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

Abstract

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 anti...

Intravenous Thrombolysis for Acute Ischemic Stroke in Patients Receiving Antiplatelet Therapy: A Systematic Review and Meta‐analysis of 19 Studies

“…However, when adjusted for confounders, the independent association between pre‐existing antiplatelet therapy and unfavorable outcomes became insignificant (adjusted OR 1.09, 95% CI 0.96–1.24). Although a high level of heterogeneity was observed in the adjusted estimates ( I 2 =76.2%, P =0.006), we were able to locate the major sources of heterogeneity through subgroup analysis (Table 4), which included the 1 study that provided only data on outcome at hospital discharge 29. The pooled adjusted estimates remained similar after the exclusion of this study (OR 1.07, 95% CI 0.83–1.37).…”

“…All studies with follow‐up patients for functional outcomes defined favorable outcome as mRS scores of either 0 to 2 or 0 to 1 on poststroke day 90, except for 1 study that recorded patient functional outcomes at hospital discharge 29. Our pooled analysis of crude ORs showed that patients taking prior antiplatelet medications tended to have lower odds of reaching favorable functional outcomes (OR 0.86, 95% CI 0.80–0.93) (Figure 2B).…”

“…The outcomes of study quality assessment are as follows: 8 studies scored 9 (Xian et al,29 Pan et al,25 Meurer et al,24 Ibrahim et al,20 Dorado et al,19 Diedler et al,18 Cucchiara et al,16 and Uyttenboogaart et al13), 3 studies scored 8 (Bluhmki et al,15 Bravo et al,12 and Tanne et al9), and 7 studies scored 7 (Meseguer et al,27 Watson‐Fargie et al,28 Lindley et al,26 Martí‐Fàbregas et al,11 Schmülling et al,10 Šaňák et al,21 and Hermann et al17). Those scores served as differentiators in a subgroup analysis that divided studies into 2 groups (NOS >7 and NOS ≤7).…”

“…Of the 7 studies that provided information on mortality, one assessed in‐hospital mortality,29 one reported both 7‐ and 90‐day data,26 and the others reported mortality on poststroke day 90. Although pooled unadjusted results indicated increased odds of all‐cause mortality among patients receiving prestroke antiplatelet medications (OR 1.46, 95% CI 1.22–1.75) (Figure 2C), pooled adjusted ORs did not reveal any significant correlations (OR 1.02, 95% CI 0.98–1.07) (Figure 3C).…”

“…Meta‐analyses based on only a limited number of those studies were therefore subject to inaccuracies and biases, because they did not allow us to synthesize adjusted results or to perform comprehensive subgroup analyses 5, 6. Now with data from some of the largest registries having surfaced, our attention is once again brought to the subject of intravenous thrombolysis in patients receiving antiplatelet medications 25, 26, 29. Xian et al concluded recently that those patients had better functional outcomes despite higher risks for symptomatic intracranial hemorrhage (sICH),29 yet it needs to be pointed out that they adopted certain study designs and outcome definitions that were not completely compatible with those of many previous studies.…”