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

Abstract

Background and purposePolypharmacy is an important challenge in clinical practice. Our aim was to determine the effect of polypharmacy on functional outcome and treatment effect of alteplase in acute ischaemic stroke.MethodsThis was a post hoc analysis of the randomized, placebo‐controlled WAKE‐UP trial of magnetic resonance imaging guided intravenous alteplase in unknown onset stroke. Polypharmacy was defined as an intake of five or more medications at baseline. Comorbidities were assessed by the Charlson Comorbidity Index (CCI). The primary efficacy variable was favourable outcome defined by a score of 0–1 on the modified Rankin Scale at 90 days. Logistic regression analysis was used to test for an association of polypharmacy with functional outcome, and for interaction of polypharmacy and the effect of thrombolysis.ResultsPolypharmacy 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 favourable outcome (adjusted odds ratio 0.50, 95% confidence interval 0.30–0.85; p = 0.0099), whilst the CCI score was not. Treatment with alteplase was associated with higher odds of favourable outcome in both groups, with no heterogeneity of treatment effect (test for interaction of treatment and polypharmacy, p = 0.29).ConclusionIn 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.

Effect of Comorbidity Burden and Polypharmacy on Poor Functional Outcome in Acute Ischemic Stroke

“…Our results confirmed a high prevalence of polypharmacy in stroke patients with up to 45% of our patients taking 5 or more medications [16,17,19]. Polypharmacy in stroke patients have been reported to be associated with poor functional outcome [15]. In accordance to that, poor functional outcome was also more common in our patients with polypharmacy.…”

“…The highest level of prescribing is observed in patients with cardiovascular risk factors [13], especially diabetes and coronary heart disease [14]. In stroke patients polypharmacy is associated with worse functional outcome [15]. Furthermore, the intake of a higher number of drugs is associated with lower possibility of discharge home [16], with the severity of poststroke fatigue [17], progression of cognitive impairment [18], and increased number of falls [19].…”

Higher comorbidity burden is associated with lower self-reported quality of life after stroke

“…Polypharmacy was present in 31.5% of our patients, which is in the upper range of reported polypharmacy rates between 10 and 30% in previous studies ( 28 , 31 – 33 ). While in univariate analysis, polypharmacy had a negative association with both outcome measures, this association was no longer present in multivariate analysis.…”

“…A high comorbidity burden in patients with AIS is a growing challenge in clinical practice and patient management. Previous studies reported 19% to 64% of stroke patients presenting with a CCI Score ≥2 ( 27 , 28 ). In an aging society, the comorbidity burden of patients is likely to increase further.…”

“…While in univariate analysis, polypharmacy had a negative association with both outcome measures, this association was no longer present in multivariate analysis. A post-hoc analysis of “WAKE UP” showed an association of polypharmacy with worse functional outcome independent of CCI ( 28 ). The authors discussed the possible attribution of their findings to a selection effect caused by the strict in- and exclusion criteria in this randomized controlled trial.…”