Does Current Oral Antiplatelet Agent or Subtherapeutic Anticoagulation Use Have an Effect on Tissue-Plasminogen-Activator-Mediated Recanalization Rate in Patients with Acute Ischemic Stroke?

Abstract

Objective: Our goal is to assess if current antiplatelet (AP) use has an effect on recanalization rate and outcome in acute stroke patients. Methods: We conducted a retrospective analysis of acute stroke patients who received intravenous (IV) recombinant tissue plasminogen activator (rt-PA) and had transcranial Doppler examination within 3 h of symptom onset. The TCD findings were interpreted using the Thrombolysis in Brain Ischemia flow grading system as persistent arterial occlusion, reocclusion or complete recanalization. Complete recanalization was defined as established Thrombolysis in Brain Ischemia 4 or 5 within 2 h of IV rt-PA. The patients were divided based on their current use of AP agents. Comparisons were made between the different groups based on recanalziation rate, reocclusion and good long-term outcome (mRS ≤2) using χ² test. Multiple regression analysis was used to identify AP use as a predictor for recanalization and outcome including symptomatic intracranial hemorrhage after controlling for age, baseline NIHSS score, time to treatment, previous vascular event, hypertension and diabetes mellitus. Results: Two hundred and eighty-four patients were included; 154 (54%) males, 130 (46%) females, with a mean age of 69.5 ± 13 years. The median baseline NIHSS score was 16 ± 5. The median time to TCD examination was 131 ± 38 min from symptom onset. The median time to IV rt-PA was 140 ± 34 min. One hundred eighty patients were not on AP prior to their stroke, 76 were on aspirin, 15 were on clopidogrel, 2 were on aspirin-dipyridamole combination, 2 were on both aspirin and clopidogrel, and 9 patients on subtherapeutic coumadin. In patients who were naïve to AP, 68/178 (38.2%) had complete recanalization, whereas in the AP group, 25/91 (28%) had complete recanalization. Patients on aspirin alone had a lower recanalization rate (16/72) as compared to those not on AP (22 vs. 39%) (p = 0.017), while those on clopidogrel had higher rates of complete recanalization (9/19, 60%). There was no difference in the rate of symptomatic intracranial hemorrhages in patients on AP agents as compared to those not on AP (9/180, 5% vs. 9/95, 9.5%) (p = 0.13). A good long-term outcome (mRS ≤2) was achieved in 85/160 (53%) of the patients naïve to AP and in 33/84 (39%) of the patients on AP (p = 0.035). In multiple regression, AP use was not a predictor of either recanalization rate (p = 0.057) or good outcome (p = 0.27). Conclusions: No correlation was found between AP use and recanalization rate and good outcome in patients with acute stroke who received IV rt-PA treatment. Prior AP use should not defer patients from receiving IV rt-PA treatment in an acute stroke setting.

Scientific Rationale for the Inclusion and Exclusion Criteria for Intravenous Alteplase in Acute Ischemic Stroke

“…Two relatively small multicenter registries and several single-center case series have shown widely varied rates of sICH (0%-36%) in patients taking warfarin with subtherapeutic INR at the time of thrombolysis. 157,177,[179][180][181][182][183][184][185][186] In 2 meta-analyses, the larger of which included 284 patients, the OR for sICH was increased for warfarin-treated patients (OR, 2.6; 95% CI, 1.1-5.9; and aOR, 4.1; 95% CI, 1-16.1), but both of these analyses were not adjusted for potential confounders. 184,187 Data from 2 large registries (GWTG and Safe Implementation of Thrombolysis in Stroke-International Stroke Thrombolysis Register [SITS-ISTR]) indicate that although patients on warfarin do have higher crude rates of sICH than those not taking warfarin, when confounders such as stroke severity, older age, and comorbidities are considered, warfarin treatment with subtherapeutic INR does not independently increase the risk of sICH.…”

“…6,54,[447][448][449][450] A secondary analysis of the Combined Lysis of Thrombus in Brain Ischemia Using Transcranial Ultrasound and Systemic TPA (CLOTBUST) trial of patients with MCA occlusions found that recanalization rates were not different in prestroke aspirin users compared with nonusers. 181 Avoidance of antiplatelet drug use for 24 hours after alteplase was specified in the protocols of the 2 NINDS trials, the ECASS III trial, and the IST-3 trial. The FDA package label for alteplase cites this trial protocol stipulation and adds that the safety of antiplatelet drug use within 24 hours is unknown.…”

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

“…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).…”

Early Deterioration After Thrombolysis Plus Aspirin in Acute Stroke

“…10 Hence, from this hypothesis-testing analysis, there is no reason to assume that aspirin early after IVT has a compensatory antithrombotic effect in the acute phase. Because only 2 small transcranial Doppler studies investigated the effect of prior antiplatelet therapy on recanalization after IVT showing conflicting results, 11,12 more studies are needed to further unravel the effects of antiplatelet therapy in combination with IVT. Stroke October 2014…”