LOS ANGELES – When a patient with atrial fibrillation (AFib) has a cardioembolic stroke, the best blood thinner to start may be a direct-acting oral anticoagulant (DOAC), possibly beginning 7-10 days after the index stroke, according to an analysis of 90-day, observational outcomes data from nearly 1,300 patients.
Mitchel L. Zoler/MDedge News
Dr. Shadi Yaghi
The analysis also suggested that the use of “bridging” anticoagulant treatment by injection before a patient with atrial fibrillation (AFib) starts a daily oral anticoagulant regimen following a cardioembolic stroke is not a good idea. Patients who received bridging anticoagulation had a nearly threefold higher rate of symptomatic intracranial hemorrhage than did patients who did not, and their bridging treatment failed to protect them from recurrent ischemic events, Shadi Yaghi, MD, said at the International Stroke Conference, sponsored by the American Heart Association. The bridging regimens delivered either heparin or low-molecular-weight heparin.
Based on the findings, “it seems reasonable to avoid bridging unless absolutely necessary, to initiate a DOAC unless it’s contraindicated, and to start the DOAC on day 7-10 following the stroke in most patients,” said Dr. Yaghi, a vascular neurologist and director of stroke research at NYU Langone Health in New York.
“It’s been hard to develop a broad guideline on when to start oral anticoagulation” after a cardioembolic stroke in AFib patients. The best time “depends on a lot of variables and how the patient responded to acute treatment,” commented Alexis Simpkins, MD, a vascular and stroke neurologist at the University of Florida in Gainesville. “You want to start treatment before the patient has another stroke, but not so soon that the treatment causes symptomatic hemorrhagic transformation.”
Dr. Yaghi’s suggestion, based on his findings, to start treatment for most patients with a DOAC 7-10 days after their index stroke “shows consistency” with the prevailing guideline recommendation from the AHA/American Stroke Association to start oral anticoagulation in this patient population 4-14 days after the index stroke (Stroke. 2018 March;49[3]:e46-e99), she noted.
Dr. Alexis Simpkins
A recent article reviewed the uncertainty about the best time to start oral anticoagulation in AFib patients after a cardioembolic stroke and the subtle differences that distinguish various international medical groups that, like the ASA, have made recommendations (Lancet Neurol. 2019 Jan 1;18[1]:117-26). According to this review, a major limitation of these various recommendations has been the lack of actual evidence collected from AFib patients who began receiving a DOAC shortly after a cardioembolic stroke, although the article added that several studies in progress are collecting these data.
The study reported by Dr. Yaghi pooled data collected from 2,084 recent AFib patients with a cardioembolic stroke treated at any of eight comprehensive U.S. stroke centers. They excluded patients who died from causes unrelated to the primary endpoint, those who did not receive an anticoagulant or had incomplete data, and patients lost to follow-up, leaving 1,289 evaluable patients. During their 90-day follow-up, 10% of the patients had an ischemic event, a symptomatic intracranial hemorrhage, or an extracranial hemorrhage.
The study’s primary analysis showed no statistically significant difference in the incidence of recurrent ischemic events, symptomatic intracranial hemorrhage, or both based on when oral anticoagulant treatment began: 0-3 days, 4-14 days, or more than 14 days after the index stroke.
The investigators then subdivided patients into the subgroup that started treatment with a DOAC and the subgroup that started treatment with warfarin and also further subdivided the 4-14 day time window for starting treatment. Results of this analysis showed that patients who received a DOAC and began this treatment 7-10 days after their stroke had a 50% cut in their 90-day events compared with other patients, a difference that fell just short of statistical significance at P = .07. All the other combinations of oral anticoagulant and time of treatment initiation analyzed showed neutral effects that never came near statistical significance.
Secondary data analyses also showed that both patients with a history of a stroke prior to their index stroke and patients with ipsilateral atherosclerosis came close to having a statistically significant increased rate of a subsequent ischemic event during 90-day follow-up. Furthermore, women, patients with a history of hyperlipidemia, and patients who developed hemorrhagic transformation of their index stroke all had significantly increased rates of developing a symptomatic intracranial hemorrhage during 90-day follow-up. When the endpoint was limited to recurrent ischemic events only, patients who received a DOAC were 50% less likely to have an event than were patients treated with warfarin, a statistically significant difference.
Although starting a DOAC 7-10 days after the index stroke seems reasonable based on this analysis, the question needs a prospective, randomized study to create an appropriate evidence base, Dr. Yaghi said.
Dr. Yaghi disclosed a financial relationship with Medtronic. Dr. Simpkins had no disclosures.
SOURCE: Yaghi S et al. Stroke. 2020 Feb;51(suppl 1):A119.