Ivany E, Ritchie LA, Lip GYH, et al. Effectiveness and Safety of Antithrombotic Medication in Patients With Atrial Fibrillation and Intracranial Hemorrhage: Systematic Review and Meta-Analysis. Stroke. 2022 Jul 8:101161STROKEAHA122038752. doi: 10.1161/STROKEAHA.122.038752. (Systematic review)

BACKGROUND: For patients with atrial fibrillation who survive an intracranial hemorrhage (ICrH), the decision to offer oral anticoagulation (OAC) is challenging and necessitates balancing risk of thromboembolic events with risk of recurrent ICrH.

METHODS: This systematic review assesses the effectiveness and safety of OAC and/or antiplatelets in patients with atrial fibrillation with nontraumatic ICrH. Bibliographic databases CENTRAL, MEDLINE, EMBASE, and CINAHL were searched. Articles on adults with atrial fibrillation with spontaneous ICrH (intracerebral, subdural, and subarachnoid), receiving antithrombotic therapy for stroke prevention were eligible for inclusion.

RESULTS: Twenty articles (50 470 participants) included 2 randomized controlled trials (n=304)' 8 observational studies, 8 cohort studies, and 2 studies that meta-analyzed individual-level data from observational studies. OAC therapy was associated with a significant reduction in thromboembolic events (summary relative risk [sRR], 0.51 [95% CI, 0.30-0.86], heterogeneity I2=2%; P=0.39, n=5 studies) and all-cause mortality (sRR, 0.52 [95% CI, 0.38-0.71], heterogeneity I2=0; P=0.44, n=3 studies). OAC therapy was not associated with an increased risk of recurrent ICrH (sRR, 1.44 [95% CI, 0.38-5.46], heterogeneity I2=70%, P=0.02, n=5 studies). Nonvitamin K antagonist OACs were more effective at reducing the risk of thromboembolic events (sRR, 0.65 [95% CI, 0.44-0.97], heterogeneity I2=72%, P=0.03, n=3 studies) and were associated with a lower risk of recurrent ICrH (sRR, 0.52 [95% CI, 0.40-0.67], heterogeneity I2=0%, P=0.43, n=3 studies) than warfarin.

CONCLUSIONS: In nontraumatic ICrH survivors with atrial fibrillation, OAC therapy is associated with a reduced risk of thromboembolic events and all-cause mortality without significantly increasing risk of recurrent ICrH. This finding is primarily based on observational data, and further larger randomized controlled trials are needed to corroborate or refute these findings.

Discipline Area Score
Hemostasis and Thrombosis 6 / 7
Hospital Doctor/Hospitalists 6 / 7
Internal Medicine 6 / 7
Neurology 5 / 7
Cardiology 5 / 7
Comments from MORE raters

Cardiology rater

Inadequate data on which to base a complex medical decision because of selection bias. I await the trials in progress for patient and legal safety. Left atrial appendage exclusion device is a safer alternative.

Hemostasis and Thrombosis rater

Meta-analysis limited by included studies being primarily observational or cohort studies (300 of the 50,000 patients were from 2 RCTs), and combining studies where ICH occurred while on OAC and patients who were OAC-naïve.

Hemostasis and Thrombosis rater

A common question in anticoagulation management is about the decision to restart oral anticoagulation after a potentially life-threatening bleed. These data suggest that restarting anticoagulation reduces the risk for thromboembolic disease in atrial fibrillation without significantly increasing the risk for recurrent bleeding; however, larger studies are needed given the low-quality published evidence available for inclusion in the systematic review and meta-analysis.

Internal Medicine rater

I think the previous RCT data (consistent with this conclusion) is more convincing than all the observational data.

Internal Medicine rater

Mostly observational studies but it suggests benefits of restarting oral anticoagulants after ICH (DOAC better than warfarin ).

Neurology rater

Very difficult to know how reliable these data are given the fact that most of it is observational. Clearly, an area where large-scale randomised evidence is needed to clarify the risk:benefit ratio.

Neurology rater

Although based on observational studies, this metanalysis provides useful insight into a better way to proceed in patients with atrial fibrillation and intracerebral bleeding.
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