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Risk/benefit balance of alteplase shifts quickly

Alteplase beneficial within 3h of stroke, but treatment risks may rise after 4.5h

OnMedica Staff

Friday, 14 May 2010

Up to 4.5 hours after ischaemic stroke the benefits of initiating thrombolysis with alteplase continue to outweigh the risks associated with treatment. After that time, treatment risks appear to outweigh the benefits, report researchers in The Lancet this week.

Previous research had already shown that initiating intravenous alteplase within 3 hours of ischaemic stroke improved outcomes. Professor Kennedy R. Lees from Glasgow Western Infirmary led an international team of researchers to pool data from eight trials – including 3670 patients – on the effect of time from stroke onset to initiation of intravenous alteplase, on both therapeutic benefit and clinical risk. Ischaemic stroke was diagnosed by symptoms and a brain CT scan.

Their analysis found that treatment with alteplase until 4.5 hours after stroke onset increases the chance of positive outcome, but good clinical recovery becomes rapidly less likely the more time elapses between stroke onset and treatment initiation.

Three months after stroke, patients treated with alteplase within 90 minutes of stroke onset were more than two-and-a-half times more likely to have good clinical recovery than were patients given placebo. Patients given alteplase by 270 minutes post-stroke were only 22% more likely to have a good clinical recovery compared with those given placebo; and delaying alteplase until 270-360 minutes after stroke increased mortality by 49% relative to placebo.

The risk of brain haemorrhage did not increase with time to treatment, so the authors suggest there must be other reasons for early deaths.

“Our analysis showed that the greatest benefit comes from earlier treatment, since net benefit is diminishing and is undetectable in our sample beyond 4.5 hours,” say the team. Even so, alteplase does not result in excellent benefit in most patients – even those treated early – so questions remain. “We need to understand better the factors that prevent alteplase from being effective in individual patients.”

They conclude: “Patients with ischaemic stroke selected by clinical symptoms and CT benefit from intravenous alteplase when treated up to 4.5h. To increase benefit to a maximum, every effort should be taken to shorten delay in initiation of treatment. Beyond 4.5h, risk might outweigh benefit.”

Authors of an accompanying Comment say: “We need to increase the proportion of patients arriving at hospital in the first golden hour after ischaemia onset by better educating the public to recognise stroke warning signs and by activating the emergency medical system early.” Moreover, they conclude, stroke centres should target “the improvement of hospital-response systems to achieve door-to-needle times of less than 60 min” in most alteplase-treated patients.

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