Polypharmacy, functional outcome, and treatment effect of intravenous alteplase for acute ischemic stroke.

Abstract

Polypharmacy is an important challenge in clinical practice. We aimed at determining the effect of polypharmacy on functional outcome and treatment effect of alteplase in acute ischemic stroke. Post-hoc analysis of the randomized, placebo-controlled WAKE-UP trial of MRI-guided intravenous alteplase in unknown onset stroke. Polypharmacy was defined as intake of ≥5 medications at baseline. Comorbidities were assessed by the Charlson Comorbidity Index (CCI). The primary efficacy variable was favorable outcome defined by a score of 0-1 on the modified Rankin Scale at 90 days. We used logistic regression analysis to test for an association of polypharmacy with functional outcome, and for interaction of polypharmacy and the effect of thrombolysis. Polypharmacy was present in 133/503 (26%) patients. Patients with polypharmacy were older (mean age 70 vs 64 years; P<0.0001) and had a higher score on the National Institutes of Health Stroke Scale at baseline (median 7 vs 5; P=0.0007). A comorbidity load defined by a CCI score ≥2 was more frequent in patients with polypharmacy (48% vs 8%; P<0.001). Polypharmacy was associated with lower odds of favorable outcome (adjusted odds ratio 0.50, 95% CI, 0.30-0.85; P=0.0099), while the CCI score was not. Treatment with alteplase was associated with higher odds of favorable outcome in both groups, with no heterogeneity of treatment effect (test for interaction of treatment and polypharmacy, P=0.29). In stroke patients, polypharmacy is associated with worse functional outcome after intravenous thrombolysis independent of comorbidities. However, polypharmacy does not interact with the beneficial effect of alteplase.