Warfarin “swingers”-patients who frequently fall outside of the therapeutic range (international normalised ratio, INR, 2–3) for optimum warfarin control-are a group likely to benefit from being switched from warfarin to a novel oral anticoagulant, according to Ian Menown, Cardiologist, Craigavon Cardiac Centre, Northern Ireland.
Speaking at the sponsored symposium “Oral anticoagulants enter the Dragons’ Den” at the Heart Rhythm Congress, 2–5 October, Birmingham, UK, Menown said that being out of the therapeutic range was dangerous. “If we manage to achieve control within the therapeutic range, we can obtain excellent benefits with warfarin as observed in randomised trials-albeit with some safety concerns (ie, the risk of bleeding). But if patients are subtherapeutic, the risk of stroke increases rapidly and exponentially. Gladstone et al (Stroke 2009; 40:235–40) found that of patients with known atrial fibrillation who presented with a first stroke and who had been receiving warfarin, 74.2% had a subtherapeutic INR.” In contrast, he added patients with INRs above the therapeutic range showed a steady increase in the risk of major bleeding.
A study by Morgan et al (Thromb Res 2009; 124:37–41) assessed stroke outcomes according to time in therapeutic range while on warfarin. Patients who were in therapeutic range for more than 70% of the time showed the greatest freedom from stroke events. Menown said: “Being in therapeutic range for more than 70% of the time represents excellent warfarin control; this is what you might see in some specialist clinics in the UK with a particular interest in warfarin management and monitoring. If you look at patients who are in the therapeutic range a respectable 61–70% of the time, already we see a marked increase in stroke events. However, patients are not typically considered “swingers” unless their control is even worse eg.
Regarding an alternative to warfarin, Menown said that the ideal agent should be at least as effective as warfarin, have a predictable response, have a wide therapeutic window (to avoid the problem of “swingers”), have a low risk of severe adverse events, have a fixed dose, and a low potential for drug-drug or food-drug interactions. He added: “Food-drug and drug-drug interactions with warfarin are some of the key reasons why we have warfarin swingers. We can predict and cope with drug-drug interactions with warfarin to some degree, but it is much more difficult to manage food-drug interactions.”
Recent studies have shown new oral anticoagulants to be as least as effective as warfarin at reducing stroke and reducing the risk of major bleeding (in some cases, they have been shown to be more effective). They are also known to have a more predictable response and are less susceptible than warfarin to drug-drug and food-drug interactions, obviating the need for regular monitoring.
In a subgroup analysis of the RE-LY study (Wallentin et al. Lancet 2010; 376: 975–83), those who were warfarin swingers obtained particular benefit from the novel anticoagulant dabigatran (Pradaxa, Boehringer Ingelheim, who sponsored the symposium) showing both a reduction in stroke events and the greatest reduction in intra-cranial haemorrhage.