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Background and purpose: Polypharmacy 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. Methods: This 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. Results: 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 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). Conclusion: 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. [ABSTRACT FROM AUTHOR]

Background and purpose: Blood pressure (BP) variability has been associated with worse neurological outcomes in acute ischaemic stroke (AIS) patients receiving treatment with intravenous thrombolysis (IVT). However, no study to date has investigated whether pulse pressure (PP) variability may be a superior indicator of the total cardiovascular risk, as measured by clinical outcomes. Methods: Pulse pressure variability was calculated from 24‐h PP measurements following tissue plasminogen activator bolus in AIS patients enrolled in the Combined Lysis of Thrombus using Ultrasound and Systemic Tissue Plasminogen Activator for Emergent Revascularization (CLOTBUST‐ER) trial. The outcomes of interest were the pre‐specified efficacy and safety end‐points of CLOTBUST‐ER. All associations were adjusted for potential confounders in multivariable regression models. Results: Data from 674 participants was analyzed. PP variability was identified as the BP parameter with the most parsimonious fit in multivariable models of all outcomes, and was independently associated (P < 0.001) with lower likelihood of both 24‐h neurological improvement and 90‐day independent functional outcome. PP variability was also independently related to increased odds of any intracranial bleeding (P = 0.011) and 90‐day mortality (P < 0.001). Every 5‐mmHg increase in the 24‐h PP variability was independently associated with a 36% decrease in the likelihood of 90‐day independent functional outcome (adjusted odds ratio 0.64, 95% confidence interval 0.52–0.80) and a 60% increase in the odds of 90‐day mortality (adjusted odds ratio 1.60, 95% confidence interval 1.23–2.07). PP variability was not associated with symptomatic intracranial bleeding at either 24 or 36 h after IVT administration. Conclusions: Increased PP variability appears to be independently associated with adverse short‐term and long‐term functional outcomes of AIS patients treated with IVT. [ABSTRACT FROM AUTHOR]