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The Efficacy and Adverse Reaction of Bleeding of Clopidogrel plus Aspirin as Compared to Aspirin Alone after Stroke or TIA: A Systematic Review  [PDF]
Yan Huang, Man Li, Jian-Yong Li, Min Li, Yuan-Peng Xia, Ling Mao, Bo Hu
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0065754
Abstract: Background and Purpose Given the high risk of stroke after TIA (transient ischemia attack) or stroke and the adverse reaction of bleeding of antiplatelets, we undertook a meta-analysis, reviewed randomized controlled trials (RCTs) comparing aspirin plus clopidogrel with aspirin alone to determine the efficacy and adverse reaction of bleeding of the two protocols in the prevention of stroke. Methods We analyzed the incidences of stroke, bleeding and severe bleeding by using fixed-effect model or random-effect model on the basis of the result of heterogeneity test. Results Five qualified RCTs satisfied the inclusion criteria. We found that treatment with aspirin plus clopidogrel was associated with lower incidence of stroke (Risk Ratio (RR), 0.66, 95% confidence interval (CI), 0.47 to 0.93), higher incidence of bleeding (RR, 1.75, 95% CI, 1.48 to 2.05) as compared with aspirin-alone treatment. In terms of severe bleeding, no statistical difference existed between them (RR, 2.21, 95% CI, 0.25 to 19.52). Conclusion The combined use of aspirin and clopidogrel is more effective than aspirin alone for patients with previous TIA or stroke for the prevention of stroke, with risk of bleeding being higher. No statistical difference was found in severe bleeding between the two treatment protocols.
Nadroparine calcium or enoxaparine in acute coronary syndrome patients suffering renal insufficiency: The nadroparin versus enoxaparin (NaVe) study design
Enrique P Gurfinkel, Cecilia Perel, Gonzalo Pombo
Thrombosis Journal , 2004, DOI: 10.1186/1477-9560-2-6
Abstract: In such sense, anticoagulation in addition to antiplatelet inhibitor drugs became the standard of care, particularly, among high risk unstable angina patients associated with a scarce side effects.The Nadroparin calcium Versus Enoxaparin (NaVe) Study will evaluate in a head to head basis the anti Xa activity reached by nadroparine or enoxaparine, both low molecular weight heparins, in patients at high risk for ischemic episodes, and renal insufficiency to eventually be undergone to angiographic diagnosis studies, and in consequence proposing the best anticoagulant strategies for these patients before being invasively treated.Patients will be randomly assigned to one of the two groups: Group 1: thirty patients will be given with subcutaneous enoxaparine injections into the abdominal wall in a dose of 0,85 mg/kg every 12 hours for a maximum of 48 hours. A saline infusion dose will be given in between. Total number of injections: 6. Group 2:Thirty patients will be receiving subcutaneous injections into the abdominal wall in a doses of 30% less in relationship with his / her body weight every 8 hours for a maximum of 48 hours.In order to achieve the goal of the study, the antiXa activity will be measure using venous blood samples taken as follows: Group 1:*Within 3rd and 4 hour of the second doses of HBPM for enoxaparine.*Within 11 th and 12 th hour next to fourth doses of enoxaparine. Group 2: *Within 3rd and 4 th hour next to 3rd doses of HBPM for the nadroparine.*Within 7th and 8th hour next to 4th doses HBPM for the nadroparine.The primary end point is to analyze during the in-hospital stay phase the stability of the anti Xa activity within the therapeutic ranges which will be estimated between 0.5 to 1.0 IU during the first 48 hours.In the general population, mild renal impairment is associated with increases risk for coronary artery disease and stroke, suggesting that cardiovascular disease begins to develop early in the natural history of renal dysfunction[1]. Pa
Paradoxical Effect of Aspirin  [PDF]
Christian Doutremepuich,Omar Aguejouf,Vanessa Desplat,Francisco X. Eizayaga
Thrombosis , 2012, DOI: 10.1155/2012/676237
Abstract: Low-dose aspirin is an important therapeutic option in the secondary prevention of myocardial infarction (MI) and ischemic stroke, basedon its unique cost-effectiveness and widespread availability. In addition, based on the results of a number of large studies, aspirin is also widely used in the primary prevention of MI. This paper provides an update of the available data to offer greater clarity regarding the risks of aspirin with respect to hemorrhagic stroke. In the secondary prevention of cardiovascular, cerebrovascular, and ischemic events, the evidence supports that the benefits of aspirin treatment significantly outweigh the risk of a major hemorrhage. When considering whether aspirin is appropriate, the absolute therapeutic cardiovascular benefits of aspirin must be balanced with the possible risks associated with its use, being hemorrhagic stroke. Regarding these clinical facts, normal, COX 1 −/−, and COX 2 −/− mice were treated with a wide range of doses of aspirin and studied by induced hemorrhagic time. The results outlined three major conclusions: high doses of aspirin induce hemorrhage, while low doses of aspirin do not. In the absence of COX 1, ultra low doses of aspirin produce an antihemorrhagic effect not observed with intermediate doses. The absence of COX 2 induced a hemorrhagic effect that needs further research, probably originated in compensatory phenomena.
Neuroprotective Effect of a New Synthetic Aspirin-decursinol Adduct in Experimental Animal Models of Ischemic Stroke  [PDF]
Bing Chun Yan, Joon Ha Park, Bich Na Shin, Ji Hyeon Ahn, In Hye Kim, Jae-Chul Lee, Ki-Yeon Yoo, In Koo Hwang, Jung Hoon Choi, Jeong Ho Park, Yun Lyul Lee, Hong-Won Suh, Jong-Gab Jun, Young-Guen Kwon, Young-Myeong Kim, Seung-Hae Kwon, Song Her, Jin Su Kim, Byung-Hwa Hyun, Chul-Kyu Kim, Jun Hwi Cho, Choong Hyun Lee, Moo-Ho Won
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0074886
Abstract: Stroke is the second leading cause of death. Experimental animal models of cerebral ischemia are widely used for researching mechanisms of ischemic damage and developing new drugs for the prevention and treatment of stroke. The present study aimed to comparatively investigate neuroprotective effects of aspirin (ASA), decursinol (DA) and new synthetic aspirin-decursinol adduct (ASA-DA) against transient focal and global cerebral ischemic damage. We found that treatment with 20 mg/kg, not 10 mg/kg, ASA-DA protected against ischemia-induced neuronal death after transient focal and global ischemic damage, and its neuroprotective effect was much better than that of ASA or DA alone. In addition, 20 mg/kg ASA-DA treatment reduced the ischemia-induced gliosis and maintained antioxidants levels in the corresponding injury regions. In brief, ASA-DA, a new synthetic drug, dramatically protected neurons from ischemic damage, and neuroprotective effects of ASA-DA may be closely related to the attenuation of ischemia-induced gliosis and maintenance of antioxidants.
Frequency of microembolic signals in patients with acute ischemic stroke in middle cerebral artery territory treated with aspirin or clopidogrel
Mazyar Hashemilar,Mehdi Farhoudi,Samane Hosseini,Hanieh Moshayedi
Iranian Journal of Neurology , 2011,
Abstract: Background: In patients with acute stroke and middle cerebral artery (MCA) stenosis, microembolic signals (MES) can predict further cerebral ischemia. Therefore, this study was designed to evaluate the prevalence of MES by transcranial Doppler (TCD) in patients with MCA stenosis under treatment of aspirin or clopidogrel.Methods: A randomized clinical trial was performed on 40 patients with acute ischemic stroke in MCA territory. They were randomly allocated in two groups that treated with aspirin (80 mg daily) or clopidogrel (75 mg daily). Clinical and diagnostic work up was included evaluation of cerebrovascular risk factors, echocardiography, carotid color Doppler and brain imaging. TCD was performed between day 3 and 7 after symptoms onset to detect MES. All high intensity transient signals (HITS) were saved and analyzed offline.Results: Carotid stenosis was found in 13 (65%) patients of aspirin group and 12 (60%) of clopidogrel group. Four (30.8%) of aspirin group and 5 (41.7) of clopidogrel group had stenosis between 10%-50%. One patient in each group had more than 50% stenosis and the remainder had less than 10%. There was no significant difference between two groups. MES was detected in 6 (30%) of patients treated with aspirin and 4 (20%) of those treated with clopidogrel. It showed no statistically significant differences (P-value= 0.46).Conclusion: Our results indicate a similar effect of aspirin and clopidogrel on frequency of MES in patients with MCA territory ischemic stroke
Paradoxical Effect of Aspirin  [PDF]
Christian Doutremepuich,Omar Aguejouf,Vanessa Desplat,Francisco X. Eizayaga
Thrombosis , 2012, DOI: 10.1155/2012/676237
Abstract: Low-dose aspirin is an important therapeutic option in the secondary prevention of myocardial infarction (MI) and ischemic stroke, basedon its unique cost-effectiveness and widespread availability. In addition, based on the results of a number of large studies, aspirin is also widely used in the primary prevention of MI. This paper provides an update of the available data to offer greater clarity regarding the risks of aspirin with respect to hemorrhagic stroke. In the secondary prevention of cardiovascular, cerebrovascular, and ischemic events, the evidence supports that the benefits of aspirin treatment significantly outweigh the risk of a major hemorrhage. When considering whether aspirin is appropriate, the absolute therapeutic cardiovascular benefits of aspirin must be balanced with the possible risks associated with its use, being hemorrhagic stroke. Regarding these clinical facts, normal, COX 1 ?/?, and COX 2 ?/? mice were treated with a wide range of doses of aspirin and studied by induced hemorrhagic time. The results outlined three major conclusions: high doses of aspirin induce hemorrhage, while low doses of aspirin do not. In the absence of COX 1, ultra low doses of aspirin produce an antihemorrhagic effect not observed with intermediate doses. The absence of COX 2 induced a hemorrhagic effect that needs further research, probably originated in compensatory phenomena. 1. Introduction Despite more than 100 years of use, acetyl salicylic acid (aspirin) has only been recognized for the prevention of myocardial infarction (MI) and ischemic stroke for the past 25 years. Over this period, based on its unique cost-effectiveness and widespread availability, the utilization of aspirin has expanded substantially for both primary and secondary prevention of cardiovascular events, providing significant insight into its safety and effectiveness. The decision as to which patients to treat must weigh the benefits of chronic aspirin therapy against the possible risks associated with its use, including the risk of intracerebral and subarachnoid hemorrhage, the most serious risks associated with the use of aspirin [1–7]. As the number of studies evaluating the long-term use of aspirin has expanded, it is now possible to evaluate the evidence in aggregate to more conclusively estimate the risk of hemorrhagic stroke, allowing a more informative benefit-risk assessment. The antithrombotic effectiveness of aspirin is related to its inhibition of the cyclooxygenase (COX) enzyme that metabolizes arachidonic acid to a variety of prostanoids, including thromboxane A2
Comparative effect of clopidogrel plus aspirin and aspirin monotherapy on hematological parameters using propensity score matching
Hayasaka M, Takahashi Y, Nishida Y, Yoshida Y, Hidaka S, Asai S
Vascular Health and Risk Management , 2013, DOI: http://dx.doi.org/10.2147/VHRM.S39351
Abstract: mparative effect of clopidogrel plus aspirin and aspirin monotherapy on hematological parameters using propensity score matching Original Research (603) Total Article Views Authors: Hayasaka M, Takahashi Y, Nishida Y, Yoshida Y, Hidaka S, Asai S Published Date February 2013 Volume 2013:9 Pages 65 - 70 DOI: http://dx.doi.org/10.2147/VHRM.S39351 Received: 18 October 2012 Accepted: 10 December 2012 Published: 18 February 2013 Masatoshi Hayasaka,1 Yasuo Takahashi,2 Yayoi Nishida,2 Yoshikazu Yoshida,1 Shinji Hidaka,3 Satoshi Asai4 1Department of Pharmacy, Nihon University Itabashi Hospital, Tokyo, 2Division of Genomic Epidemiology and Clinical Trials, Clinical Trials Research Center, Nihon University School of Medicine, Tokyo, 3Laboratory of Pharmaceutical Regulatory Science, Department of Pharmacy, School of Pharmacy, Nihon University, Chiba, 4Division of Pharmacology, Department of Biomedical Sciences, Nihon University School of Medicine, Tokyo, Japan Background: Clopidogrel and aspirin are antiplatelet agents that are recommended to reduce the risk of recurrent stroke and other cardiovascular events. Dual antiplatelet therapy with clopidogrel and aspirin has been shown to increase the risk of hemorrhage, but the effects of the drugs on laboratory parameters have not been well studied in real-world clinical settings. Therefore, we evaluated and compared the effects of combination therapy with clopidogrel plus aspirin and aspirin monotherapy on laboratory parameters. Methods: We used data from the Nihon University School of Medicine Clinical Data Warehouse obtained between November 2004 and May 2011 to identify cohorts of new users (n = 130) of clopidogrel (75 mg/day) plus aspirin (100 mg/day) and a propensity score matched sample of new users (n = 130) of aspirin alone (100 mg/day). We used a multivariate regression model to compare serum levels of creatinine, aspartate aminotransferase, and alanine aminotransferase, as well as hematological parameters including hemoglobin level, hematocrit, and white blood cell, red blood cell, and platelet counts up to 2 months after the start of administration of the study drugs. Results: There were no significant differences for any characteristics and baseline laboratory parameters between users of clopidogrel plus aspirin and users of aspirin alone. Reductions in white blood cell and red blood cell counts, hemoglobin levels, and hematocrit in users of clopidogrel plus aspirin were significantly greater than those in users of aspirin alone. Conclusion: Our findings suggest that adverse hematological effects may be greater with combination clopidogrel plus aspirin therapy than with aspirin monotherapy.
Comparative effect of clopidogrel plus aspirin and aspirin monotherapy on hematological parameters using propensity score matching  [cached]
Hayasaka M,Takahashi Y,Nishida Y,Yoshida Y
Vascular Health and Risk Management , 2013,
Abstract: Masatoshi Hayasaka,1 Yasuo Takahashi,2 Yayoi Nishida,2 Yoshikazu Yoshida,1 Shinji Hidaka,3 Satoshi Asai41Department of Pharmacy, Nihon University Itabashi Hospital, Tokyo, 2Division of Genomic Epidemiology and Clinical Trials, Clinical Trials Research Center, Nihon University School of Medicine, Tokyo, 3Laboratory of Pharmaceutical Regulatory Science, Department of Pharmacy, School of Pharmacy, Nihon University, Chiba, 4Division of Pharmacology, Department of Biomedical Sciences, Nihon University School of Medicine, Tokyo, JapanBackground: Clopidogrel and aspirin are antiplatelet agents that are recommended to reduce the risk of recurrent stroke and other cardiovascular events. Dual antiplatelet therapy with clopidogrel and aspirin has been shown to increase the risk of hemorrhage, but the effects of the drugs on laboratory parameters have not been well studied in real-world clinical settings. Therefore, we evaluated and compared the effects of combination therapy with clopidogrel plus aspirin and aspirin monotherapy on laboratory parameters.Methods: We used data from the Nihon University School of Medicine Clinical Data Warehouse obtained between November 2004 and May 2011 to identify cohorts of new users (n = 130) of clopidogrel (75 mg/day) plus aspirin (100 mg/day) and a propensity score matched sample of new users (n = 130) of aspirin alone (100 mg/day). We used a multivariate regression model to compare serum levels of creatinine, aspartate aminotransferase, and alanine aminotransferase, as well as hematological parameters including hemoglobin level, hematocrit, and white blood cell, red blood cell, and platelet counts up to 2 months after the start of administration of the study drugs.Results: There were no significant differences for any characteristics and baseline laboratory parameters between users of clopidogrel plus aspirin and users of aspirin alone. Reductions in white blood cell and red blood cell counts, hemoglobin levels, and hematocrit in users of clopidogrel plus aspirin were significantly greater than those in users of aspirin alone.Conclusion: Our findings suggest that adverse hematological effects may be greater with combination clopidogrel plus aspirin therapy than with aspirin monotherapy.Keywords: clopidogrel, aspirin, laboratory parameter, antiplatelet therapy, propensity score matching
Comparative evaluation of treatment with low-dose aspirin plus dipyridamole versus aspirin only in patients with acute ischaemic stroke
Arnarsdottir Lola,Hjalmarsson Clara,Bokemark Lena,Andersson Bj?rn
BMC Neurology , 2012, DOI: 10.1186/1471-2377-12-67
Abstract: Background Previous studies have suggested that pre-stroke treatment with low-dose aspirin (A) could reduce the severity of acute ischaemic stroke, but less is known on the effect of pre-stroke treatment with a combination of aspirin and dipyridamole (A + D) and post-stroke effects of these drugs. The aim of the present study was to evaluate the effect of this drug combination on acute and long-term prognosis of ischaemic stroke. Methods Patients without atrial fibrillation admitted to the stroke unit with acute ischaemic stroke (n = 554) or TIA (n = 108) were studied during acute hospital care and up to 12 months after discharge from hospital. Results Prior to acute stroke 62 patients were treated with A + D while 247 patients were treated with A only. No beneficial effects of the combination A + D compared to A only were noted on stroke severity and/or acute in-hospital mortality. However, survival analysis by Cox-proportional hazard model demonstrated lower 12-months all-cause mortality in patients discharged with A + D (n = 275) compared with patients on A only (HR, 0.52; CI, 0.32-0.86; p = 0.011; n = 262) after adjusting for age, baseline NIHSS, previous stroke, previous myocardial infarction and type 2 diabetes. We also noted a tendency towards lower all-cause mortality at 3 months with use of A + D, but this was not statistically significant (p = 0.12). Conclusions Pre-stroke treatment with a combination of low-dose A + D does not reduce the severity of acute stroke, nor does it reduce the acute in-hospital mortality. However, treatment with A + D at discharge from hospital is seemingly associated with lower long-term mortality compared with A only, contrary to the results from previous randomised studies. However, our results must be interpreted with extreme caution considering the non-randomised study design.
Is there an ideal way to initiate antiplatelet therapy with aspirin? A crossover study on healthy volunteers evaluating different dosing schemes with whole blood aggregometry
Saskia H Meves, Horst Neubauer, Ursula Overbeck, Heinz G Endres
BMC Research Notes , 2011, DOI: 10.1186/1756-0500-4-106
Abstract: Using whole blood aggregometry, this study with a prospective, uncontrolled, open, crossover design examined 12 healthy volunteers treated with three different aspirin loading doses: intravenous 500 mg aspirin, oral 500 mg aspirin, and a course of 200 mg aspirin on two subsequent days followed by a five-day course of 100 mg aspirin. Aspirin low response was defined as change of impedance exceeding 0 Ω after stimulation with arachidonic acid.Sufficient antiplatelet effectiveness was gained within 30 seconds when intravenous 500 mg aspirin was used. The mean time until antiplatelet effect was 74 minutes for 500 mg aspirin taken orally and 662 minutes (11.2 hours) for the dose scheme with 200 mg aspirin with a high inter- and intraindividual variability in those two regimes. Platelet aggregation returned to the baseline range during the wash-out phase within 4 days.Our study reveals that the antiplatelet effect differs significantly between the three different aspirin starting dosages with a high inter- and intraindividual variability of antiplatelet response in our healthy volunteers. To ensure an early platelet inhibitory effect in acute stroke patients, it could be advantageous to initiate the therapy with an intravenous loading dose of 500 mg aspirin. However, clinical outcome studies must still define the best way to initiate antiplatelet treatment with aspirin.Initiating early antiplatelet therapy with aspirin (acetylsalicylic acid, ASA) is important in treating patients with acute ischemic stroke or transient ischemic attacks (TIAs) and has been proven to significantly decrease the overall risk of further strokes or death [1-3]. Based on the results of two large randomized trials with up to 40 000 patients, present guidelines recommend starting aspirin treatment within 48 hours after stroke onset with doses varying from 100 mg to 325 mg to reduce the risk of early stroke recurrence [1-6].Recommendations for the antiplatelet treatment of coronary or peripheral di
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