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Original Investigation |

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

Ying Xian, MD, PhD1; Jerome J. Federspiel, MD, PhD2,3; Maria Grau-Sepulveda, MD, MPH1; Adrian F. Hernandez, MD, MHS1; Lee H. Schwamm, MD4; Deepak L. Bhatt, MD, MPH5; Eric E. Smith, MD, MPH6,7; Mathew J. Reeves, PhD8; Laine Thomas, PhD1; Laura Webb, MS1; Janet Prvu Bettger, ScD1; Daniel T. Laskowitz, MD, MHS9; Gregg C. Fonarow, MD10; Eric D. Peterson, MD, MPH1
[+] Author Affiliations
1Duke Clinical Research Institute, Durham, North Carolina
2medical student at University of North Carolina School of Medicine, Chapel Hill
3currently with Department of Gynecology and Obstetrics, Johns Hopkins School of Medicine, Baltimore, Maryland
4Division of Neurology, Massachusetts General Hospital, Boston
5Brigham and Women’s Hospital Heart and Vascular Center and Harvard Medical School, Boston, Massachusetts
6Department of Clinical Neurosciences, University of Calgary, Calgary, Alberta, Canada
7Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada
8Department of Epidemiology, Michigan State University, East Lansing
9Department of Neurology, Duke University Medical Center, Durham, North Carolina
10Division of Cardiology, University of California, Los Angeles
JAMA Neurol. 2016;73(1):50-59. doi:10.1001/jamaneurol.2015.3106.
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Importance  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.

Objective  To assess the risks and benefits associated with prestroke antiplatelet therapy among patients with ischemic stroke who receive intravenous tPA.

Design, Setting, and Participants  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.

Exposures  Prestroke antiplatelet therapy before tPA administration for acute ischemic stroke.

Main Outcomes and Measures  Symptomatic intracranial hemorrhage (sICH), in-hospital mortality, discharge ambulatory status, and modified Rankin Scale score (range, 0 [no symptoms] to 6 [death]).

Results  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).

Conclusions and Relevance  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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Figure 1.
Study Population

INR indicates international normalized ratio; GWTG-Stroke, American Heart Association and American Stroke Association Get With the Guidelines–Stroke program; and tPA, tissue plasminogen activator.

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Figure 2.
Preadmission Antiplatelet Therapy and Symptomatic Intracranial Hemorrhage (sICH)

Data are given overall and in clinically relevant subgroups. AOR indicates adjusted odds ratio; CAD, coronary artery disease; MI, myocardial infarction; and TIA, transient ischemic attack.

aIncludes patients admitted October 1, 2012, or later.

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