Aspirin before warfarin in Fontan patients: but what about DOACs?

Dr Chantal Attard

Aspirin should be favoured over warfarin as primary long-term thromboprophylaxis after Fontan surgery, an Australian research team has recommended.

As people with the condition live longer the question of risks and benefits of long term anti-thrombotic therapy has come to the fore and has been answered by a multicentre study involving 121 patients enrolled in the Australian and New-Zealand Fontan (ANZ) Registry.

Among patients with at least five years of thromboprophylaxis after Fontan surgery there was no difference in risk of cerebrovascular injury with warfarin when compared to aspirin; and the anticoagulant was associated with a higher risk of bleeding and reduced bone mineral density (BMD).

The study, which involved patients undergoing neuroimaging showed that asymptomatic cerebrovascular injury was common in all Fontan patients, with 6% having symptomatic. Stroke. However 39% had asymptomatic stroke on MRI scans  and almost all patients showed micro-haemorrhage (96%) and white matter injury (86%) regardless of thromboprophylaxis type.

Patients taking warfarin had more episodes of epistaxis compared to those on aspirin (47% vs 24%), and more patients on warfarin stopped their stopped treatment prior to undergoing a medical procedure (49% vs 9%) compared to aspirin.

All patients high rates of heavy menstrual bleeding, bruising, bleeding from minor wounds and after tooth removal, but thromboprophylaxis was only stopped due to bleeding in one patient.

DXA scans showed that patients taking warfarin had reduced BMD than their aspirin counterparts at all measured sites, but rates of clinically significant reduced BMD and fractures were not significantly greater for warfarin over aspirin users.

The study authors, led by Dr Chantal Attard and Professor Paul Monagle of the Murdoch Children’s Research Institute, Melbourne, said that given the need for regular INR monitoring of warfarin, the results suggested that aspirin should be offered as primary long-term thromboprophylaxis after Fontan surgery.

“However, consideration must be given to important clinical features such as cardiac function and lung function, neither of which were investigated in this study,” they wrote.

The researchers noted there was no difference in health-related quality of life between warfarin and aspirin users, though this might be due to the provision of home INR monitoring for many warfarin patients giving them a sense of control over their health.

They added that the high rates of asymptomatic stroke, micro-haemorrhages and white matter injury seen in the study showed there was a need for further imaging studies to identify when these changes occurred and what factors were associated with stroke risk.

“Early detection of cerebrovascular injury may assist with the identification of children at higher risk of neurodevelopmental problems and allow early implementation of interventions to reduce the long-term burden of disease,” they said.

Similarly the results showed there was a need to be vigilant for bone health in post-Fontan patients, with attention paid to BMD screening and use of vitamin D and calcium, the researchers said.

Speaking to the limbic, Dr Attard said the question of whether DOACs would offer advantages over warfarin for thromboprophylaxis would be answered by studies currently in progress. But this should not be taken for granted in the Fontan population because of the presence of artificial surfaces in the form of patches, baffles and conduits.

“Although the emergence of DOACs has proven successful in various populations, the utility of DOACs as thromboprophylaxis post-Fontan is yet to be established,” she said.

“There are currently a number of DOACs being trialed in children post-Fontan including rivaroxaban and apixaban. While we await the trial results, caution must be taken when using DOACs in Fontan patients.”

Dr Attard said recent literature strongly suggested some DOACs may not be adequate for thromboprophylaxis in the populations where artificial surfaces are present. Three independent studies involving dabigatran and rivaroxaban in cardiac patients were prematurely ceased due to an excess of thromboembolic and bleeding events among patients in the DOAC groups, she noted. In these studies, DOACs were trialled against standard of care in the setting of prosthetic valves, Ventricular Assist Device and Transcatheter aortic valve implantation.

“The Fontan population is clearly one where extrapolation from previous trials is of limited or no value, and so we applaud the investigators who are trialling DOACs post-Fontan, and look forward to the results of these studies in due course,” said Dr Attard.

The findings are published in the Journal of Thoracic and Cardiovascular Surgery

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