A pooled analysis of seven trials suggests follow-up infarct volume might be a strong prognostic biomarker irrespective of imaging modality and time to follow-up imaging.
New data provide confirmatory evidence that follow-up infarct volume (FIV) is a strong and early predictor of treatment efficacy in patients with acute ischemic stroke, suggesting that with further study it might be suitable as a prognostic biomarker.
“We found a strong association between FIV and 90-day mRS score, regardless of imaging approach, which is a crucial first step for a potential surrogate endpoint,” write Anna M. M. Boers, MSc (Academic Medical Centre, Amsterdam, the Netherlands), and colleagues in a paper published recently in the Journal of NeuroInterventional Surgery.
For the study, known as the HERMES collaboration, the researchers examined patient-level data from seven major randomized controlled trials of endovascular therapy in acute ischemic stroke (ESCAPE, EXTEND-IA, SWIFT PRIME, REVASCAT, MR CLEAN, PISTE, and THRACE). Patients in all of these trials had FIV assessed at 12 hours to 2 weeks with either CT or MRI.
The primary outcome for HERMES was the degree of disability as scored on the modified Rankin Scale at 90 days.
Among the 1,665 patients, median baseline NIHSS score was 17 (interquartile range [IQR] 13-21), 44.4% had a left-sided infarct, 50.7% were randomized to endovascular therapy, 90% received intravenous thrombolysis, and 83% underwent noncontrast CT follow-up imaging. The median FIV was 41 mL (IQR 14-120 mL), and median mRS at 90 days was 3 (IQR 2-4). Nearly 40% of patients had an mRS score of 0-2 by 90 days, indicating functional independence.
FIV was observed to be progressively larger as mRS score increased. The strength of correlation between FIV and mRS score was moderate and statistically significant (P < 0.0001).
Boers and colleagues conclude that an unfavorable outcome (mRS 3-6) is almost inevitable when the follow-up infarct volume exceeds 133 mL, with a specificity of 95%. On both CT and MRI, follow-up volume was strongly associated with mRS score, but differences were seen, with larger volumes observed when the imaging modality was CT. The researchers say this may be due to the fact that trials with stricter inclusion criteria towards smaller cores at baseline routinely performed more MRI.
Role for FIV in Assessing Poor Outcomes
“What is important,” they write, “is that we demonstrated similar correlations with functional outcome for both CT and MRI.” Equally important, they add, is that CT is considerably less expensive and more widely available than MRI in many countries.
Boers and colleagues say their estimates of FIV thresholds “may help to identify patients for whom reaching functional independence at 90 days is unlikely, potentially influencing patient management after stroke, particularly decisions taken on disposition.”
Importantly, the findings also suggest that FIV can be measured as early as 12 hours after treatment, which is advantageous because most patients are still at the intervention hospital at that point.
“Future studies must examine the full potential of FIV as a surrogate through formal testing of the causal chain of treatment–FIV–functional outcome,” Boers and colleagues conclude.
Sources:
Boers AMM, Jansen IGH, Beenen LFM, et al. Association of follow-up infarct volume with functional outcome in acute ischemic stroke: a pooled analysis of seven randomized trials. J NeuroIntervent Surg. 2018;Epub ahead of print.
Disclosures:
- The study was supported by Medtronic through an unrestricted grant to the University of Calgary.
- Boers reports owing stock in Nico.lab, a company that focuses on medical imaging software.
