History of Nonsteroidal Anti-inflammatory Drug Use and Functional Outcomes After Spontaneous Intracerebral Hemorrhage

Preclinical and clinical studies have suggested a potential benefit from COX-2 inhibition on secondary injury activation after spontaneous intracerebral hemorrhage (ICH). The aim of this study was to investigate the effect of pre-admission NSAID use on functional recovery in spontaneous ICH patients.

Consecutive adult ICH patients enrolled in the Intracerebral Hemorrhage Outcomes Project (2009-2018) with available 90-day follow-up data were included. Patients were categorized as NSAID (daily COX inhibitor use ≤ 7 days prior to ICH) and non-NSAID users (no daily COX inhibitor use ≤ 7 days prior to ICH). Primary outcome was the ordinal 90-day modified Rankin Scale (mRS) score. Outcomes were compared between cohorts using multivariable regression and propensity score-matched analyses. A secondary analysis excluding aspirin users was performed.

The NSAID and non-NSAID cohorts comprised 228 and 361 patients, respectively. After 1:1 matching, the matched cohorts each comprised 140 patients. The 90-day mRS were comparable between the NSAID and non-NSAID cohorts in both the unmatched (aOR = 0.914 [0.626-1.336], p = 0.644) and matched (aOR = 0.650 [0.392-1.080], p = 0.097) analyses. The likelihood of recurrent ICH at 90 days was also comparable between the NSAID and non-NSAID cohorts in both the unmatched (aOR = 0.845 [0.359-1.992], p = 0.701) and matched analyses (aOR = 0.732 [0.241-2.220], p = 0.581). In the secondary analysis, the non-aspirin NSAID and non-NSAID cohorts comprised 38 and 361 patients, respectively. After 1:1 matching, the matched cohorts each comprised 38 patients. The 90-day mRS were comparable between the non-aspirin NSAID and non-NSAID cohorts in both the unmatched (aOR = 0.615 [0.343-1.101], p = 0.102) and matched (aOR = 0.525 [0.219-1.254], p = 0.147) analyses. The likelihood of recurrent ICH at 90 days was also comparable between the non-aspirin NSAID and non-NSAID cohorts in both the unmatched (aOR = 2.644 [0.258-27.091], p = 0.413) and matched (aOR = 2.586 [0.228-29.309], p = 0.443) analyses. After the exclusion of patients with DNR or withdrawal of care status, NSAID use was associated with lower mRS at 90 days (aOR = 0.379 [0.212-0.679], p = 0.001), lower mRS at hospital discharge (aOR = 0.505 [0.278-0.919], p = 0.025) and lower 90-day mortality rates (aOR = 0.309 [0.108-0.877], p = 0.027).

History of nonselective COX inhibition may affect functional outcomes in ICH patients. Pre-admission NSAID use did not appear to worsen the severity of presenting ICH or increase the risk of recurrent ICH. Additional clinical studies may be warranted to investigate the effects of pre-admission NSAID use on ICH outcomes.