Kevin O’Connor, MD

Yaghi S, Mistry E, Liberman AL, Giles J, Asad SD, Liu A, Nagy M, Kaushal A, Azher I, Mac Grory B, et al. Anticoagulation Type and Early Recurrence in Cardioembolic Stroke: The IAC Study. Stroke. 2020;51: 2724–2732.

The risk of recurrence is reduced with anticoagulation in patients with an ischemic stroke in the setting of atrial fibrillation, but whether bridging therapy with either heparin or low molecular weight heparin is needed and the choice of oral anticoagulant (warfarin versus direct oral anticoagulant [DOAC]) remains controversial.

This retrospective analysis of pooled data from the IAC (Initiation of Anticoagulation after Cardioembolic) stroke study examined the risk of recurrent ischemic events and delayed symptomatic intracranial hemorrhage (d-sICH) when employing bridging therapy (or not) and when starting warfarin or a DOAC within 90 days of a stroke. Of 2084 patients, 1289 were included in the analysis of benefits and harms of bridging therapy (bridging, n=203; no bridging, n=1086) and 1251 in the analysis of warfarin versus DOAC (warfarin n=389, DOAC n=862). 

Consistent with previous studies, bridging therapy was associated with d-sICH compared to no bridging (4.4% versus 1.0 %, P=0.002). The association remained after adjustment for potential confounders including age, sex, ischemic lesion > 10mL, early hemorrhagic transformation, and oral anticoagulant choice (HR=2.74 [95% CI, 1.01–7.42], P=0.047). There was no association between bridging and recurrent ischemic events (HR 0.85 [95% CI, 0.46-1.57], P=0.611), even after adjustment for potential confounders (HR, 1.23 [95% CI, 0.63-2.40], P=0.551). Specifically, there was no meaningful impact after adjusting for the time to starting bridging (HR, 1.26 [95% CI, 0.62-2.53], P=0.525).

Use of a DOAC rather than warfarin had a lower rate of recurrent ischemic events (5.3% versus 10.0%, P=0.003). In univariate analysis, there was no significant difference between management strategies and the rate of d-sICH (1.2% versus 2.0%, P=0.303). Cox-regression analyses showed a reduced risk of recurrent ischemic events with a DOAC strategy even when accounting for potential confounders (HR, 0.51 [95% CI, 0.29–0.87], P=0.015). Similar analysis for d-sICH showed no significant difference (HR, 0.57 [95% CI, 0.22–1.48], P=0.246).

These data may help guide anticoagulation strategies, but the analysis has limitations. Although the study found that use of a DOAC rather than warfarin was associated with a lower risk of recurrent ischemic events within 90 days of a cardioembolic stroke, it did not assess long-term outcomes. Analysis of pooled data from European and Japanese studies evaluating recurrent acute ischemic stroke with warfarin versus a DOAC over a period of months to years did not show a statistically significant difference (4.2% versus 4.4%, HR, 0.91 [95% CI, 0.70–1.19], P=0.5).1 Although the study shows a possible benefit of DOACs over warfarin when anticoagulating soon after cardioembolic stroke, DOACs have higher costs and contraindications that differ from warfarin.


1. Seiffge DJ, Paciaroni M, Wilson D, Koga M, Macha K, Cappellari M, Schaedelin S, Shakeshaft C, Takagi M, Tsivgoulis G, et al; CROMIS-2, RAF, RAF-DOAC, SAMURAI, NOACISP LONGTERM, Erlangen and Verona Registry Collaborators. Direct oral anticoagulants versus vitamin K antagonists after recent ischemic stroke in patients with atrial fibrillation. Ann Neurol. 2019;85:823–834.