The Pharmaceutical Journal
Vol 270 No 7238 p292
1 March 2003

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Promising result for low-dose warfarin

A study of low-dose warfarin treatment has been stopped early because of promising results in patients with recurrent venous thromboembolism.

The group carrying out the trial says that patients suffering clots of unknown origin in their legs or lungs (idiopathic venous thromboembolism) are usually treated for just three to 12 months with full-dose warfarin with a target international normalised ratio (INR) of 2 to 3.

No agent has, so far, been found to have an acceptable risk:benefit ratio for long-term management, they add. But in this trial, after around six months of standard treatment, 508 patients were randomised to receive either placebo or "low intensity" warfarin (target INR 1.5 to 2) long-term.

Patients had been treated for an average of two years when the trial was terminated following an interim analysis. Rates of recurrent venous thromboembolism were reduced from 7.2 to 2.6 per 100 person-years, a risk reduction of 64 per cent. Major haemorrhage occurred in two patients taking placebo and five taking warfarin. However, eight patients in the placebo group died compared with four in the warfarin group. This equated to a 48 per cent reduction in the composite end point of recurrent event, major haemorrhage or death.

The study is due to be published in the 10 April issue of The New England Journal of Medicine but has been published early online because of its therapeutic implications.

Dr Stephan Moll, of the University of North Carolina, one of the study's authors said: "Until now we had to accept that about 20 to 25 per cent of patients would go on and have another blood clot once blood thinners were stopped."

He continued: "We found the later [low intensity warfarin] maintenance dose to be not only safe in that it did not increase the risk of major bleeding but also effective in preventing a recurrence of clots. That means a maintenance dose should become the new standard of care for patients following a first blood clot and the current treatment."

In an accompanying editorial, Dr Andrew Schafer, University of Pennsylvania, Philadelphia, agrees that the new regimen could be used for patients requiring more than three months of anticoagulation after an initial event. But he warns of forthcoming data showing that a low-dose regimen (INR 1.5 to 1.9) was less effective than conventional warfarin (INR 2 to 3). He calls for a three-way trial of conventional, low dose and placebo therapy.