Safety of Intravenous Thrombolysis for Acute Ischemic Stroke in Patients Receiving Antiplatelet Therapy at Stroke Onset (original) (raw)
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Intravenous thrombolysis for acute ischemic stroke patients presenting with mild symptoms
2013
Background-The safety and long-term outcome of systemic thrombolysis in patients receiving antiplatelet medications remain subjects of great clinical significance. The objective of this meta-analysis was to determine how prestroke antiplatelet therapy affects the risks and benefits of intravenous thrombolysis in patients with acute ischemic stroke. Methods and Results-A dual-reviewer search was conducted in PubMed and EMBASE databases through November 2015, from which 19 studies involving a total of 108 588 patients with acute ischemic stroke were identified based on preset inclusion criteria. Information on study designs, patient characteristics, exposures, outcomes, and adjusting confounders was extracted, and estimates were combined by using random-effects models. The pooled crude estimates suggested that taking long-term antiplatelet medications was associated with higher odds of symptomatic intracranial hemorrhage (odds ratio [OR] 1.70, 95% CI 1.47-1.97) and death (OR 1.46, 95% CI 1.22-1.75) and lower odds of favorable functional outcomes (OR 0.86, 95% CI 0.80-0.93). However, the combined confounder-adjusted results only confirmed a relatively weak positive association between prior antiplatelet therapy and symptomatic intracranial hemorrhage (OR 1.21, 95% CI 1.02-1.44) and demonstrated no significant relationship between antiplatelet therapy and the other 2 outcomes (favorable outcome OR 1.09, 95% CI 0.96-1.24; death OR 1.02, 95% CI 0.98-1.07). Subgroup analyses revealed that the associations between prestroke antiplatelet therapy and outcomes were dependent on time and antiplatelet agents. Conclusions-Patients with acute ischemic stroke receiving long-term antiplatelet medications were associated with greater risks of developing symptomatic intracranial hemorrhage after systemic thrombolysis. However, the overall independent association between prestroke antiplatelet therapy and unfavorable outcomes or mortality was insignificant.
Trials, 2010
Thrombolysis with intravenous rt-PA is currently the only approved acute therapy for ischemic stroke. Re-occlusion after initial recanalization occurs in up to 34% in patients treated with rt-PA, probably caused by platelet activation. In acute myocardial infarction, the combination of thrombolysis and antiplatelet therapy leads to a greater reduction of mortality compared to thrombolysis alone. In patients with acute ischemic stroke, several studies showed that patients already on antiplatelet treatment prior to thrombolysis had an equal or even better outcome compared to patients without prior antiplatelet treatment, despite an increased risk of intracerebral bleeding. Based on the fear of intracerebral haemorrhage, current international guidelines recommend postponing antiplatelet therapy until 24 hours after thrombolysis. Remarkably, prior use of antiplatelet therapy is not a contra-indication for thrombolysis. We hypothesize that antiplatelet therapy in combination with rt-PA t...
Journal of neurology, 2017
Since there are contradictory data regarding the association of antiplatelet pretreatment (AP) with safety and efficacy outcomes of intravenous thrombolysis (IVT) for acute ischemic stroke (AIS), we conducted a systematic review and meta-analysis of available randomized-controlled clinical trials (RCTs) to investigate the association of AP with outcomes of AIS patients treated with intravenous alteplase. The outcome events of interest included symptomatic intracranial hemorrhage (sICH), fatal ICH, complete recanalization (CR), 3-month favorable functional outcome (FFO, mRS score 0-1), 3-month functional independence (FI, mRS score 0-2), and mortality. The corresponding odds ratios (ORs) were calculated for all the outcome events using random-effects model. The adjusted age and admission NIHSS OR (ORadjusted) were also estimated for all available outcomes. We included 7 RCTs (4376 patients, 33.7% with AP). In unadjusted analyses, AP was associated with higher likelihood of sICH (OR =...
Cerebrovascular Diseases, 2012
Background: Information is scare regarding the safety of intravenous thrombolysis in patients under anticoagulant treatment, given that this is an exclusion criterion in clinical trials. We analyzed the risk of hemorrhagic complications following thrombolysis in patients under treatment with low-molecular-weight heparins (LMWH) and oral anticoagulants (OA). Methods: In a multicentered prospective study of consecutive acute stroke patients treated with intravenous alteplase we recorded age, gender, baseline NIHSS score, treatment delay, risk factors, etiology and previous therapy. The neurological progress (National Institutes of Health Stroke Scale at 7 days) and functional evolution at 3 months (modified Rankin Scale score), mortality and symptomatic intracerebral hemorrhage (SICH) were compared between patients with LMWH or OA and those without prior anticoagulant therapy. Results: Of the 1,482 patients, 21 (1.4%) had received LMWH and 70 (4.7%) OA (international normalized ratio,...
Trends in Usage of Alternative Antiplatelet Therapy After Stroke and Transient Ischemic Attack
Stroke, 2008
The effects of alternative antiplatelet agents such as clopidogrel and dipyridamole have been studied in clinical trials and heavily marketed. Because public data on their usage are limited, we examined trends in their prescription after stroke and transient ischemic attack to assess the impact of marketing and trial results. Between 2001 and 2005, 85 US hospitals prospectively enrolled all patients admitted with ischemic stroke or transient ischemic attack into a registry designed for quality improvement (Ethos). Data on rates of antiplatelet medication usage at discharge were examined over time, and trends were evaluated by the Mantel-Haenszel test. Among 18 020 patients included during the 4-year period, 89% were discharged on antithrombotic medication. Between the first quarter of 2001 and the first quarter of 2004, prescription of clopidogrel-aspirin doubled (P<0.0001 for trend), coincident with publication of results from CURE and CREDO showing efficacy in patients with acute coronary syndromes. Monotherapy with aspirin or clopidogrel decreased concomitantly, and use of dipyridamole-aspirin remained constant. After an increased bleeding risk was reported in the clopidogrel-aspirin arm of the MATCH trial, use of the combination decreased sharply from 31.5% in the first quarter of 2004 to 12.8% in the first quarter of 2005 (P<0.0001), while an increase was seen in the use of clopidogrel alone (7.6% to 12.8%, P=0.03) and dipyridamole-aspirin (7.4% to 20.2%, P<0.0001). Clopidogrel and dipyridamole-aspirin are used frequently after stroke or transient ischemic attack. Use of clopidogrel-aspirin was common in patients with recent ischemic stroke before the publication of MATCH, after which rates dramatically declined and use of dipyridamole-aspirin and clopidogrel alone increased.
Academic Emergency Medicine, 2013
Objectives: Intracranial hemorrhage (ICH) after acute stroke thrombolysis is associated with poor outcomes. Previous investigations of the relationship between preexisting antiplatelet use and the safety of intravenous (IV) thrombolysis have been limited by low event rates. The objective of this study was to determine whether preexisting antiplatelet therapy increased the risk of ICH following acute stroke thrombolysis. The primary hypothesis was that antiplatelet use would not be associated with radiographic evidence of ICH after controlling for relevant confounders. Methods: Consecutive cases of thrombolysis patients treated in the emergency department (ED) were identified using multiple methods. Retrospective data were collected from four hospitals from 1996 to 2004 and 24 other hospitals from 2007 to 2010 as part of a cluster-randomized trial. The same chart abstraction tool was used during both time periods, and data were subjected to numerous quality control checks. Hemorrhages were classified using a prespecified methodology: ICH was defined as presence of hemorrhage in radiographic interpretations of follow-up imaging (primary outcome). Symptomatic ICH (sICH) was defined as radiographic ICH with associated clinical worsening. A multivariable logistic regression model was constructed to adjust for clinical factors previously identified to be related to postthrombolysis ICH. Sensitivity analyses were conducted where the unadjusted and adjusted results from this study were combined with those of previously published external studies on this topic via meta-analytic techniques. Results: There were 830 patients included, with 47% having documented preexisting antiplatelet treatment. The mean (AE standard deviation [SD]) age was 69 (AE15) years, and the cohort was 53% male. The unadjusted proportion of patients with any ICH was 15.1% without antiplatelet use and 19.3% with antiplatelet use (absolute risk difference = 4.2%, 95% confidence interval [CI] = À1.2% to 9.6%); for sICH this was 6.1% without antiplatelet use and 9% with antiplatelet use (absolute risk difference = 3.1%, 95% CI = À1% to 6.7%). After adjusting for confounders, antiplatelet use was not significantly associated with radiographic ICH (odds ratio [OR] = 1.1, 95% CI = 0.8 to 1.7) or sICH (OR = 1.3, 95% CI = 0.7 to 2.2). In patients 81 years and older, there was a higher risk of radiographic ICH (absolute risk difference = 11.9%, 95% CI = 0.1% to 23.6%). The meta-analyses combined the findings of this investigation with previous similar work and found increased unadjusted risks of radiographic ICH (absolute risk difference = 4.9%, 95% CI = 0.7% to 9%) and sICH (absolute risk difference = 4%, 95%
Health technology assessment (Winchester, England), 2018
Two antiplatelet agents are better than one for preventing recurrent stroke after acute ischaemic stroke or transient ischaemic attack (TIA). Therefore, intensive treatment with three agents might be better still, providing it does not cause undue bleeding. To compare the safety and efficacy of intensive therapy with guideline antiplatelet therapy for acute ischaemic stroke and TIA. International prospective randomised open-label blinded end-point parallel-group superiority clinical trial. Acute hospitals at 106 sites in four countries. Patients > 50 years of age with acute non-cardioembolic ischaemic stroke or TIA within 48 hours of ictus (stroke). Participants were allocated at random by computer to 1 month of intensive (combined aspirin, clopidogrel and dipyridamole) or guideline (combined aspirin and dipyridamole, or clopidogrel alone) antiplatelet agents, and followed for 90 days. The primary outcome was the incidence and severity of any recurrent stroke (ischaemic, haemorrh...
PloS one, 2017
Symptomatic intracerebral hemorrhage (sICH) after bridging thrombolysis for acute ischemic stroke is a devastating complication. We aimed to assess whether the additional administration of aspirin during endovascular intervention increases bleeding rates. We retrospectively compared bleeding complications and outcome in stroke patients who received bridging thrombolysis with (tPA+ASA) and without (tPA-ASA) aspirin during endovascular intervention between November 2008 and March 2014. Furthermore, we analyzed bleeding complications and outcome in antiplatelet naïve patients with those with prior or acute antiplatelet therapy. Baseline characteristics, previous medication, and dosage of rtPA did not differ between 50 tPA+ASA (39 aspirin naïve, 11 preloaded) and 181 tPA-ASA patients (p>0.05). tPA+ASA patients had more often internal carotid artery (ICA) occlusion (p<0.001), large artery disease (p<0.001) and received more often acute stenting of the ICA (p<0.001). 10/180 (5...
International journal of stroke : official journal of the International Stroke Society, 2016
The risk of recurrence following ischemic stroke or transient ischemic attack is highest immediately after the event. Antiplatelet agents are effective in reducing the risk of recurrence and two agents are superior to one in the early phase after ictus. The triple antiplatelets for reducing dependency after ischemic stroke trial was an international multicenter prospective randomized open-label blinded-endpoint trial that assessed the safety and efficacy of short-term intensive antiplatelet therapy with three agents (combined aspirin, clopidogrel and dipyridamole) as compared with guideline treatment in acute ischemic stroke or transient ischemic attack. The primary outcome was stroke recurrence and its severity, measured using the modified Rankin Scale at 90 days. Secondary outcomes included recurrent vascular events, functional measures (cognition, disability, mood, quality of life), and safety (bleeding, death, serious adverse events). Data are number (%) or mean (standard deviat...