Introduction: Although intra-arterial/endovascular (IA) stroke therapies are widely employed, there has been a paucity of randomized clinical trials (RCT) to support their use. In lieu of RCTs, case series are often compared to each other or to other RCTs. However, stroke outcome is highly dependent on baseline factors such as severity and age. Because those factors have a complex relationship, comparisons are often unreliable. Even with the inclusion of a control arm, imbalances often complicate valid conclusions. In order to provide meaningful comparisons, we developed pPREDICTS, that generates a surrogate control outcome function based on the baseline factors and outcomes of the placebo arms of published RCTs (Mandava & Kent Stroke 2009). pPREDICTS now includes 24 RCTs representing 7400 subjects and explains more than 80% of the variance of mortality and functional outcome (mRS). In this study, we applied pPREDICTS to published IA series and calculated benefit/risk for each based on differences from predicted outcome at comparable baseline NIHSS and age. We performed the same analysis with intravenous (IV) thrombolytic RCTs in order to gauge relative efficacy.
Methods: We identified 51 IA and 22 IV studies that included baseline NIHSS, age, time window, and outcomes (mRS 0-2 and mortality) and with N > 10. Proportions of subjects that died or achieved mRS 0-2 were subdivided by time window. Publication bias, the apparent greater benefit in those trials with smaller N, was corrected by trim and fill using the pPREDICTS outcome as the surrogate baseline (Mandava & Kent Neurology 2007). Data is represented as mean + 95% confidence interval.
Results: The IA series had a higher baseline NIHSS than the IV trials (17.7+3.2 vs 12.5+3.2; p<.001), so likely represented a different set of patients. We found frequent instances of publication bias, particularly in the IA trials at 6 hrs. When compared to the predicted outcome for each trial at its comparable baseline factors, odds ratios for both IV and IA showed decreasing, but significant improvement in mRS without excess mortality ( Figure ) up to 6 hour time period. However, beyond 6 hours there was excess mortality seen with IA therapy.
Conclusion: Unlike other systematic or meta-analysis, by comparing individual treatment arms to a continuous placebo outcome model at baseline factors similar to their own we avoided the need to adjust for imbalances. Decreasing, but potential benefit of both IA and IV therapies was found up to 6 hours, but with higher mortality for IA at > 6 hrs. Analysis will be presented of which clinical factors predicted the best outcomes.