Risks and Benefits Associated With Prestroke Antiplatelet Therapy Among Patients With Acute Ischemic Stroke Treated With Intravenous Tissue Plasminogen Activator.

Abstract

Intravenous tissue plasminogen activator (tPA) is known to improve outcomes in ischemic stroke; however, many patients may have been receiving antiplatelet therapy before acute ischemic stroke and could face an increased risk for bleeding when treated with tPA.To assess the risks and benefits associated with prestroke antiplatelet therapy among patients with ischemic stroke who receive intravenous tPA.This observational study used data from the American Heart Association and American Stroke Association Get With the Guidelines-Stroke registry, which included 85 072 adult patients with ischemic stroke who received intravenous tPA in 1545 registry hospitals from January 1, 2009, through March 31, 2015. Data were analyzed during the same period.Prestroke antiplatelet therapy before tPA administration for acute ischemic stroke.Symptomatic intracranial hemorrhage (sICH), in-hospital mortality, discharge ambulatory status, and modified Rankin Scale score (range, 0 [no symptoms] to 6 [death]).Of the 85 072 registry patients, 38 844 (45.7%) were receiving antiplatelet therapy before admission; 46 228 patients (54.3%) were not. Patients receiving antiplatelet therapy were older (median [25th-75th percentile] age, 76 [65-84] vs 68 [56-80] years) and had a higher prevalence of cardiovascular risk factors. The unadjusted rate of sICH was higher in patients receiving antiplatelet therapy (5.0% vs 3.7%). After risk adjustment, prior use of antiplatelet agents remained associated with higher odds of sICH compared with no use (adjusted odds ratio [AOR], 1.18 [95% CI, 1.10-1.28]; absolute difference, +0.68% [95% CI, 0.36%-1.01%]; number needed to harm [NNH], 147). Among patients enrolled on October 1, 2012, or later, the highest odds (95% CIs) of sICH were found in 15 116 patients receiving aspirin alone (AOR, 1.19 [1.06- 1.34]; absolute difference [95% CI], +0.68% [0.21%-1.20%]; NNH, 147) and 2397 patients receiving dual antiplatelet treatment of aspirin and clopidogrel (AOR, 1.47 [1.16-1.86]; absolute difference, +1.67% [0.58%-3.00%]; NNH, 60). The risk for in-hospital mortality was similar between those who were and were not receiving antiplatelet therapy after adjustment (8.0% vs 6.6%; AOR, 1.00 [0.94-1.06]; nonsignificant absolute difference, -0.01% [-0.37% to 0.36%]). However, patients receiving antiplatelet therapy had a greater risk-adjusted likelihood of independent ambulation (42.1% vs 46.6%; AOR, 1.13 [1.08-1.17]; absolute difference, +2.23% [1.55%-2.92%]; number needed to treat, 43) and better functional outcomes (modified Rankin Scale score, 0-1) at discharge (24.1% vs 27.8%; AOR, 1.14; 1.07-1.22; absolute difference, +1.99% [0.78%-3.22%]; number needed to treat, 50).Among patients with an acute ischemic stroke treated with intravenous tPA, those receiving antiplatelet therapy before the stroke had a higher risk for sICH but better functional outcomes than those who were not receiving antiplatelet therapy.

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Citation

Published Version (Please cite this version)

10.1001/jamaneurol.2015.3106

Publication Info

Xian, Ying, Jerome J Federspiel, Maria Grau-Sepulveda, Adrian F Hernandez, Lee H Schwamm, Deepak L Bhatt, Eric E Smith, Mathew J Reeves, et al. (2016). Risks and Benefits Associated With Prestroke Antiplatelet Therapy Among Patients With Acute Ischemic Stroke Treated With Intravenous Tissue Plasminogen Activator. JAMA neurology, 73(1). pp. 50–59. 10.1001/jamaneurol.2015.3106 Retrieved from https://hdl.handle.net/10161/21716.

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Scholars@Duke

Federspiel

Jerome Jeffrey Federspiel

Assistant Professor of Obstetrics and Gynecology

Dr. Federspiel is a maternal fetal medicine physician at Duke University. His clinical and research interests focus on the care of people with cardiovascular and hematologic complications of pregnancy.

Thomas

Laine Elliott Thomas

Professor of Biostatistics & Bioinformatics

Laine Thomas, PhD, joined the Department of Biostatistics and Bioinformatics and DCRI in 2009.  She serves as Associate Chair for Equity, Diversity and Inclusion within the Department of Biostatistics and Bioinformatics and Deputy Director of Data Science and Biostatistics at the Duke Clinical Research Institute.  She is a leader in study design and development of methods for observational and pragmatic studies, with over 240 peer reviewed clinical and methodological publications arising from scientific collaboration in the therapeutic areas of cardiovascular disease, diabetes, uterine fibroids and SARS-CoV-2 virus. She led the statistical teams on the HERO COVID-19, ORBIT-AF I & II, ACTION-CMS, CHAMP-HF, and COMPARE-UF clinical registries and secondary analyses of the NAVIGATOR and ARISTOTLE clinical trials. She has served as a primary investigator and co-investigator on numerous methodological studies with funding from NIH, AHRQ, PCORI and Burroughs Wellcome Fund, addressing observational treatment comparisons, time-varying treatments, heterogeneity of treatment effects, and randomized trials augmented by synthetic controls from real world data.      

Bettger

Janet Prvu Bettger

Adjunct Associate in the Department of Orthopaedic Surgery

Dr. Bettger’s research is dedicated to establishing real world evidence aimed to improve health care quality and policies that reduce the burden of disease and disability. As a health services researcher and implementation scientist, her research extends from observational studies to randomized and pragmatic trials. She was the Founding Director of Duke Roybal Center for Translational Research in the Behavioral and Social Sciences of Aging and the Founding Director of Undergraduate Initiatives for the Duke-Margolis Center for Health Policy. She has examined implementation of several integrated care models to improve the transition home from the hospital (VERITAS with virtual exercise therapy after knee replacement, COMPASS for stroke, RECOVER for stroke in rural China, and coordinated care for trauma patients in Tanzania). She also studies implementation of community-based models of care that can prevent functional decline. These include the CTSA-funded IMPAC RCT of integrating physical therapists into primary care as first line providers to address musculoskeletal pain, the VA-funded Gerofit program of structured and progressive in-person and virtual group exercise for older Veterans, MRC-funded SINEMA RCT of a village-based model supporting stroke recovery in China, and a NIDCD study comparing three primary care protocols for older adult hearing healthcare.

In addition to the evidence translation studies in China (RECOVER and SINEMA) and Tanzania, she has partnered with experts in Singapore on stroke systems research, and worked on large cluster randomized trials to improve evidence-based care in Brazil, Peru, Argentina (BRIDGE-Stroke) and China (CNSR and Golden Bridge). To address health locally, she was the faculty sponsor to launch Exercise is Medicine at Duke and Help Desk, a student volunteer community resource navigator model addressing social determinants of health.

Dr. Bettger received her BA from the University of Western Ontario, Canada and her MS from the University of Wisconsin–LaCrosse where she studied community reintegration for stroke and brain-injured patients transitioning from hospital to home. Her doctoral training in Rehabilitation Sciences, completed at Boston University, concluded with an investigation of patterns of functional recovery and factors affecting outcomes in patients transitioning home following acute rehabilitation. While working on her doctorate, she also worked in state government as the director of the Paul Coverdell National Acute Stroke Registry. Dr. Bettger completed post-doctoral training at the University of Pennsylvania with a NIH NRSA research fellowship in neurorehabilitation, a research fellowship at the NewCourtland Center for Transitions and Health, and a Switzer Fellowship funded by the National Institute on Disability and Rehabilitation Research to study the role of the environment on functional outcomes. She completed additional research training at Duke as a mentored scholar in comparative effectiveness research funded by AHRQ. As of July 2022, she is an Adjunct Associate Professor for Duke's Department of Orthopaedics and has transitioned out of her role as Co-Director of the Duke Clinical and Translational Institute (CTSA) Pilots Accelerator Core working with NCCU. She is affiliate faculty with Duke's Science and Society, Duke-Margolis Center for Health Policy, the Duke Clinical Research Institute (DCRI) and Duke Global Health Institute (DGHI), is a Senior Fellow of the Duke Center for the Study of Aging and Human Development, and is a Fellow of the American Heart Association. 

Laskowitz

Daniel Todd Laskowitz

Professor of Neurology

Our laboratory uses molecular biology, cell culture, and animal modeling techniques to examine the CNS response to acute injury. In particular, our laboratory examines the role of microglial activation and the endogenous CNS inflammatory response in exacerbating secondary injury following acute brain insult. Much of the in vitro work in this laboratory is dedicated to elucidating cellular responses to injury with the ultimate goal of exploring new therapeutic interventions in the clinical setting of stroke, intracranial hemorrhage, and closed head injury.

In conjunction with the Multidisciplinary Neuroprotection Laboratories, we also focus on clinically relevant small animal models of acute CNS injury. For example, we have recently characterized murine models of closed head injury, subarachnoid hemorrhage, intracranial hemorrhage and perinatal hypoxia-ischemia, in addition to the standard rodent models of focal stroke and transient forebrain ischemia. Recently we have adapted several of these models from the rat to the mouse to take advantage of murine transgenic technology. The objective of these studies are two-fold: to gain better insight into the cellular responses and pathophysiology of acute brain injury, and to test novel therapeutic strategies for clinical translation. In both cell culture systems and animal models, our primary focus is on examining the role of oxidative stress and inflammatory mechanism in mediating brain injury following acute brain insult, and examining the neuroprotective effects of endogenous apolipoprotein E in the injured mammalian central nervous system.

Our laboratory is committed to translational research, and has several active clinical research protocols, which are designed to bring the research performed in the Multidisciplinary Research Laboratories to the clinical arena. These protocols are centered around patients following stroke and acute brain injury, and are primarily based out of the Emergency Room and Neurocritical Care Unit. For example, we are currently examining the role of inflammatory mediators for use as a point-of-care diagnostic marker following stroke, intracranial hemorrhage, and closed head injury. We have recently translated a novel apoE mimetic from the preclinical setting to a multi center Phase 2 trial evaluating efficacy in intracranial hemorrhage. We are also examining the functional role of different polymorphisms of of inflammatory cytokines in the setting of acute brain injury and neurological dysfunction following cardiopulmonary bypass.


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