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Pharmacogenetic warfarin dosing shows marginal to no benefit

2 Feb, 14 | by Alistair Lindsay

The inter-individual variation in warfarin dosing requirements and narrow therapeutic index for anticoagulation necessitates a personalized dosing regimen. Variation in dosing requirements are in part explained by genetic polymorphism in CYP (involved in warfarin metabolism) and VKOR (a warfarin target) genes. A dosing strategy informed by these polymorphism may hold promise to improve anticoagulation control. In three large randomized trials of similar design, a sophisticated pharmacogenetic approach to warfarin initiation was compared with standard care. All three studies used the percentage of time in therapeutic range as the primary end-point. None of the studies were powered to assess bleeding complications. A genotype-guided dosing approach failed to demonstrate improvements in anticoagulation control for the two largest studies. In the smallest of the three studies, pharmacogenomic-based dosing resulted in a statistically significant benefit (mean percentage of time in therapeutic 67.4% vs. 60.3%, p<0.001). Given the lack of benefit in the larger trials, and the modest effect size observed in the single trial demonstrating benefit, genotype-guided therapy does not appear justified in current practice. more…

Does warfarin need to be stopped for device insertion?

12 Jun, 13 | by Alistair Lindsay

Over 1.6 million pacing or cardioverter defibrillator (ICD) devices are implanted worldwide annually and up to 1/3 of this cohort have an indication for long-term anticoagulation therapy. Current guidelines suggest discontinuing the oral anticoagulant and initiating bridging therapy with heparin but this strategy is associated with increased costs, a short but high risk period of normal coagulability, and of itself is associated with a pocket haematoma rate of between 20 to 30%. Small case series have suggested that it may be safe to perform surgery without interrupting warfarin treatment but thus far no adequately powered prospective trial has reported on this strategy. more…

Triple therapy post-PCI? WOEST clarifies

22 May, 13 | by Alistair Lindsay

20-30% of patients taking oral anticoagulants also have ischaemic heart disease that requires treatment by percutaneous coronary intervention (PCI), thereby necessitating dual anti-platelet therapy to prevent stent thrombosis. However, the combination of dual anti-platelet therapy (DAP) and anti-coagulants is associated with a high annual risk of fatal and non-fatal bleeding episodes. This study hypothesised that in patients who must continue with oral anti-coagulants, clopidogrel alone would reduce the risk of bleeding – while not increasing the risk of thrombotic events – compared to clopidogrel and aspirin. more…

Atrial Fibrillation: Women at higher stroke risk

4 Jun, 12 | by Alistair Lindsay

Patients with atrial fibrillation (AF) have a risk of stroke that is five times greater than that of the general population.  Moreover, it has previously been described that women with atrial fibrillation have a higher annual rate of stroke than men (3% vs. 1.6%).    The reasons for this remain unclear, although previous studies have suggested that women may be treated with warfarin less frequently than men.  Therefore the aim of this study was to compare the utilisation patterns of warfarin and the risk of subsequent stroke between older men and women with AF. more…

Apixaban shows promise

8 Mar, 11 | by Alistair Lindsay

Warfarin has been the primary treatment to mitigate the increased risk of stroke associated with atrial fibrillation for more than 40 years. However, up to 30% of patients are not suitable candidates for or are unwilling to receive warfarin therapy despite having a high risk of stroke.  A host of new oral agents are now being developed to replace warfarin and in the AVERROES trial, apixaban, a novel factor Xa inhibitor, was tested in patients unsuitable for warfarin therapy and at increased risk of stroke. more…

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