Key result
Hypertension in acute ischemic stroke models is linked to lower therapy efficacy, especially in larger infarcts.
Why the study?
Procedures for management of hypertension in acute stroke and its impact on candidate stroke therapies are less certain.
Does hypertension impact the efficacy of candidate stroke therapies on infarct size in animal models of acute ischemic stroke?
Meta-Analysis (n=47,899)
Does hypertension impact the efficacy of candidate stroke therapies on infarct size in animal models of acute ischemic stroke?
Hypertension significantly alters the efficacy of experimental stroke therapies in animal models, suggesting that standard preclinical testing in normotensive animals may overestimate clinical efficacy.
Requires hypertensive models for stroke therapy testing; challenges translation from normotensive preclinical data.
UNLABELLED: Hypertension is an established target for long-term stroke prevention but procedures for management of hypertension in acute stroke are less certain. Here, we analyze basic science data to examine the impact of hypertension on candidate stroke therapies and of anti-hypertensive treatments on stroke outcome. METHODS: Data were pooled from 3,288 acute ischemic stroke experiments (47,899 animals) testing the effect of therapies on infarct size (published 1978-2010). Data were combined using meta-analysis and meta-regression, partitioned on the basis of hypertension, stroke model, and therapy. RESULTS: Hypertensive animals were used in 10% of experiments testing 502 therapies. Hypertension was associated with lower treatment efficacy, especially in larger infarcts. Overall, anti-hypertensives did not provide greater benefit than other drugs, although benefits were evident in hypertensive animals even when given after stroke onset. Fifty-eight therapies were tested in both normotensive and hypertensive animals: some demonstrated superior efficacy in hypertensive animals (hypothermia) while others worked better in normotensive animals (tissue plasminogen activator, anesthetic agents). DISCUSSION: Hypertension has a significant effect on the efficacy of candidate stroke drugs: standard basic science testing may overestimate the efficacy which could be reasonably expected from certain therapies and for hypertensive patients with large or temporary occlusions.
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O’Collins et al. (2013) conducted a meta-analysis in acute ischemic stroke (n=47,899). Hypertension vs. Normotension was evaluated on infarct size. Hypertension in animal models of acute ischemic stroke was associated with lower treatment efficacy of candidate stroke therapies, especially in larger infarcts.
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