Timing of vitamin K antagonist re-initiation following intracranial hemorrhage in mechanical heart valves: Systematic review and meta-analysis

• While MHV patients require VKA therapy, timing of re-initiation post-ICH is unclear
• We undertook a meta-analysis to determine the optimal timing of VKA resumption
• 4–7 days post-ICH may be best to reinitiate VKA, but quality of studies was poor
• There is urgent need for prospective, high-quality evidence to guide best practice

BackgroundWhile evidence supports resumption of vitamin K antagonists (VKAs) among mechanical heart valve (MHV) patients presenting with anticoagulant-associated intracranial hemorrhage (ICH), ideal timing of resumption is uncertain.ObjectiveTo determine the optimal timing of VKA re-initiation and its associated clinical outcomes.MethodsWe performed a systematic review and a meta-analysis of studies published from January 1950 to August 2015. We extracted data on the location of initial ICH, use of cranial surgery, presence of atrial fibrillation, MHV type and position, number of MHVs, and timing of VKA resumption. Outcomes including valve thrombosis, thromboembolic events or ICH recurrence were recorded. Meta-regression analysis was conducting with controlling for covariates. We calculated absolute risks, and assessed the effect of anticoagulant resumption timing on ICH recurrence.Results23 case-series and case-reports were identified. Overall ICH recurrence was 13% (95% confidence interval [CI], 7%–25%), while valve thrombosis and ischemic strokes occurred at 7% (95% CI, 3%–17%) and 12% (95% CI, 5%–23%) respectively. A trend towards lower ICH recurrence was observed with delayed VKA resumption (slope estimate − 0.2154, p = 0.10). Recurrence rate ranged from 50% with VKA resumption at 3 days to 0% with resumption at 16 days.ConclusionAmong patients with MHV, there is inadequate data to suggest an optimal timing of VKA re-initiation following an ICH, though delayed restart appears to be protective against recurrence but is associated with higher risk of thrombosis. Our analysis suggests 4–7 days might be an ideal time with least risk of thrombosis or ICH recurrence.