TY - JOUR
T1 - Refinement of the magnetic resonance diffusion-perfusion mismatch concept for thrombolytic patient selection
T2 - Insights from the desmoteplase in acute stroke trials
AU - Warach, Steven
AU - Al-Rawi, Yasir
AU - Furlan, Anthony J.
AU - Fiebach, Jochen B.
AU - Wintermark, Max
AU - Lindstén, Annika
AU - Smyej, Jamal
AU - Bharucha, David B.
AU - Pedraza, Salvador
AU - Rowley, Howard A.
PY - 2012/9
Y1 - 2012/9
N2 - BACKGROUND AND PURPOSE-: The DIAS-2 study was the only large, randomized, intravenous, thrombolytic trial that selected patients based on the presence of ischemic penumbra. However, DIAS-2 did not confirm the positive findings of the smaller DEDAS and DIAS trials, which also used penumbral selection. Therefore, a reevaluation of the penumbra selection strategy is warranted. METHODS-: In post hoc analyses we assessed the relationships of magnetic resonance imaging-measured lesion volumes with clinical measures in DIAS-2, and the relationships of the presence and size of the diffusion-perfusion mismatch with the clinical effect of desmoteplase in DIAS-2 and in pooled data from DIAS, DEDAS, and DIAS-2. RESULTS-: In DIAS-2, lesion volumes correlated with National Institutes of Health Stroke Scale (NIHSS) at both baseline and final time points (P<0.0001), and lesion growth was inversely related to good clinical outcome (P=0.004). In the pooled analysis, desmoteplase was associated with 47% clinical response rate (n=143) vs 34% in placebo (n=73; P=0.08). For both the pooled sample and for DIAS-2, increasing the minimum baseline mismatch volume (MMV) for inclusion increased the desmoteplase effect size. The odds ratio for good clinical response between desmoteplase and placebo treatment was 2.83 (95% confidence interval, 1.16-6.94; P=0.023) for MMV >60 mL. Increasing the minimum NIHSS score for inclusion did not affect treatment effect size. CONCLUSIONS-: Pooled across all desmoteplase trials, desmoteplase appears beneficial in patients with large MMV and ineffective in patients with small MMV. These results support a modified diffusion-perfusion mismatch hypothesis for patient selection in later time-window thrombolytic trials.
AB - BACKGROUND AND PURPOSE-: The DIAS-2 study was the only large, randomized, intravenous, thrombolytic trial that selected patients based on the presence of ischemic penumbra. However, DIAS-2 did not confirm the positive findings of the smaller DEDAS and DIAS trials, which also used penumbral selection. Therefore, a reevaluation of the penumbra selection strategy is warranted. METHODS-: In post hoc analyses we assessed the relationships of magnetic resonance imaging-measured lesion volumes with clinical measures in DIAS-2, and the relationships of the presence and size of the diffusion-perfusion mismatch with the clinical effect of desmoteplase in DIAS-2 and in pooled data from DIAS, DEDAS, and DIAS-2. RESULTS-: In DIAS-2, lesion volumes correlated with National Institutes of Health Stroke Scale (NIHSS) at both baseline and final time points (P<0.0001), and lesion growth was inversely related to good clinical outcome (P=0.004). In the pooled analysis, desmoteplase was associated with 47% clinical response rate (n=143) vs 34% in placebo (n=73; P=0.08). For both the pooled sample and for DIAS-2, increasing the minimum baseline mismatch volume (MMV) for inclusion increased the desmoteplase effect size. The odds ratio for good clinical response between desmoteplase and placebo treatment was 2.83 (95% confidence interval, 1.16-6.94; P=0.023) for MMV >60 mL. Increasing the minimum NIHSS score for inclusion did not affect treatment effect size. CONCLUSIONS-: Pooled across all desmoteplase trials, desmoteplase appears beneficial in patients with large MMV and ineffective in patients with small MMV. These results support a modified diffusion-perfusion mismatch hypothesis for patient selection in later time-window thrombolytic trials.
KW - acute cerebral infarction
KW - desmoteplase
KW - diffusion-weighted imaging
KW - magnetic resonance imaging
KW - mismatch
KW - perfusion
KW - stroke
KW - thrombolysis
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UR - http://www.scopus.com/inward/citedby.url?scp=84865607691&partnerID=8YFLogxK
U2 - 10.1161/STROKEAHA.111.642348
DO - 10.1161/STROKEAHA.111.642348
M3 - Article
C2 - 22738918
AN - SCOPUS:84865607691
SN - 0039-2499
VL - 43
SP - 2313
EP - 2318
JO - Stroke
JF - Stroke
IS - 9
ER -