Ischaemic stroke on anticoagulation therapy and early recurrence in acute cardioembolic stroke: the IAC study

Abstract

Background and purposeA subset of ischaemic stroke patients with atrial fibrillation (AF) have ischaemic stroke despite anticoagulation. We sought to determine the association between prestroke anticoagulant therapy and recurrent ischaemic events and symptomatic intracranial haemorrhage (sICH).MethodsWe included consecutive patients with acute ischaemic stroke and AF from the Initiation of Anticoagulation after Cardioembolic stroke (IAC) study from eight comprehensive stroke centres in the USA. We compared recurrent ischaemic events and delayed sICH risk using adjusted Cox regression analyses between patients who were prescribed anticoagulation (ACp) versus patients who were naïve to anticoagulation therapy prior to the ischaemic stroke (anticoagulation naïve).ResultsAmong 2084 patients in IAC, 1518 had prior anticoagulation status recorded and were followed for 90 days. In adjusted Cox hazard models, ACp was associated with some evidence of a higher risk higher risk of 90-day recurrent ischaemic events only in the fully adjusted model (adjusted HR 1.50, 95% CI 0.99 to 2.28, p=0.058) but not increased risk of 90-day sICH (adjusted HR 1.08, 95% CI 0.46 to 2.51, p=0.862). In addition, switching anticoagulation class was not associated with reduced risk of recurrent ischaemic events (adjusted HR 0.41, 95% CI 0.12 to 1.33, p=0.136) nor sICH (adjusted HR 1.47, 95% CI 0.29 to 7.50, p=0.641).ConclusionAF patients with ischaemic stroke despite anticoagulation may have higher recurrent ischaemic event risk compared with anticoagulation-naïve patients. This suggests differing underlying pathomechanisms requiring different stroke prevention measures and identifying these mechanisms may improve secondary prevention strategies.

Aetiology, secondary prevention strategies and outcomes of ischaemic stroke despite oral anticoagulant therapy in patients with atrial fibrillation

“…Due to this development, the number of patients with AF suffering a stroke despite anticoagulation is expected to increase, too 6 7. Accumulating evidence suggests that patients with AF and stroke despite anticoagulation are at a higher risk for future recurrence than patients who were naive to anticoagulation treatment before stroke 8–10…”

“…For stroke physicians, ischaemic stroke despite anticoagulation in patients with AF represents a challenge in everyday clinical practice, as its aetiology is not well-understood 11. Competing stroke mechanisms such as large artery and small vessel disease, as well as non-adherence or inappropriately dosed anticoagulation have been discussed as potential causes of stroke despite anticoagulation,8–11 but few data on their relative frequency exist 6. A better understanding of the aetiology of stroke despite anticoagulation is needed to inform strategies to prevent recurrence after a stroke despite anticoagulation 11.…”

Treatment standards for direct oral anticoagulants in patients with acute ischemic stroke and non-valvular atrial fibrillation: A survey among German stroke units

“…Seiffge et al could not find a beneficial effect of DOAC switching in their large meta-analysis, but this could be due to limitations in the external validity of the underlying original data regarding this specific topic [ 6 ]. Even after adjusting for pertinent confounders, the recent IAC study found no evidence of a beneficial effect [ 26 ]. Rather, AIS despite OAC appears to be an independent risk factor for future events that is poorly controlled by any OAC continuation alone [ 27 ].…”

Ischemic Stroke of Suspected Cardioembolic Origin Despite Anticoagulation: Does Thrombus Analysis Help to Clarify Etiology?

“…However, despite sufficient medication, some patients suffer from cerebral ischemic strokes of the suspected cardioembolic origin ( 4 ). These patients are at higher risk for further stroke recurrence ( 4 , 5 ), which illustrates the importance of a better pathophysiologic understanding of these ischemic events despite therapy, as reasons for that are not clarified yet. Phenomena, such as non-adherence to medication, genetic predisposition regarding drug effectiveness, or lastly another underlying stroke cause than the suspected cardioembolic origin have been discussed ( 4 , 6 , 7 ).…”

“…With regard to an increased risk of stroke recurrence after an ischemic event despite anticoagulation for a suspected cardioembolic source ( 4 , 5 ), the important question remains which is the appropriate secondary prophylaxis for those patients. In the present study, the histologic and imaging characteristics of thrombi from patients with an acute ischemic stroke despite anticoagulation for treatment of a suspected cardioembolic source were analyzed and compared with suspected cardioembolic strokes without anticoagulation as well as patients with non-cardioembolic stroke.…”