Assessing combination treatments in acute stroke: preclinical experiences.
BACKGROUND
Acute ischemic stroke is a complex disease. Treatment success may require combining different therapeutic approaches. An obvious treatment combination in acute ischemic stroke is a thrombolytic therapy, adjuvant with a neuroprotective agent to have better stroke recovery.


RESULTS
Complete factorial designs can assess the synergy of combination treatments and distinguish them from supper-additive, additive or sub-additive effects. A factorial design, a two-way analysis of variance and a novel graphic technique can detect and illustrate interactions of two treatments, which were used to evaluate combination treatments to extend the therapeutic window for thrombolytic therapy in an embolic stroke model on rats. We hypothesized synergy or additive effects on stroke recovery when combining thrombolytic therapy with either an antagonist to the integrin CD11b/CD18 (UK-279,276) or a glycoprotein IIb/IIIa receptor inhibitor.


CONCLUSIONS
Factorial designs offer an efficient approach to study synergistic effects of two treatments. Our graphical technique provides a powerful, intuitive and quantitative explanation of joint treatment effects. Combining thrombolytic therapy with a neuroprotectant yielded a super-additive or additive treatment effect for two preclinical experiments designed to extend the thrombolytic therapeutic window for stroke.
Lu
Mei
M
Department of Biostatistics and Research Epidemiology, Henry Ford Health Sciences Center, One Ford Place 3E, Detroit, MI 48202, USA. mlu1@hfhs.org
Krams
Michael
M
Zhang
Li
L
Zhang
Zheng Gang
ZG
Chopp
Michael
M
D000704:Analysis of Variance; D004353:Drug Evaluation, Preclinical; D004359:Drug Therapy, Combination; D005163:Factor Analysis, Statistical; D006801:Humans; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D020521:Stroke / Q000628:therapy*; D015912:Thrombolytic Therapy / Q000379:methods*; D016896:Treatment Outcome
D018696:Neuroprotective Agents