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Re: MR to select octogenarians for thrombolysis?

Dear Editor

Ringleb and co-authors concluded that the use of magnetic resonance imaging to select octogenarian patients with acute ischaemic stroke for thrombolytic therapy increases safety(1). They dismiss the possibility that this apparent benefit of MR selection may have been due to selection bias since the NIHSS scores were similar in those in whom MRI was applied versus those not(1). However, we have shown that a significant proportion of older patients have relative or absolute contraindications to MR scanning unrelated to the severity of their stroke (2). Hence, in our view, the apparent reduction in intracerebral haemorrhage by the use of MR selection could well be mainly accounted for by the MR patients having less non-stroke co-morbidity and frailty (eg the need for a pacemaker); these non-stroke co-morbidities were not assessed in the paper. Furthermore, overall outcome, in terms of survival or survival free of disability was not significantly better in those selected by MR compared with those selected by CT.

We would also take issue with their description of their own study and the observational studies included in their systematic review as trials. This is misleading, since, in common usage, ‘trial’ is usually restricted to study designs in which a treatment allocation is determined strictly randomly and the next allocation is concealed from the clinician.

We therefore conclude that this paper does not support the argument that patients (of any age) presenting more than 3 hours after stroke onset should be selected by the use of MR DWI/PWI imaging. Furthermore, the DIAS-2 trial, among patients with an acute ischaemic stroke 3-9 hours after stroke onset, selected for the presence of mismatch on MR DWI-PWI, did not provide evidence that thrombolysis (with i.v. desmoteplase) was of net benefit.(3) This result does throw the 'mismatch' concept into some doubt.

Furthermore, immediate access to MR scanning for acute stroke patients is problematic in many non-specialist hospitals admitting patients with stroke, so any requirement for MR pre-selection might exclude many patients from thrombolytic therapy. We should therefore await further randomised evidence (e.g. from the ongoing EPITHET study) on the utility of ‘mismatch’ on MR as a selection criteria for thrombolysis before making recommendations.

In the meantime, we do, however, agree with the concluding sentence of Ringleb’s article which states the only way to obtain reliable evidence on the effects of thrombolytic therapy beyond 3 hours, especially in octogenarians, is to include such patients in IST-3,(4) the only ongoing randomised trial which permits recruitment of patients over 80.

Peter Sandercock, DM
Joanna Wardlaw, MD
Richard Lindley, MD
Stefano Ricci, MD
On behalf of the IST-3 collaborative group

References

(1) Ringleb PA, Schwark C, Kohrmann M, Kulkens S, Juttler E, Hacke W, et al. Thrombolytic therapy for acute ischaemic stroke in octogenarians: selection by magnetic resonance imaging improves safety but does not improve outcome. J Neurol Neurosurg Psychiatry 2007 Jul 1; 78(7):690-3.

(2) Hand PJ, Wardlaw JM, Rowat AM, Haisma JA, Lindley RI, Dennis MS. Magnetic resonance brain imaging in patients with acute stroke: feasibility and patient related difficulties. J Neurol Neurosurg Psychiatry 2005 Nov; 76(11):1525-7.

(3) Hacke W, Furlan A. Results From The Phase III Study Of Desmoteplase In Acute Ischemic Stroke Trial 2 (Dias 2). Cerebrovasc Dis 23 (suppl 2), 54. 2007.