Can multivariable risk-benefit profiling be used to select treatment-favorable patients for thrombolysis in stroke in the 3- to 6-hour time window?
OBJECTIVE
The Stroke-Thrombolytic Predictive Instrument (Stroke-TPI) uses multivariate equations to predict outcomes with and without thrombolysis. We sought to examine whether such a multivariate predictive instrument might be useful in selecting patients with a favorable risk-benefit treatment profile for therapy after 3 hours.


METHODS
We explored outcomes in patients from 5 major randomized clinical trials testing intravenous recombinant tissue plasminogen activator (rt-PA) classified by the Stroke-TPI as "treatment-favorable" or "treatment-unfavorable." We used iterative bootstrap re-sampling to estimate how such a model would perform on independent test data.


RESULTS
Among patients treated within the 3- to 6-hour window, 67% of patients were classified by Stroke-TPI predicted outcomes as "treatment-favorable" and 33% were classified as "treatment-unfavorable." Outcomes in the treatment-favorable group demonstrated benefit for thrombolysis (modified Rankin Scale score < or =1: 44.0% with rt-PA versus 34.2 with placebo, P=0.005), whereas harm was demonstrated in the treatment-unfavorable group (modified Rankin Scale score < or =1: 31.3% with rt-PA versus 38.3% with placebo; P=0.004). Bootstrap resampling with complete cross-validation showed that the absolute margin of benefit in the treatment-favorable group diminished on average by 36% between derivation and independent validation sets, but still represented a significant tripling of improvement in benefit compared with conventional inclusion criteria (5.2% [interquartile range, 1.7% to 8.6%] versus 1.8% [interquartile range, -0.5 to 4.1], P<0.0001).


CONCLUSIONS
Such multivariable risk-benefit profiling may be useful in the selection of acute stroke patients for rt-PA therapy even more than 3 hours after symptom onset. Prospective testing is indicated.
Kent
David M
DM
Institute for Clinical Research and Health Policy Studies, Tufts-New England Medical Center, Tufts University School of Medicine, Boston, MA 02111, USA. Dkent1@tufts-nemc.org
Selker
Harry P
HP
Ruthazer
Robin
R
Bluhmki
Erich
E
Hacke
Werner
W
D000368:Aged; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D018579:Patient Selection; D011237:Predictive Value of Tests; D018570:Risk Assessment; D020521:Stroke / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology*; D015912:Thrombolytic Therapy / Q000379:methods; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use; D016896:Treatment Outcome
D010959:Tissue Plasminogen Activator