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Published on 22 January 2008

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Positive findings for warfarin in AF patients

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Warfarin prevents systemic embolism in patients with nonvalvular atrial fibrillation (AF) as well as reducing risk of stroke, a study has found.

The meta-analysis of trial data has been published early online in Heart.

Systemic embolism (eg to limbs or viscera) is a significant risk with AF, and although it is well accepted that warfarin reduces the risk of strokes in such patients, it is not clear whether it also reduces other embolic risks.

The authors of the paper aimed to determine whether the results of published warfarin trials showed any beneficial effect on systemic emboli.

They carried out a comprehensive literature search to identify published randomised controlled trials lasting at least three months that studied standard-dose warfarin (INR at least 2) in adult patients with atrial fibrillation or flutter (except post-operative or due to valvular disease).

Controls could be placebo, anti-platelet agents, low-dose warfarin (fixed dose or INR <2), or aspirin plus low-dose warfarin.

Outcomes studied were systemic embolism and major bleeding as defined in each study.

A total of 775 publications were identified initially, of which 22 were potentially relevant. Of these, seven were excluded for various reasons, leaving 15 studies involving 16,058 participants for meta-analysis.

There were 128 systemic embolic events and 317 major bleeding events in the analysis population.

Warfarin was superior to placebo for reducing systemic embolic events in four studies, with a risk reduction of 71% (two vs nine events; OR 0.29; 95% CI 0.08–1.07), but an increased risk of major bleeding (OR 3.01; 95% CI 1.31–6.92).

There were nine studies comparing warfarin with anti-platelet drugs, and in these warfarin was superior to comparator for reduction of systemic embolism (34 vs 71 events; OR 0.50, 95% CI 0.33–0.75), with a similar level of major bleeds (OR 1.07, 95% CI 0.85–1.34).

Five studies compared warfarin with low-dose warfarin or low-dose warfarin plus aspirin, but all these were stopped early due to clear superiority of standard-dose warfarin in the first to be published, and the results available were not conclusive for systemic emboli.

The authors conclude that as well as reducing the risk of stroke in patients with AF, standard-dose warfarin is more effective than either placebo or anti-platelet drugs for prevention of systemic emboli.

It is more likely to cause major bleeding than placebo, but has a similar risk to anti-platelet agents.

They comment that the comparative risk of bleeding to anti-platelet drugs may be underestimated, as much of the data came from a study in which it was compared to dual anti-platelet therapy, for which the risk of bleeding is greater than single-agent therapy.

Heart



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