BIOGRAPHY
Dr Andrew Butler graduated from Edinburgh University in 1990 and trained in Medicine and Haematology in Edinburgh and Glasgow. After exploratory forays to NZ as an RMO in Invercargill in 1992 and Christchurch in 1999 he took up a permanent position as a haematologist in Christchurch in 2006. He has been Director of the South Island Blood and Marrow Transplant programme since 2011 and is a member of the RACP/RCPA Joint Specialist Advisory Committee on training in Haematology. His clinical interests include evidence-based medicine and anti-coagulant related bleeding.
ABSTRACT Novel Anticoagulants Beyond The Hype: A Real World View Of Starting, Stopping And Reversing
Vitamin K antagonists (VKA) lower levels of vitamin-K dependent coagulation factors and moderate levels of physiological anticoagulants. The anticoagulant effect varies between individuals due to genetic and dietary factors and around a half of all INR fluctuations are unexplained. Direct-acting oral anticoagulants (DOAC) act at a single point in the coagulation pathway and have predictable pharmacokinetics allowing fixed-dosing without monitoring.
Three direct-acting oral anticoagulants (DOAC) are licenced in New Zealand. The most widely used is dabigatran for prevention of stroke in atrial fibrillation (AF) and treatment of venous thrombo-embolism (VTE). The pivotal RE-LY study, published in 2009, compared dabigatran with adjusted-dose warfarin in patients with AF at risk of stroke or systemic embolism. Dabigatran 110mg bd was non-inferior with fewer major bleeds compared to adjusted-dose warfarin. Dabigatran 150mg bd reduced stroke risk compared to warfarin with similar bleeding risk.
The regulatory bodies in the US and Europe took a contrasting approach to approval of dabigatran. The rapid rise of dabigatran prescriptions was mainly driven by the convenience of fixed dosing without monitoring. The absence of a reversal agent for dabigatran was seen as a disadvantage although RE-LY study data did not show an excess of deaths. Post-marketing surveillance in New Zealand showed a high rate of bleeding in vulnerable patients not represented in the RE-LY study such as the elderly and in renal failure.
New Zealand has been innovative in producing clinical tools and laboratory assays to guide clinicians in their practice. Recent publications from the RE-LY study have raised concerns that data on monitoring of dabigatran was withheld from the regulatory authorities and the appropriate place of monitoring is yet to be determined. An antidote to dabigatran, idarucizumab, has recently been approved and together with new laboratory assays will enhance the safety of patients.
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