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(Stroke. 2008;39:3316.)
© 2008 American Heart Association, Inc.

Original Contributions

Multivariable Analysis of Outcome Predictors and Adjustment of Main Outcome Results to Baseline Data Profile in Randomized Controlled Trials

Safe Implementation of Thrombolysis in Stroke-MOnitoring STudy (SITS-MOST)

Nils Wahlgren, MD, PhD; Niaz Ahmed, MD, PhD; Niclas Eriksson, MSc; Franz Aichner, MD; Erich Bluhmki, PhD; Antoni Dávalos, MD, PhD; Terttu Erilä, MD, PhD; Gary A. Ford, FRCP; Martin Grond, MD; Werner Hacke, MD, PhD; Michael G. Hennerici, MD, PhD; Markku Kaste, MD, PhD, FAHA, FESC; Martin Köhrmann, MD; Vincent Larrue, MD; Kennedy R. Lees, MD, FRCP; Thomas Machnig, MD, MBA; Risto O. Roine, MD, PhD; Danilo Toni, MD, PhD; Geert Vanhooren, MD for the SITS-MOST Investigators

From the Department of Neurology (N.W., N.A.), Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden; the Uppsala Clinical Research Centre (N.E.), Uppsala University, Uppsala, Sweden; Wagner-Jauregg Linz, Department of Neurology (F.A.), Linz, Austria; Boehringer Ingelheim GmbH (E.B., T.M.), Ingelheim, Germany; the Department of Neurosciences (A.D.), Hospital Germans Trias i Pujol, Universitat Autonoma de Barcelona, Spain; the Department of Neurology (T.E.), Tampere University Hospital, Tampere, Finland; the Freeman Hospital Stroke Service (G.A.F.), Newcastle General Hospital, UK; Kreisklinikum Siegen (M.G.), Siegen, Germany; the Department of Neurology (W.H.), University of Heidelberg, Heidelberg, Germany; the Department of Neurology (M.G.H.), University of Heidelberg, Mannheim, Germany; the Department of Neurology (M. Kaste), Helsinki University Central Hospital, Helsinki, Finland; the Stationsarzt Stroke Unit (M. Köhrmann), Neurologische Universitätsklinik Erlangen, Germany; the Department of Neurology (V.L.), l’Hôpital de Rangueil, Toulouse, France; the Acute Stroke Unit and Cerebrovascular Clinic, Division of Cardiovascular and Medical Sciences (K.R.L.), University of Glasgow, Glasgow, UK; the Department of Neurology (R.O.R.), Turku University Hospital, Turku, Finland; the Department of Neurology (D.T.), La Sapienza University, Hospital, Rome, Italy; and the Department of Neurology (G.V.), Sint Jan, Brugge, Belgium.

Correspondence to Nils Wahlgren, MD, PhD, SITS International Coordination Office, Karolinska Stroke Research, Department of Neurology, Karolinska University Hospital–Solna, SE-171 76 Stockholm, Sweden. E-mail nils.wahlgren{at}karolinska.se

Background and Purpose— The Safe Implementation of Thrombolysis in Stroke-MOnitoring STudy (SITS-MOST) unadjusted results demonstrated that intravenous alteplase is well tolerated and that the effects were comparable with those seen in randomized, controlled trials (RCTs) when used in routine clinical practice within 3 hours of ischemic stroke onset. We aimed to identify outcome predictors and adjust the outcomes of the SITS-MOST to the baseline characteristics of RCTs.

Methods— The study population was SITS-MOST (n=6483) and pooled RCTs (n=464) patients treated with intravenous alteplase within 3 hours of stroke onset. Multivariable, backward stepwise regression analyses (until P0.10) were performed to identify the outcome predictors for SITS-MOST. Variables appearing either in the final multivariable model or differing (P<0.10) between SITS-MOST and RCTs were included in the prediction model for the adjustment of outcomes. Main outcome measures were symptomatic intracerebral hemorrhage, defined as National Institutes of Health Stroke Scale deterioration 1 within 7 days with any hemorrhage (RCT definition), mortality, and independency as defined by modified Rankin Score of 0 to 2 at 3 months.

Results— The adjusted proportion of symptomatic intracerebral hemorrhage for SITS-MOST was 8.5% (95% CI, 7.9 to 9.0) versus 8.6% (6.3 to 11.6) for pooled RCTs; mortality was 15.5% (14.7 to 16.2) versus 17.3% (14.1 to 21.1); and independency was 50.4% (49.6 to 51.2) versus 50.1% (44.5 to 54.7), respectively. In the multivariable analysis, older age, high blood glucose, high National Institutes of Health Stroke Scale score, and current infarction on imaging scans were related to poor outcome in all parameters. Systolic blood pressure, atrial fibrillation, and weight were additional predictors of symptomatic intracerebral hemorrhage. Current smokers had a lower rate of symptomatic intracerebral hemorrhage. Disability before current stroke (modified Rankin Score 2 to 5), diastolic blood pressure, antiplatelet other than aspirin, congestive heart failure, patients treated in new centers, and male sex were related to high mortality at 3 months.

Conclusions— The adjusted outcomes from SITS-MOST were almost identical to those in relevant RCTs and reinforce the conclusion drawn previously in the unadjusted analysis. We identified several important outcome predictors to better identify patients suitable for thrombolysis.

Key Words: monitoring • multivariate • safety • stroke • thrombolysis

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