Intracerebral hemorrhage outcomes in patients using direct oral anticoagulants versus vitamin K antagonists: a meta-analysis

The objective of this paper is to assess the clinical outcomes between non-traumatic intracerebral hemorrhage (ICH) in patients using direct oral anticoagulants (DOAC) versus vitamin K antagonists (VKA) for non-valvular atrial fibrillation. We also evaluated the predictors of the poor post-ICH outcomes.

We have performed pooled meta-analysis to assess long-term clinical outcomes in patients with DOAC-ICH as compared to those with VKA-ICH. A systematic literature search was conducted by searching the full-text English literature in PubMed, EMBASE, and Cochrane databases for observational studies reporting outcomes on interest. MOOSE guidelines were used to collect data till December 31, 2019 and random effects analysis was carried out to account for heterogeneity. For outcomes, risk ratios(RR) and the mean differences were pooled using a random-effects model and weighted mean differences (WMDs), respectively.

Seventeen studies met the inclusion criteria (n = 25,354 patients; DOAC-ICH arms = 5,631; VKA-ICH arm = 19,273). Patients with DOAC-ICH had smaller hematoma volumes (WMD=-9.59; 95%CI=-15.33–3.85; I2 = 68.6%) and reduced mortality rate at discharge (RR = 0.82; 95%CI = 0.71-0.96; I2 = 9.4%). There was no significant difference between the two groups in rate of hematoma expansion (RR = 0.79; 95%CI = 0.56-1.11; I2 = 50.9%), unfavorable functional outcome (Modified Rankin Scale) at discharge (RR = 0.82; 95%CI = 0.56-1.18; I2 = 80.2%), unfavorable outcome at 3-months (RR = 0.77; 95%CI = 0.56-1.06; I2 = 63.9), and mortality at 3-months (RR = 0.90; 95%CI = 0.73-1.10; I2 = 35∙8%). Multivariate meta-regression revealed that the average age of patient population had a significantly negative correlation with (RR=-0.202; p = 0.017) hematoma expansion.

We conclude that use of DOAC is associated with reduced hematoma volume and mortality rate at discharge. Age is a predictor of the poor outcome of hematoma expansion.