ischemic stroke. "Thus, antiplatelet therapy should not be used in AF patients with a past history of ICH for stroke prevention," Chao and colleagues caution.

The analysis was based on data from National Health Insurance Research Database in Taiwan from 1996 to the end of 2011, before novel oral anticoagulants (NOACs) were available there.

Invited to comment, Dr Hugh Calkins (Johns Hopkins Hospital, Baltimore, MD) told heartwire from Medscape that this timely, impressive study has four clear messages:

  • "Prior intracranial hemorrhage puts your risk for subsequent intracranial hemorrhage up fivefold.

  • In this group, aspirin really shouldn't be used as it increases risk without benefit.

  • Coumadin does lower stroke risk; it does increase risk of intracranial hemorrhage.

  • In the Asian population the threshold [to initiate it] seems to be [a CHA2DS2-VASc score of] 6; and NOACs likely will provide a superior alternative to anticoagulation with warfarin, because it's been well established that they are better to reduce the risk of intracranial hemorrhage."

Preventing Stroke in Patients With Prior Brain Bleed

The appropriate treatment strategy to prevent stroke using oral anticoagulants remains unclear in patients with AF and a prior brain bleed, Chao and colleagues write.

Asian patients have a higher prevalence of ICH than non-Asians, and concerns about ICH could lead some physicians to withhold oral anticoagulants for some AF patients. And although several NOACs have been shown to be at least as effective as warfarin in preventing stroke in AF patients, albeit with a much lower risk of ICH, AF patients with prior ICH were excluded from these trials.

Thus, they performed a nationwide cohort study to assess the risk of ischemic stroke and ICH with different treatments.

They identified 12,917 patients aged 20 and older with AF, a CHA2DS2-VASc score >2, and prior ICH (subarachnoid hemorrhage in 12.3%, intracerebral hemorrhage in 68.6%, epidural hemorrhage in 2.5%, subdural hemorrhage in 12.6%, and nonspecified type in 4.0%). On average, the ICH had occurred 3.3 years prior to the diagnosis of AF.

The patients were divided into three treatment groups: no treatment (63.6%), antiplatelet therapy (27.5%), and warfarin (8.9%).

During a mean follow-up of 3.3 years, there were 3857 (2.4%) ICH events and 21,017 (13.3%) ischemic-stroke events.

The risk of further ICH was fivefold higher in nontreated AF patients with a past history of ICH, compared with those without ICH (4.2% vs 0.6% per year).

Among patients with a history of ICH, the annual rate of ischemic stroke was 3.4% among warfarin users and 5.2% among antiplatelet users, and the annual rate of ICH was 5.9% among warfarin users and 5.9% among antiplatelet users.

Based on an analysis of recent studies of NOACs, Chao and colleagues estimate the risk of ICH for AF patients with prior ICH can be reduced from 5.9% with warfarin to around 2.8% and even as low as 1.9% when NOACs are used. Based on this assumption, initiating oral anticoagulants with a NOAC could be lowered to a CHA2DS2-VASc score of 2 (annual risk of ischemic stroke 3.2%). "Whether the use of NOACs could lower the threshold for treatment deserves further study," they conclude.

Moreover, in addition to oral anticoagulants, devices that occlude the left atrial appendage may represent an alternative approach to try to prevent stroke, mainly in patients with an absolute contraindication to oral anticoagulation because of a very high bleeding risk, they note, but head-to-head-comparisons are not available.

"We really need more data," Calkins agrees. "Now we have more options. We know aspirin's out. We have Coumadin, we have all the different NOACs, we have Watchman. . . . This would definitely be a group of patients where Watchman would be indicated and paid for," but currently, with no comparative data, clinicians are left struggling to determine the best option for a particular patient.

Chao and the other coauthors have reported they have no relevant financial relationships. Calkins has consulted for Boehringer Ingelheim, AtriCure, and Daiichi-Sankyo.

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