Abstract 1157: A Multicentre Randomized Trial Comparing Heparin/warfarin Versus Aspirin As Primary Thromboprophylaxis For Two Years After Fontan Procedure In Children
The Fontan procedure often represents definitive palliation for children with single ventricle physiology; thrombosis (TE) is an important complication. No prospective studies have accurately determined the incidence of TE or effectiveness of prophylaxis regimens. We performed a multicentre international randomized trial of anticoagulation after Fontan in children. All pediatric patients having a Fontan or modified Fontan procedure were eligible. Exclusion criteria included other indications for warfarin or contraindications to study drugs. After informed consent, patients were randomized immediately postop to receive via standard protocols either aspirin (ASA, 5mg/kg/day, no heparin phase), or heparin (10 – 20 units/kg/hr until INR >2.0) followed by warfarin (started within 24 hrs of heparin; target INR 2.0–3.0) for 2 years. Primary endpoint (intention to treat analysis) was TE, either intracardiac or embolic (all events adjudicated). At 3 months and 2 yrs after Fontan, a transthoracic and tranesophageal echo were performed as routine screening. Clinically suspected TE’s were objectively documented. Major bleeding and death were primary adverse outcomes. Over 6 years, 242 patients were screened, 209 were eligible, and 111 consented and were randomized (57 to ASA and 54 to heparin/warfarin). Average age was 3.8 years in both study groups. Baseline height, weight, underlying cardiac conditions, comorbidities, previous cardiac interventions, preop hematology and biochemistry were similar. Pre-Fontan TE had occurred for 18% in the ASA group compared to 9% in the heparin/warfarin group. There were two deaths (postop day 7 and 485) in the ASA group unrelated to TE/bleeding. There were 13 TE in the heparin/warfarin group (5 clinical, 8 routine echo) and 12 TE in the ASA group (4 clinical, 8 routine echo). The overall TE rate in the first 2 years after Fontan surgery was 23% despite TE prophylaxis. Cumulative risk of TE events was constant and similar for both groups at 27 months post-Fontan (p= 0.47). Major bleeding occurred in one patient in each group.
Conclusion: There was no significant difference between the ASA and heparin/warfarin groups regarding effectiveness and safety of TE prophylaxis in the first 2 years after Fontan in children.