salicylates and Stroke

Stroke is a leading cause of death worldwide and the first cause of disability in the Western world. Over the last 20 years, antiplatelet agents have reduced overall stroke rates in primary and secondary prevention in men. However, this has not been the case for women. In this narrative review, the most widely used antiplatelet therapies for primary and secondary prevention in stroke, excluding cardioembolic stroke, will be outlined. First, the largest randomised controlled trials will be analysed as well as the enrolment percentages of women. Second, analyses on sex-interaction effects in each study will be examined. Moreover, the Authors will discuss the need to develop targeted antiplatelet therapies specifically for women. Based on current results, the most randomised clinical trials and meta-analyses on antiplatelet agents in cerebrovascular disease have not performed sub-analyses on sex-related differences and this is mainly because women were underrepresented. Despite this, antiplatelet agents are considered to be equally effective for both sexes in primary and secondary stroke prevention. Finally, aspirin is the most widely studied antiplatelet in women and has been shown to provide greater benefit for women as primary prevention of ischemic stroke without a significant increased risk in haemorrhage.

Topics: Aspirin; Clopidogrel; Dipyridamole; Drug Therapy, Combination; Female; Humans; Naphthalenes; Platelet Aggregation Inhibitors; Primary Prevention; Propionates; Salicylates; Secondary Prevention; Sex Factors; Stroke; Ticlopidine

Excess activation of ionotropic glutamate receptors, primarily N-methyl-D-aspartate (NMDA) receptors and free radicals, evoke nerve cell death following hypoxic-ischemic brain injury in various animal models. However, clinical trials in stroke patients using NMDA receptor antagonists have failed to show efficacy primarily due to the limited therapeutic time window for neuroprotection and a narrow therapeutic index. In comparison, antioxidants prolonged the time window for neuroprotection in animal models of ischemic stroke and showed greater therapeutic potential in clinical trials for ischemic stroke. Excess activation of NMDA receptors and free radicals mediate the two separate pathways of nerve cell death in stroke and a safe and multifunctional drug that can block both routes in the brain will likely provide a better therapeutic outcome in patients with stroke. Derivatives of the lead structures of sulfasalazine and aspirin have led to the discovery of a new molecule, Neu2000, that has demonstrated excellent neuroprotection against NMDA- and free radical-induced cell death. Neu2000 is an NR2B-selective, moderate NMDA receptor antagonist with potent cell-permeable, spin trapping antioxidant action even at nanomolar concentrations. Nonclinical and human phase I studies demonstrated that Neu2000 can be translated to treat patients with stroke with better efficacy and therapeutic time window.

Topics: Animals; Antioxidants; Benzoates; Brain Ischemia; Drug Delivery Systems; Fluorobenzenes; Humans; meta-Aminobenzoates; Neuroprotective Agents; Receptors, N-Methyl-D-Aspartate; Salicylates; Spin Trapping; Stroke; Time Factors

Triflusal is a derivative of salicylic acid with a well-established platelet aggregation inhibitory profile. Its pharmacokinetic and pharmacodynamic properties differ, however, somewhat from those of acetylsalicylic acid. A number of recent experimental and clinical studies have shown that triflusal is a potentially useful choice in the treatment and prophylaxis of brain ischemia because of its antithrombogenic as well as neuroprotective effects. Its antithrombogenic effect has been demonstrated at the clinical as well as at the experimental level, while its neuroprotective effect has been shown only in experimental models. The drug interferes with thrombogenesis by inhibiting thromboxane synthesis and increasing the levels of cAMP and nitric oxide. Its neuroprotective action is the result of its antioxidant and antiinflammatory effects in brain tissue. From a clinical standpoint triflusal is similar in efficacy to acetylsalicylic acid in preventing stroke, but has less adverse effects, especially it is less likely to cause bleeding. Because of its pharmacodynamic properties and lower rate of adverse reactions, triflusal may be a useful alternative to acetylsalicylic acid in the prevention of stroke.

Topics: Animals; Biological Availability; Clinical Trials as Topic; Female; Humans; Male; Neuroprotective Agents; Platelet Aggregation Inhibitors; Salicylates; Stroke; Tissue Distribution

Stroke is the third most common cause of death in the US. Primary prevention of stroke can be achieved by control of risk factors including hypertension, diabetes mellitus, elevated cholesterol levels and smoking. Approximately one-third of all ischaemic strokes occur in patients with a history of stroke or transient ischaemic attack (TIA). The mainstay of secondary prevention of ischaemic stroke is the addition of medical therapy with antithrombotic agents to control the risk factors for stroke. Antithrombotic therapy is associated with significant medical complications, particularly bleeding.Low-dose aspirin (acetylsalicylic acid) has been shown to be as effective as high-dose aspirin in the prevention of stroke, with fewer adverse bleeding events. Aspirin has been shown to be as effective as warfarin in the prevention of noncardioembolic ischaemic stroke, with significantly fewer bleeding complications. Ticlopidine may be more effective in preventing stroke than aspirin, but is associated with unacceptable haematological complications. Clopidogrel may have some benefit over aspirin in preventing myocardial infarction, but has not been shown to be superior to aspirin in the prevention of stroke. The combination of clopidogrel and aspirin may be more effective than aspirin alone in acute coronary syndromes, but the incidence of adverse bleeding is significantly higher. Furthermore, the combination of aspirin with clopidogrel has not been shown to be more effective for prevention of recurrent stroke than clopidogrel alone, while the rate of bleeding complications was significantly higher with combination therapy. The combination of aspirin and extended-release dipyridamole has been demonstrated to be more effective than aspirin alone, with the same rate of adverse bleeding complications as low-dose aspirin. When selecting the appropriate antithrombotic agent for secondary prevention of stroke, the adverse event profile of the drug must be taken into account when assessing the overall efficacy of the treatment plan.

Topics: Anticoagulants; Aspirin; Clopidogrel; Dipyridamole; Drug Interactions; Drug Therapy, Combination; Humans; Platelet Aggregation Inhibitors; Salicylates; Stroke; Ticlopidine; Warfarin

Aspirin is the standard treatment for secondary prevention of stroke and other vascular events. Several studies suggest that triflusal may have a better safety profile.. To determine in people at high risk of vascular events whether triflusal is an effective and safe treatment for primary and secondary prevention of serious vascular events.. We searched the trials registers of the following Cochrane Review Groups: Stroke Group (last searched October 2004), Heart Group, Peripheral Vascular Diseases Group and Metabolic and Endocrine Disorders Group (last searched May 2003). In addition, we searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 2, 2003), MEDLINE (1977 to 2003) and EMBASE (1980 to 2003). We searched reference lists and contacted researchers in the field, authors of relevant trials and the drug manufacturer.. Randomised and quasi-randomised studies comparing triflusal with placebo or aspirin in people at high risk of vascular events.. Two authors independently assessed trial quality and extracted data. The primary outcome was a serious vascular event (non-fatal acute myocardial infarction (AMI), non-fatal ischemic or hemorrhagic stroke, or vascular death). Other efficacy and safety measures collected were frequency of different vascular events, adverse events, minor and major hemorrhages.. (1) Aspirin versus triflusal: five studies enrolled patients with stroke or transient ischemic attack (TIA) (4 trials; 2944 patients; followed for 6 to 47 months) or AMI (one trial; 2275 patients; followed for 35 days). Entry criteria were similar within each subgroup of patients. Patient groups were appropriately selected and well matched. The primary outcome in all trials was a composite outcome of vascular events. Trials had no important bias except in one study (217 patients). For the primary outcome of a serious vascular event there was no significant difference between triflusal and aspirin; the odds ratio (OR) was 1.04 (95% confidence interval (CI) 0.87 to 1.23). Significant differences were found for frequency of hemorrhages, both minor (OR 1.60, 95% CI 1.31 to 1.95) and major (OR 2.34, 95% CI 1.58 to 3.46) and for non-hemorrhagic gastrointestinal adverse events (OR 0.84, 95% CI 0.75 to 0.95). Sensitivity analysis of well versus poorly allocated trials showed no significant differences. (2) Triflusal versus placebo: two trials enrolled patients with unstable angina (281 patients) or peripheral arteriopathy (122 patients), who were followed for 6 months. Triflusal was associated with a reduction in serious vascular events (OR 2.29, 95% CI 1.01 to 5.19; OR greater than 1 favours triflusal) and with a higher frequency of adverse events (OR 1.68, 95% CI 1.00 to 2.80).. No significant differences were found between triflusal and aspirin for secondary prevention of serious vascular events in patients with stroke or TIA and AMI. However, our review cannot exclude moderate differences in efficacy. Triflusal was associated with a lower risk of hemorrhagic complications.

Topics: Aspirin; Humans; Ischemic Attack, Transient; Myocardial Infarction; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Risk Factors; Salicylates; Stroke

Patients experiencing stroke or transient ischemic attack (TIA) are at high risk for recurrent (secondary) strokes, which comprise 29% of all strokes in the United States. Current recommendations for prevention of secondary stroke from the American College of Chest Physicians (ACCP) call for the broad use of platelet antiaggregation (antiplatelet) agents for patients with a history of noncardioembolic stroke or TIA. Five agents--aspirin, ticlopidine, clopidogrel, extended-release dipyridamole (ER-DP), and triflusal--have demonstrated efficacy in large-scale clinical studies in the prevention of recurrent vascular events and/or stroke in patients with a history of stroke. The results of the following studies are reviewed and compared: the Swedish Aspirin Low-Dose Trial (SALT), the United Kingdom Transient Ischaemic Attack (UK-TIA) Aspirin Trial, Dutch Transient Ischemic Attack (Dutch TIA) study (aspirin), the Canadian American Ticlopidine Study (CATS), the Ticlopidine Aspirin Stroke Study (TASS), the African American Antiplatelet Stroke Prevention Study (AAASPS) (ticlopidine), the Clopidogrel versus Aspirin in Patients at Risk of Recurrent Ischemic Events (CAPRIE) trial, the Management of Atherothrombosis With Clopidogrel in High-Risk Patients study (MATCH) (clopidogrel), the second European Stroke Prevention Study (ESPS2) (aspirin plus ER-DP), and the Triflusal versus Aspirin in Cerebral Infarction Prevention (TACIP) study. In comparative monotherapy studies of patients with previous stroke, ticlopidine demonstrates statistically significant improved efficacy over aspirin, and clopidogrel demonstrates nonsignificant slight improvement over aspirin for the prevention of ischemic cardiac and cerebrovascular events; however, the adverse event profile of ticlopidine (including rash, diarrhea, and neutropenia) will probably limit its long-term use. Among combination approaches, only aspirin plus ER-DP has demonstrated statistically significant, clinically meaningful additive benefit over monotherapy with each agent. Clopidogrel plus aspirin did not significantly improve preventive efficacy and increased the risk of serious side effects, including life-threatening bleeding episodes. The 15,500-patient PRoFESS (the Prevention Regimen for Effectively Avoiding Second Strokes) study, with results expected in 2008, will directly compare aspirin plus ER-DP with clopidogrel monotherapy for the prevention of recurrent stroke and should provide statistically robust esti

Topics: Aspirin; Clopidogrel; Dipyridamole; Humans; Platelet Aggregation Inhibitors; Recurrence; Salicylates; Stroke; Ticlopidine

Triflusal has demonstrated an efficacy similar to aspirin in the prevention of vascular events in patients with acute myocardial infarction (ΜΙ) and ischaemic stroke but with less bleeding events.. We performed a randomised, multicentre, phase 4 clinical trial to compare the clinical efficacy and safety of triflusal versus aspirin, administered for 12 months in patients eligible to receive a cyclooxygenase-1 (COX-1) inhibitor.. Patients with stable coronary artery disease or with a history of non-cardioembolic ischaemic stroke were randomly assigned to receive either triflusal 300 mg twice or 600 mg once daily or aspirin 100 mg once daily for 12 months. The primary efficacy endpoint was the composite of: (a) ΜΙ, (b) stroke (ischaemic or haemorrhagic), or, (c) death from vascular causes for the entire follow-up period. The primary safety endpoints were the rate of bleeding events as defined by Bleeding Academic Research Consortium (BARC) criteria.. At 12-month follow-up, an equivalent result was revealed between the triflusal (n=559) and aspirin (n=560) in primary efficacy endpoint. Specifically, the combined efficacy outcome rate (i.e. MI, stroke or death from vascular causes) difference was equal to -1.3% (95% confidence interval -1.1 to 3.5) and lied within the a-priori defined equivalence interval (p<0.001). Regarding the primary safety endpoints, patients on triflusal treatment were 50% less likely to develop bleeding events according to the BARC criteria, and especially any clinically overt sign of haemorrhage that requires diagnostic studies, hospitalisation or special treatment (BARC type 2).. The efficacy of triflusal in the secondary prevention of vascular events is similar to aspirin when administered for 12 months. Importantly, triflusal significantly reduced the incidence of ΜΙ and showed a better safety profile compared with aspirin. (ASpirin versus Triflusal for Event Reduction In Atherothrombosis Secondary prevention, ASTERIAS trial; Clinical Trials.gov Identifier: NCT02616497).

Topics: Aged; Aspirin; Brain Ischemia; Coronary Artery Disease; Cyclooxygenase Inhibitors; Female; Greece; Hemorrhage; Humans; Intracranial Embolism; Male; Middle Aged; Myocardial Infarction; Platelet Aggregation Inhibitors; Recurrence; Risk Factors; Salicylates; Secondary Prevention; Stroke; Time Factors; Treatment Outcome

The potential of neuroprotective agents should be revisited in the era of endovascular thrombectomy (EVT) for acute large-artery occlusion because their preclinical effects have been optimized for ischemia and reperfusion injury. Neu2000, a derivative of sulfasalazine, is a multi-target neuroprotectant. It selectively blocks N-methyl-D-aspartate receptors and scavenges for free radicals. This trial aimed to determine whether neuroprotectant administration before EVT is safe and leads to a more favorable outcome.. This trial is a phase-II, multicenter, three-arm, randomized, double-blinded, placebo-controlled, blinded-endpoint drug trial that enrolled participants aged ≥ 19 years undergoing an EVT attempt less than 8 h from symptom onset, with baseline National Institutes of Health Stroke Scale (NIHSS) score ≥ 8, Alberta Stroke Program Early CT score ≥ 6, evidence of large-artery occlusion, and at least moderate collaterals on computed tomography angiography. EVT-attempted patients are randomized into control, low-dose (2.75 g), and high-dose (5.25 g) Neu2000KWL over 5 days. Seventy participants per group are enrolled for 90% power, assuming that the treatment group has a 28.4% higher proportion of participants with functional independence than the placebo group. The primary outcome, based on intention-to-treat criteria is the improvement of modified Rankin Scale (mRS) scores at 3 months using a dichotomized model. Safety outcomes include symptomatic intracranial hemorrhage within 5 days. Secondary outcomes are distributional change of mRS, mean differences in NIHSS score, proportion of NIHSS score 0-2, and Barthel Index > 90 at 1 and 4 weeks, and 3 months.. The trial results may provide information on new therapeutic options as multi-target neuroprotection might mitigate reperfusion injury in patients with acute ischemic stroke before EVT.. ClinicalTrials.gov, ID: NCT02831088 . Registered on 13 July 2016.

Topics: Brain Ischemia; Clinical Trials, Phase II as Topic; Disability Evaluation; Double-Blind Method; Endovascular Procedures; Fluorobenzenes; Humans; meta-Aminobenzoates; Multicenter Studies as Topic; Neuroprotective Agents; Prospective Studies; Randomized Controlled Trials as Topic; Recovery of Function; Republic of Korea; Salicylates; Stroke; Thrombectomy; Time Factors; Treatment Outcome

The antiplatelet effect of clopidogrel is reportedly influenced by cytochrome P450 2C19 (CYP2C19) polymorphisms. However, there is no data concerning the relationship between stroke recurrence and CYP2C19 polymorphisms in patients treated with clopidogrel for secondary prevention of ischemic stroke. Triflusal may be an alternative therapy for clopidogrel in patients with poor genotype. The Comparison of Triflusal and Clopidogrel Effects in Secondary Prevention of Stroke Based on Cytochrome P450 2C19 Genotyping (MAESTRO) study will investigate the effect of antiplatelet agents based on CYP2C19 polymorphisms in secondary prevention of ischemic stroke.. Assuming that 55% of patients belong to the poor genotype group, the required sample size is 1080 patients with at least 24 months of follow-up. This study is designed as a prospective, multicenter, randomized, parallel-group, open-label, and blind genotype trial. Patients who experience their first non-cardiogenic ischemic stroke within 30 days prior to screening are eligible. Patients received 300 mg triflusal twice a day or 75 mg clopidogrel once daily during the trial. The study is registered with ClinicalTrials.gov (NCT01174693).. The primary outcome is recurrent ischemic stroke or hemorrhagic stroke. Secondary outcomes consist of composite major vascular events including stroke, myocardial infarction, coronary revascularization, or vascular death.. Personalized medicine may be essential for patients according to individual drug metabolism abilities. MAESTRO is the first prospective study designed to evaluate the effect of CYP2C19 polymorphism in secondary stroke prevention and will resolve several questions regarding preventive antiplatelet agents for recurrent stroke.

Topics: Brain Ischemia; Cerebral Hemorrhage; Chemoprevention; Clopidogrel; Cytochrome P-450 CYP2C19; Follow-Up Studies; Genotype; Humans; Pharmacogenomic Variants; Platelet Aggregation Inhibitors; Recurrence; Salicylates; Secondary Prevention; Single-Blind Method; Stroke; Ticlopidine; Treatment Outcome

The purpose of this study is to identify factors which predict adherence in stroke survivors.. This is a longitudinal study where 180 stroke survivors were assessed 1 year after their first ischaemic stroke. The relationship between adherence and illness and medication beliefs was tested at baseline (time 1) and again 5-6 weeks later (time 2).. The main outcome measures used in this study are Medication Adherence Report Scale and urinary salicylate levels.. Four variables predicted time 1 poor adherence: (1) younger age, (2) increased specific concerns about medications, (3) reduced cognitive functioning and (4) low perceived benefit of medication. Three out of these four variables were again predictive of time 2 adherence and accounted for 24% of the variance: (1) younger age, (2) increased specific concerns about medications and (3) low perceived benefit of medication. The urinary salicylate assay failed to differentiate between patients taking and not taking aspirin.. Interventions to improve adherence should target patients' beliefs about their medication.

Topics: Age Factors; Aged; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Attitude to Health; Brain Ischemia; Cognition; Female; Humans; Longitudinal Studies; Male; Medication Adherence; Psychiatric Status Rating Scales; Salicylates; Secondary Prevention; Severity of Illness Index; Stroke

Triflusal is a 4-fluoromethyl derivative of salicylic acid used for secondary prevention of ischemic stroke. Recent experimental data (permanent middle cerebral artery occlusion in rats) have shown a possible role of triflusal in neuroprotection through inhibition of inflammatory pathways.. To explore whether triflusal may modulate those pathways in human stroke, evolution of several inflammation markers (pro-inflammatory, adhesion molecules, chemokines, metalloproteinases, apoptosis and angiogenesis-related biomarkers) and neurological outcome were evaluated at baseline, and at days 1, 3, 7 and 90 in a pilot study in which 30 patients with acute ischemic stroke were randomly allocated to receive triflusal or aspirin.. An increase in IL-6 level was found in the aspirin group when compared to the triflusal group at the third and seventh day (p < 0.05). FGF-basic level was significantly increased at days 1 and 90 in the triflusal group (p = 0.040). The triflusal group also had higher levels of MIP-1alpha and MIP-1beta (p < 0.05) at day 1. Also among triflusal-treated patients, MCP-1 and TARC levels were increased as compared with the aspirin group at day 90 (p < 0.05). Interestingly, some of those markers modified by triflusal (MCP-1 and IL-6) were associated with neurological outcome: higher MCP-1 measured at day 3 among patients who improve at day 7 [462.3 (419.2-735.2) vs. 285 (242.1-428.2), p < 0.05], and lower levels of IL-6 at day 3 among patients who improve at day 90 [24.8 (5.6-77.3) vs. 5.4 (2.0-13.8), p < 0.05].. Triflusal modulates additional mechanisms to those of aspirin [pro-inflammatory (IL-6) and chemokine (MIP-1 and MCP-1) pathways] that could participate in the ischemic damage process following human acute stroke.

Topics: Aged; Aged, 80 and over; Anti-Inflammatory Agents; Aspirin; Biomarkers; Brain Ischemia; Female; Humans; Inflammation Mediators; Logistic Models; Male; Middle Aged; Neuroprotective Agents; Pilot Projects; Platelet Aggregation Inhibitors; Prospective Studies; Salicylates; Stroke; Time Factors; Treatment Outcome

Triflusal is an antiplatelet agent that has shown clinical advantages when compared with aspirin in the secondary prevention of vascular events. TAPIRSS (Triflusal versus Aspirin for Prevention of Infarction: a Randomized Stroke Study) explored the efficacy and safety of triflusal in the secondary prevention of stroke in a Latin American homogeneous population with the ultimate aim of preparing for a larger trial in the same setting.. A double-blind, multicenter, randomized, pilot trial was conducted in Buenos Aires, Argentina, from October 1996 to November 1999. The study sample was 431 patients, randomized to receive aspirin 325 mg daily or triflusal 600 mg daily for a mean of 586 days. All patients had experienced either an ischemic stroke or TIA within 6 months from enrollment. Data from 429 patients were analyzed.. No differences were observed in the primary endpoint that combined the incidence of vascular death, cerebral ischemic infarction, nonfatal myocardial infarction, or major hemorrhage (aspirin 13.9%, triflusal 12.7%; odds ratio [OR] 1.11, 95% CI 0.64 to 1.94) or in the individual analysis of each component of the primary endpoint. In a post hoc analysis, the overall incidence of major and minor hemorrhagic events was significantly lower in triflusal-treated patients (aspirin 8.3%, triflusal 2.8%; OR 3.13, 95% CI 1.22 to 8.06).. This pilot trial has not found differences between triflusal and aspirin in the prevention of vascular complications after TIA or ischemic stroke, although given the wide CI, potentially important group differences could not be ruled out. Triflusal may be associated with a lower risk of hemorrhagic complications. A larger, prospective clinical trial is necessary to verify these results.

Topics: Aged; Aspirin; Cerebral Infarction; Double-Blind Method; Female; Follow-Up Studies; Humans; Ischemic Attack, Transient; Male; Middle Aged; Odds Ratio; Pilot Projects; Platelet Aggregation Inhibitors; Salicylates; Secondary Prevention; Stroke; Survival Analysis; Treatment Outcome

The efficacy of the antiplatelet agent triflusal for prevention of vascular events after stroke has been reported in a pilot study. However, there is a need to confirm those results in a larger study.. We performed a randomized, double-blind, multicenter study to test the efficacy of triflusal (600 mg/d) versus aspirin (325 mg/d) for prevention of vascular events in patients with stroke or transient ischemic attack (Triflusal versus Aspirin in Cerebral Infarction Prevention [TACIP]). We assessed a combined end point (incidence of nonfatal ischemic stroke, nonfatal acute myocardial infarction, or vascular death) as well as the incidence of these events separately and the incidence of major hemorrhage.. Of 2113 patients, 1058 received triflusal and 1055 aspirin. The mean follow-up period was 30.1 months. The incidence of combined end point (13.1% for triflusal, 12.4% for aspirin) as well the survival analysis (hazard ratio [HR] for triflusal versus aspirin, 1.09; 95% CI, 0.85 to 1.38) showed no differences between groups. The incidence of nonfatal stroke (HR, 1.09; 95% CI, 0.82 to 1.44), nonfatal acute myocardial infarction (HR, 0.95; 95% CI, 0.46 to 1.98,) and vascular death (HR, 1.22; 95% CI, 0.75 to 1.96) was also similar. A significantly higher incidence of major hemorrhages in the aspirin group was recorded (HR, 0.48; 95% CI, 0.28 to 0.82). The overall incidence of hemorrhage was significantly lower in the triflusal group (16.7% versus 25.2%) (odds ratio, 0.76; 95% CI, 0.67 to 0.86; P<0.001).. This study failed to show significantly superior efficacy of triflusal over aspirin in the long-term prevention of vascular events after stroke, but triflusal was associated with a significantly lower rate of hemorrhagic complications.

Topics: Aspirin; Cardiovascular Diseases; Cerebral Infarction; Double-Blind Method; Female; Hemorrhage; Humans; Incidence; Male; Middle Aged; Myocardial Infarction; Platelet Aggregation Inhibitors; Salicylates; Secondary Prevention; Stroke; Survival Analysis

BACKGROUND Over-the-counter medications that contain aspirin are widely used, and patients generally regard them as safe. However, the side effects of salicylate toxicity can be severe, and delay in the diagnosis may increase the risk of mortality. Neurologic symptoms are a common presenting feature of salicylate toxicity in the elderly, and their recognition may allow earlier diagnosis. This report is of a case of a 61-year-old woman who presented with acute focal neurologic deficit associated with salicylate toxicity and who had a previous history of stroke. CASE REPORT A 61-year-old woman presented to the Emergency Department after awakening with left-sided weakness. She had a history of ischemic stroke with an associated seizure disorder. The patient denied recent seizure, and brain magnetic resonance imaging (MRI) showed no evidence of an acute stroke. Following her arrival, she became acutely confused and complained of tinnitus, shortness of breath, and blurred vision. On direct questioning, she gave a history of excessive use of salicylate for the previous two to three weeks. Her initial serum salicylate level was significantly increased at 78.1 mg/dl (upper therapeutic limit, 19.9 mg/dl). She recovered completely following treatment with oral activated charcoal, intravenous sodium bicarbonate, and potassium replacement. CONCLUSIONS This case demonstrates that physicians should consider salicylate toxicity as a possible cause of exacerbation of neurological deficit in elderly patients.

Topics: Charcoal; Delirium; Female; Humans; Middle Aged; Neurologic Examination; Neurotoxicity Syndromes; Paresis; Potassium; Salicylates; Sodium Bicarbonate; Stroke; Tinnitus

Postischemic brain damage in stroke is proceded with complicated pathological events, and so multimodal drug treatments may offer better therapeutic means for improving clinical outcomes. Here, we report robust neuroprotective effects of a novel compound, 2-((2-oxopropanoyl)oxy)-4-(trifluoromethyl)benzoic acid (OPTBA), a 2-hydroxy-4-trifluoromethyl benzoic acid (HTB, a metabolite of triflusal)-pyruvate ester. Intravenous administration of OPTBA (5 mg/kg) 3 or 6 h after middle cerebral artery occlusion (MCAO) in Sprague-Dawley rats reduced infarct volumes to 38.5 ± 11.4% and 46.5 ± 15.3%, respectively, of that of MCAO controls, and ameliorated motor impairment and neurological deficits. Importantly, neuroprotective effects of OPTBA were far greater than those afforded by combined treatment of HTB and pyruvate. Furthermore, OPTBA suppressed microglial activation and proinflammatory cytokine inductions more effectively than HTB/pyruvate co-treatment in the postischemic brain and LPS-treated cortical slice cultures and also attenuated NMDA-induced neuronal death in hippocampal slice cultures. LC-MS analysis demonstrated that OPTBA was hydrolyzed to HTB and pyruvate with a t1/2 of 38.6 min in blood and 7.2 and 2.4 h in cortex and striatum, respectively, and HTB was maintained for more than 24 h both in blood and brain tissue. Together these results indicate OPTBA acts directly and via its hydrolysis products, thus acting as a multimodal neuroprotectant in the postischemic brain.

Topics: Animals; Benzoates; Blood-Brain Barrier; Brain Ischemia; Cytokines; Disease Models, Animal; Hydrolysis; Male; Neuroprotective Agents; Rats; Rats, Sprague-Dawley; Salicylates; Stroke

Topics: Aspirin; Carotid Arteries; Clinical Trials as Topic; Endarterectomy, Carotid; Guidelines as Topic; Humans; Ischemic Attack, Transient; Platelet Aggregation Inhibitors; Salicylates; Stents; Stroke

Clinical data has shown that stroke exacerbates dementia in Alzheimer's disease (AD) patients. Previous work, combining rat models of AD and stroke have shown that neuroinflammation may be the common mediator between AD and stroke toxicity. This study examined the effects of triflusal (2-acetoxy-4-trifluoromethylbenzoic acid) in APP(23) transgenic mice receiving strokes. Six month-old APP(23) mice over-expressing mutant human amyloid precursor protein (APP) were used to model AD in this study. Unilateral injections of a potent vasoconstrictor, endothelin-1, into the striatum were used to mimic small lacunar infarcts. Immunohistochemical analysis was performed to examine AD-like pathology and inflammatory correlates of stroke and AD. APP(23) mice showed increases in AD-like pathology and inflammatory markers of AD in the cortex and hippocampus. Endothelin-induced ischemia triggered an inflammatory response along with increases in AD pathological markers in the region of the infarct. Triflusal reduced inflammation surrounding the endothelin-induced infarct only. At the dose used, anti-inflammatory treatment may be beneficial in reducing the AD and inflammatory correlates of stroke in a combined AD-stroke mouse model.

Topics: Administration, Oral; Alzheimer Disease; Amyloid beta-Protein Precursor; Animals; Antigens, CD; Brain Ischemia; Disease Models, Animal; Endothelin-1; Humans; Inflammation; Mice; Mice, Inbred C57BL; Mice, Transgenic; NF-kappa B; Platelet Aggregation Inhibitors; Salicylates; Stroke; tau Proteins; Tumor Necrosis Factor-alpha

Topics: Aspirin; Cerebral Infarction; Humans; Pilot Projects; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Salicylates; Stroke; Treatment Outcome

Topics: Aspirin; Clinical Trials as Topic; Drug Therapy, Combination; Fibrinolytic Agents; Forecasting; Humans; Platelet Aggregation Inhibitors; Salicylates; Stroke

Topics: Arthritis, Rheumatoid; Echocardiography, Transesophageal; Female; Humans; Middle Aged; Mitral Valve; Mitral Valve Prolapse; Platelet Aggregation Inhibitors; Recurrence; Salicylates; Stroke; Treatment Outcome