Nassiri F, Ibrahim GM, Badhiwala JH, et al. Neurocrit Care. 2016;25:351-8.
Study Question: Does exposure to non-steroidal anti-inflammatory drugs (NSAIDs) improve clinical outcomes after aneurysmal subarachnoid hemorrhage (aSAH)?
Study Description: This study performed a post-hoc analysis of patients enrolled in the CONSCIOUS-1 trial, a placebo-controlled study of clazosentan. Patients had confirmed aSAH and were managed per the admitting physician, including administration of nimodipine. Patients had to have presented with a World Federation of Neurosurgical Societies (WFNS) grade of I to IV on admission or with a grade V, with subsequent improvement to a grade IV or less after intervention. Aneurysms were secured by either coiling or clipping. Patients who received NSAIDs including salicylates, ibuprofen, naproxen, indomethacin, ketorolac, diclofenac, meloxicam, or cyclooxygenase-2 inhibitors, were identified for a period of 14 days after aneurysmal rupture. Propensity score matching was performed with exposure to NSAID administration at any point during treatment. The following covariates were balanced: age, sex, baseline National Institutes of Health Stroke Scale (NIHSS) score, WFNS grade at admission, aneurysm securement method, and SAH clot burden. Clinical outcomes included 6-week mortality, 12-week modified Rankin scale (mRS) score and delayed ischemic neurological deficit (DIND).
Results: A total of 89 patients who received NSAIDs were propensity-matched to 89 control patients. The mean age was 50.6 ± 10.2 years, and most patients were female (71.9%). There were no significant differences between study groups with respect to baseline clinical, demographic, or radiographic characteristics. The 6-week mortality rate was lower in the NSAID cohort, compared to matched controls (1.1 vs. 8.8%; OR 8.61; 95% CI 1.11-389.22; p = 0.035). Likelihood of achieving a good functional outcome (mRS score <2) at 6 weeks was numerically higher in the NSAID cohort (80.9 vs. 68.5%; OR 1.93; 95% CI 0.92-4.15; p = 0.083). There were no differences in the proportions of patients who developed DIND, delayed cerebral ischemia, angiographic vasospasm, or required rescue therapy. Patients who received NSAIDs also had reduced ICU length of stay (23.6 vs. 30.8 days; p = 0.009) and a numerically shorter hospital length of stay (45.1 vs. 52.6 days; p = 0.053).
Conclusion(s): The administration of NSAIDs while in hospital after SAH resulted in reduced mortality and improved functional outcomes.
Perspective: The mechanism of the potential benefit of NSAIDs in SAH largely revolves around the decrease in inflammation that NSAIDs may cause. The conclusion of this trial is premature. There was no description of type, dose, or duration of NSAIDs therapy. There were also no mentions of control for comorbidities or cause of death. As with the early statin trials in aSAH, one study suggested significant benefits in morbidity and mortality, but this was later invalidated by a larger, well-designed analysis. Additionally, given the wide 95% confidence interval for the 6-week mortality endpoint, it appears that this study may have been underpowered. This concept will require further validation before it should be incorporated into practice.