“These results have potentially worrying implications for warfarin users with microbleeds in particular,” lead investigator Dr. Caroline E. Lovelock of John Radcliffe Hospital, Oxford, UK, told Reuters Health by e-mail.
But the results “do not allow us to make definite statements about whether or not patients with microbleeds should start warfarin,” she added. “Many patients starting warfarin do so because they are high risk of having a cardioembolic stroke, and this risk might still outweigh the risk of hemorrhage even in the presence of microbleeds.”
In a systematic review of published and unpublished data, Dr. Lovelock and colleagues analyzed rates of microbleeds associated with ICH, stroke, and transient ischemic attacks (TIA), with results stratified by whether or not patients used antithrombotics. They also assessed prospective data to determine the risk of ICH in antithrombotic users with microbleeds.
The pooled data set included 1461 patients with ICH and 3817 stroke or TIA.
In the June issue of Stroke, the researchers report that microbleeds were more frequent in warfarin users with ICH compared to nonusers (odds ratio, 2.7; p < 0.001). There was no excess of microbleeds in warfarin users versus non-users with stroke/TIA.
The authors saw a similar but weaker association in patients taking antiplatelet agents. Microbleeds were more frequent in antiplatelet users versus non-users with ICH (OR, 1.7; p < 0.001), but there was no excess of microbleeds with use of the drugs by patients with stroke or TIA.
In all treatment groups, microbleeds were more frequent in ICH versus stroke/TIA patients. The difference was greater among warfarin and antiplatelet users (ORs, 8.0 and 5.7, respectively) compared to nonantithrombotic users (OR, 2.8; p difference between pooled OR, 0.01).
The pooled prospective data set included 768 patients with stroke or TIA, with a mean follow-up of 27.7 months. Overall, baseline microbleeds significantly increased the risk of a recurrent ICH among all antithrombotic users (OR, 12.1; p < 0.001). Among warfarin users, microbleeds did not significantly increase the risk of recurrent ICH -- but there were only 5 such cases in warfarin users overall.
“We need tighter estimates of the risks of intracerebral hemorrhage on warfarin in people with microbleeds, and in particular we need to know what the risks are for patients with just one or two microbleeds versus many microbleeds,” Dr. Lovelock said.
Even after pooling results of published and unpublished cohorts of patients, there are still very few data on warfarin users, and “more prospective studies of patients with microbleeds are therefore urgently required,” Dr. Lovelock said.