Intracranial hemorrhage and subsequent ischemic stroke in patients with atrial fibrillation: A nationwide cohort study

Abstract: Background:The risk of ischemic stroke/thromboembolic events after an intracranial haemorrhage (ICH) in atrial fibrillation (AF) patients on warfarin treatment is poorly characterised. The aim of this study was to assess the association between the risk of ischaemic stroke/thromboembolic events and ICH. Methods:Linkage of three Danish nationwide administrative registries in the period between 1999-2012 identified AF patients on warfarin treatment. Event rate ratios of stroke/thromboembolic events, major bleeding and all-cause mortality stratified by ICH were calculated, and Cox proportional hazard models were used to compare event rates among ICH survivors. A matched odds ratio (OR) was calculated for ICH occurrences within 0-3 months relative to 3-6 months prior to a stroke/thromboembolic event. A rate ratio of claimed warfarin prescriptions in a 3-month period pre- and post-ICH was also calculated. Results:We studied 58,815 AF patients (median age 72.6 years; 60% male). When compared to the non-ICH group, the ICH group was at increased risk for stroke/SE/TIA [Rate Ratio 3.67 (95% confidence interval [CI], 3.12 to 4.31] and mortality [5.55 (95% CI, 5.20 to 5.92)], but not for major bleeding [1.06 (95% CI, 0.81 to 1.39)]. The matched OR of ICH occurrences prior to a stroke/SE/TIA was 4.33 (95% CI, 2.44 to 8.15). The rate ratio of claimed warfarin prescriptions post and pre-ICH event was 0.28 (95% CI, 0.24 to 0.33). Conclusion:In this large-scale study of AF patients treated with warfarin, first-time ICH was associated with an increased rate of ischaemic stroke/SE/TIA and mortality compared to the non-ICH group. There was a decrease in the warfarin prescription purchase rate post-ICH period compared to pre-ICH, which may partly explain the excess risk.

Background: The risk of ischemic stroke/thromboembolic events after an intracranial haemorrhage (ICH) in atrial fibrillation (AF) patients on warfarin treatment is poorly characterised. The aim of this study was to assess the association between the risk of ischaemic stroke/thromboembolic events and ICH.

Methods: Linkage of three Danish nationwide administrative registries in the period between 1999-2012 identified AF patients on warfarin treatment. Event rate ratios of stroke/thromboembolic events, major bleeding and all-cause mortality stratified by ICH were calculated, and Cox proportional hazard models were used to compare event rates among ICH survivors. A matched odds ratio (OR) was calculated for ICH occurrences within 0-3 months relative to 3-6 months prior to a stroke/thromboembolic event. A rate ratio of claimed warfarin prescriptions in a 3-month period pre- and post-ICH was also calculated.

Results: We studied 58,815 AF patients (median age 72.6 years; 60% male). When compared to the non-ICH group, the ICH group was at increased risk for stroke/SE/TIA [Rate Ratio 3.67 (95% confidence interval [CI], 3.12 to 4.31] and mortality [5.55 (95% CI, 5.20 to 5.92)], but not for major bleeding [1.06 (95% CI, 0.81 to 1.39)]. The matched OR of ICH occurrences prior to a stroke/SE/TIA was 4.33 (95% CI, 2.44 to 8.15). The rate ratio of claimed warfarin prescriptions post and pre-ICH event was 0.28 (95% CI, 0.24 to 0.33).

Conclusion: In this large-scale study of AF patients treated with warfarin, first-time ICH was associated with an increased rate of ischaemic stroke/SE/TIA and mortality compared to the non-ICH group. There was a decrease in the warfarin prescription purchase rate post-ICH period compared to pre-ICH, which may partly explain the excess risk.