Hyperglycemia Worsens Outcome After rt-PA Primarily in the Large-Vessel Occlusive Stroke Subtype
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ORIGINAL ARTICLE
Hyperglycemia Worsens Outcome After rt-PA Primarily in the Large-Vessel Occlusive Stroke Subtype Pitchaiah Mandava & Sharyl R. Martini & Melody Munoz & William Dalmeida & Anand K. Sarma & Jane A. Anderson & Roderic H. Fabian & Thomas A. Kent
Received: 27 October 2013 / Revised: 28 February 2014 / Accepted: 4 March 2014 # Springer Science+Business Media New York (Outside the USA) 2014
Abstract Hyperglycemia at the time of ischemic stroke has been associated with poorer outcomes. Preclinical literature suggests that hyperglycemia is an independent prognostic factor and the vasculature is more vulnerable to reperfusion injury. We applied a method to match subjects on important baseline factors to test whether, independent of stroke severity, stroke subtype influences the effect of hyperglycemia on outcome after recombinant tissue plasminogen activator (rt-PA). We reanalyzed the NINDS rt-PA dataset with respect to matching variables baseline NIHSS, age, and investigator-determined stroke subtypes small-vessel occlusive stroke (SVS), large-vessel occlusive stroke (LVS), and cardioembolic stroke (CES), above and below a glucose threshold of 150 mg/dl. Ninety-day outcomes were compared. Post hoc baseline matching was excellent in most cases. Hyperglycemia was
A preliminary version of this manuscript was presented at the International Stroke Conference, February 2011. Electronic supplementary material The online version of this article (doi:10.1007/s12975-014-0338-x) contains supplementary material, which is available to authorized users. P. Mandava (*) : T. A. Kent (*) Michael E. DeBakey Veterans Affairs Medical Center, Neurology 2B223/127, 2002 Holcombe Blvd., Houston, TX 77030, USA e-mail: [email protected] e-mail: [email protected] S. R. Martini : M. Munoz : W. Dalmeida : A. K. Sarma : J. A. Anderson : R. H. Fabian : T. A. Kent The Michael E. DeBakey Veterans Affairs Medical Center Stroke Program, Houston, TX, USA S. R. Martini : T. A. Kent Center for Translational Research in Inflammatory Diseases, Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX, USA S. R. Martini : M. Munoz : W. Dalmeida : A. K. Sarma : J. A. Anderson : R. H. Fabian : T. A. Kent Department of Neurology, Baylor College of Medicine, Houston, TX, USA
associated with worsened functional outcome mostly in the LVS subtype with increased mortality in the placebo arm (15.3 % mortality normoglycemia vs. 30.6 % hyperglycemia; p=.046), worse functional outcome in the rt-PA arm (modified Rankin Score (mRS) 0–1; 46.3 vs. 22.0 %; p=.034), and no improvement in functional outcome with rt-PA compared to placebo (mRS 0–1; 25 % in both groups). Among hyperglycemic subjects, CES subjects showed significant improvement following rtPA (p=.027). After matching for baseline severity, the influence of hyperglycemia on outcome was primarily in the LVS subtype, especially after rt-PA. This finding is consistent with a deleterious effect of hyperglycemia on ischemia/reperfusion of symptomatic large arteries. If confirmed, the particular vulnera
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