Background and purpose: Despite a significant reduction of angiographic vasospasm, the reduction of poor functional outcome in clinical trials on aneurysmal subarachnoid hemorrhage (SAH) remains challenging. While there is general consensus that vasospasm is associated with delayed cerebral ischemia (DCI), cerebral infarction, poor functional outcome, and mortality after SAH, causal relationships are subject to discussion. Therefore, it was the aim of our study to investigate the relationship between various outcome measures and poor functional outcome in clinical trials on pharmaceutical treatment of SAH.
Methods: Based on data from two systematic reviews and a post hoc exploratory analysis, the relationship between the following outcome measures was investigated: (1) radiographic vasospasm, (2) DCI, (3) cerebral infarction, (4) poor functional outcome, and (5) death.
Results: A reduction of angiographic vasospasm did not correlate with an improvement on dichotomous Glasgow Outcome Scale/modified Rankin Scale (GOS/mRS). In contrast, a reduction of cerebral infarction correlated with better neurological outcomes. The heterogeneous definition of DCI in previous clinical trials did not allow pooling of the data.
Conclusion: Future clinical trials may use cerebral infarction and functional outcome as main outcome measures to -investigate the true impact of an intervention, assuming that the intervention targets cerebral infarction and hereby improves outcome.