ozagrel and Stroke

Many of these therapies have been compared against placebos, but have not been directly compared against each other. To evaluate the efficacy and safety of several commonly used drugs for AIS directly or indirectly.. A systematic literature review was performed to identify randomized controlled trials (RCTs) published prior to April 2013 for AIS therapies. The primary outcome measures were the National Institutes of Health Stroke Scale (NIHSS) scores and the clinical effective rate. A fixed-effects meta-analysis and meta-regression are performed; lastly, performed a mixed treatment comparison was performed through the Bayesian methods.. Outcome of efficacy of therapies for acute ischemic stroke are as followed: All of the therapies mentioned above yielded results a more effective result than placebo, Sodium ozagrel (RR 3.86, 95%CI 3.18-4.61); Sodium ozagrel + edaravone (RR 9.60, 95%CI 7.04-13.06); Edaravone (RR 4.07, 95%CI 3.30-5.01); Edaravone + Kininogenase (RR 15.33, 95%CI 10.03-23.05). The significant difference in efficacy between edaravone monotherapy and Sodium ozagrel + edaravone was evident (RR 0.43, 95%CI 0.08-0.61) and was also significant between efficacy of edaravone + Kininogenase and Sodium ozagrel (RR 4.00, 95%CI 2.47-6.24). The differences between the risk and benefit were not significant when comparing Sodium ozagrel and edaravone or edaravone + Kininogenase and Sodium ozagrel + Edaravone for AIS. Outcome of the defect of neurological function: Placebo served a significant difference in treating the defects of neurological function compared with Sodium ozagrel (WMD = -3.11, 95%CI -4.43 to -1.79), Sodium ozagrel + edaravone (WMD = -6.25, 95%CI -7.96 to -4.54) and Edaravone + Kininogenase (WMD =  -3.47, 95%CI -5.73 to -1.21).. It provides that the efficacy of edaravone monotherapy in treatment was not more effective than Sodium ozagrel + edaravone.The efficacy of edaravone + Kininogenase monotherapy in treatment was more effective than Sodium ozagrel. Edaravone + Kininogenase and Sodium ozagrel + Edaravone appeared the most effective treatments. And Sodium ozagrel, Sodium ozagrel + edaravone, Edaravone + Kininogenase can improve the nerve dysfunction.

Topics: Aged; Antipyrine; Bayes Theorem; China; Coagulants; Drug Therapy, Combination; Edaravone; Fibrinolytic Agents; Free Radical Scavengers; Humans; Kallikreins; Methacrylates; Randomized Controlled Trials as Topic; Stroke; Treatment Outcome

In patients with acute ischemic stroke (AIS), platelets are activated in the acute phase, releasing neurotoxic, and thrombogenic eicosanoids, which may reduce the brain blood flow and cause brain damage. Sodium ozagrel (ozagrel), a thromboxane A2 synthase inhibitor, is one of the most studied drugs which may reduce the risk of neurological impairment and reduce the volume of brain damage. We systematically reviewed all published randomized controlled trials (RCTs) comparing ozagrel with control among patients with AIS.. We searched seven databases, using the Cochrane Stroke Group search strategy and the terms of ozagrel and stroke. Two independent investigators evaluated trial quality using the Cochrane Collaboration's risk of bias tool and extracted the data from each study. Pooled analyses for the outcomes of combined death or disability and improvement of neurological impairment were calculated.. The effect of ozagrel on the reduction of death for AIS at the end of follow-up was relative risk (RR) = 0·67 (95% CI: 0·11 to 4·04, P = 0·67). The effect evaluated by Modified Edinburgh-Scandinavian Stroke Scale (MESSS) at the end of treatment was mean difference (MD) = -4·17 (95% CI, -4·95 to -3·40; P<0·00001). The most severe adverse events of ozagrel were digestive hemorrhage and hemorrhagic stroke; however, there was no significant difference between the two groups. The subgroup analysis of different dose showed that 80 and 160 mg ozagrel per day might both increase the improvement of the neurological impairment.. During scheduled treatment, ozagrel is effective for the improvement of neurological impairment for AIS patients. However, the evidence of ozagrel to reduce the long-term death or disability is limited and quality of these trials is insufficent hence, large-sample and high quality RCTs are warrented to confirm the efficacy of ozagrel for acute ischemic stroke.

Topics: Brain Ischemia; Dose-Response Relationship, Drug; Fibrinolytic Agents; Humans; Methacrylates; Randomized Controlled Trials as Topic; Stroke; Treatment Outcome

The management for acute stroke has been changed greatly in Japan. Because use of intravenous administration of tissue plasminogen activator (IV-t-PA) for acute brain infarction within 3 hours of onset has been approved by Japanese government from October, 2005. Now, if acute stroke patient arrivals at hospital within 3 hours of onset, we consider that such patients should be treated with t-PA therapy. The accurate diagnosis should be made by systematic evaluation using CT/MRI, neurosonology including transcranial Doppler, carotid echography, and echocardiography (TEE and TTE), SPECT, and angiography. In particular, it is important to assess the arteries from heart and brain. The grad A for treatment of acute stroke is recommended as IV-t-PA therapy, aspirin administration within 48 hours of stroke onset, and the management in stroke unit. In particular, stroke unit can improve functional outcome and to reduce the length of hospital stay. The evidence directing therapy for acute stroke is changing rapidly.

Topics: Activities of Daily Living; Aspirin; Diagnostic Imaging; Humans; Length of Stay; Methacrylates; Neurologic Examination; Patient Care Planning; Patient Care Team; Platelet Aggregation Inhibitors; Quality of Life; Stroke; Time Factors; Tissue Plasminogen Activator

Topics: Abciximab; Antibodies, Monoclonal; Aspirin; Fibrinolytic Agents; Humans; Immunoglobulin Fab Fragments; Methacrylates; Platelet Aggregation Inhibitors; Stroke

Topics: Anticoagulants; Antipyrine; Arginine; Aspirin; Brain Edema; Edaravone; Fibrinolytic Agents; Free Radical Scavengers; Glycerol; Humans; Hyperlipidemias; Hypertension; Japan; Methacrylates; Pipecolic Acids; Platelet Aggregation Inhibitors; Practice Guidelines as Topic; Risk Factors; Stroke; Sulfonamides; Thrombolytic Therapy; Time Factors; Warfarin

Topics: Animals; Arginine; Drug Therapy, Combination; Heparin; Humans; Methacrylates; Pipecolic Acids; Recombinant Proteins; Streptokinase; Stroke; Sulfonamides; Time Factors; Tissue Plasminogen Activator

Cilostazol, an inhibitor of phosphodiesterase 3, has various pleiotropic effects besides its antiplatelet activity. This study examined the efficacy of cilostazol for the treatment of acute perforating artery infarction.. In this prospective, randomized, open-label, blinded-end point trial, 100 patients with cerebral infarction in the territory of the lenticulostriate arteries were enrolled within 48 h of onset. Patients were randomly treated with both cilostazol and ozagrel for 14 days (n = 50, cilostazol group) or ozagrel alone for 14 days (n = 50, control group). The primary end point was the proportion of favorable outcomes 30 days after randomization as defined by a modified Rankin Scale (mRS) score of 0-2. Secondary end points included the incidence of neurological deterioration (an increase of ≥ 2 on the National Institutes of Health Stroke Scale within 7 days).. Favorable outcomes (mRS scores 0-2) were similar in both groups (81.3 and 82.0% in the cilostazol and control groups, respectively). The incidence of neurological deterioration was lower in the cilostazol group than the control group (12.5 and 16.0%, respectively) with a 21.9% relative risk reduction, although the difference was not statistically significant.. Cilostazol did not prevent the neurological deterioration of perforating artery infarction.

Topics: Aged; Aged, 80 and over; Brain Ischemia; Cilostazol; Double-Blind Method; Drug Therapy, Combination; Female; Fibrinolytic Agents; Humans; Male; Methacrylates; Middle Aged; Stroke; Tetrazoles; Time Factors; Treatment Outcome

Measurements of platelet reactivity and assessment of the efficacy of antiplatelet drugs are widely recognized as pre-requisite for the diagnosis and treatment of stroke patients. A recently established shear-induced platelet reactivity test using non-anticoagulated blood (the Global Thrombosis Test) has facilitated measurements of physiologically relevant platelet function and thrombolytic activity. 195 healthy volunteers, not taking antiplatelet drugs or anticoagulants, and 185 patients with acute cerebrovascular diseases were enrolled. The effect of antiplatelet drugs on platelet function and thrombolytic activity was assessed using the Global Thrombosis Test after 14 days of medication. The occlusion time (OT), an index of platelet reactivity, in healthy controls was 284.9 ± 92.2 s. The lysis time (LT), an index of thrombolytic activity, in healthy controls was 2,231 ± 1,223 s. Both times had no significant difference between males and females. The OT of all stroke patients was 210.3 ± 140.8 s and was shorter than that of the healthy controls (284.9 ± 92.2, p < 0.0001). The LT of all stroke patients was 3,159 ± 1,549 s and was longer than that of the controls (2,231 ± 1,223, p < 0.0001). Medication significantly prolonged the OT from 184.5 ± 150.6 s (before) to 295.3 ± 208.1 s (after) in all patients, indicating a reversal of the hyper-platelet reactivity. In addition, medication shortened the LT from 3,924 ± 1,718 s (before) to 3,107 ± 1,794 s (after) in all patients. A prothrombotic state exists in stroke patients due to enhanced platelet function and suppressed thrombolytic activity. Medication improved these physiological parameters of haemostasis.

Topics: Adult; Aged; Anticoagulants; Aspirin; Blood Coagulation; Blood Platelets; Cerebral Infarction; Female; Fibrinolytic Agents; Humans; Male; Methacrylates; Middle Aged; Platelet Aggregation; Platelet Aggregation Inhibitors; Platelet Function Tests; Stroke; Young Adult

Edaravone, a free radical scavenger approved by the Japanese Ministry of Health, Labor and Welfare in 2001 for treating acute ischemic stroke, was recommended by the Japanese Guidelines for the Management of Stroke 2004. While edaravone also has a neuroprotective profile, there is no other recognized drug that can verify its effect in clinical trials despite the need for neuroprotection. We performed a postmarketing clinical trial to provide further reliable evidence concerning edaravone in patients with acute ischemic stroke.. We conducted a multicenter randomized parallel-group open-label trial of edaravone intravenously and a control drug, sodium ozagrel (ozagrel), a thromboxane A(2) synthase inhibitor, intravenously in acute noncardioembolic ischemic stroke. The primary endpoint was the modified Rankin Scale at 3 months after treatment initiation.. In total, 401 patients were initially enrolled. The rate of 'grade 0-1' on the modified Rankin Scale, as assessed at 3 months, was 57.1 and 50.3% in the edaravone and ozagrel groups, respectively. The intergroup difference was 6.8% (95% confidence interval = -3.1 to 16.7), indicating noninferiority of edaravone to ozagrel, since the lower limit of the confidence interval did not exceed -11.4%. There were no particular concerns over the safety of edaravone.. This trial verified that edaravone was not inferior to ozagrel. Edaravone was at least as effective as ozagrel for the treatment of acute noncardioembolic ischemic stroke.

Topics: Aged; Aged, 80 and over; Antipyrine; Edaravone; Female; Free Radical Scavengers; Humans; Japan; Male; Methacrylates; Middle Aged; Platelet Aggregation Inhibitors; Stroke; Treatment Outcome

Argatroban is a thrombin inhibitor agent for acute noncardioembolic ischemic stroke in Japan. We studied the prognosis in patients with acute stroke treated by argatroban in comparison with the control group with ozagrel in our hospital.. A total of 513 patients with acute noncardioembolic ischemic stroke were enrolled retrospectively from our hospital database. Of all patients with stroke, 353 were administered with argatroban. The other 160 control patients were administered with ozagrel. The patients were examined as to their stroke types, the neurological severity according to the National Institutes of Health Stroke Scale (NIHSS), and clinical outcomes on discharge were determined according to the modified Rankin Scale (mRS).. A total of 353 patients with acute noncardioembolic stroke, including 138 with lacunar infarction (LIs) and 215 with atherothrombotic infarction (ATI) showed functional recovery by argatroban, but the effectiveness of argatroban was not superior to ozagrel therapy defined by the control group. A total of 255 patients with ATI who were treated with both argatroban and ozagrel showed improvement by 1 point. We could not find any significant difference between argatroban and ozagrel in the 2 stroke subtypes, LI and ATI. We also found that combination therapy of argatroban and edaravone was not superior to argatroban monotherapy in clinical outcome.. Argatroban therapy was not superior to control with ozagrel therapy in acute noncardioembolic ischemic stroke, including LI and ATI, regardless of the use of edaravone.

Topics: Aged; Aged, 80 and over; Antithrombins; Arginine; Brain Ischemia; Female; Fibrinolytic Agents; Humans; Male; Methacrylates; Middle Aged; Pipecolic Acids; Prognosis; Retrospective Studies; Severity of Illness Index; Stroke; Sulfonamides

Ozagrel sodium (ozagrel), a thromboxane A2 synthesis inhibitor, is used for ischemic stroke patients in several countries, despite a lack of strict evidence of its benefits. We investigated whether ozagrel was beneficial for patients with atherothrombotic stroke or lacunar infarction.. This was a retrospective observational study using the Diagnosis Procedure Combination database in Japan. We identified patients with atherothrombotic stroke or lacunar infarction who were admitted to 781 hospitals from July 1, 2010 to March 31, 2012. Propensity score-matched analyses were performed separately for patients with atherothrombotic stroke and those with lacunar infarction, which balanced differences in baseline characteristics between patients who received ozagrel (ozagrel group) and those who did not (control group) in each stroke subtype. The modified Rankin Scale scores at discharge and occurrence of hemorrhagic complications after admission were compared between the ozagrel and control groups.. After the propensity score matching, 2726 pairs of patients with atherothrombotic stroke and 1612 pairs of patients with lacunar infarction were analyzed. Ordinal logistic regression analyses showed that ozagrel use was not significantly associated with modified Rankin Scale score at discharge in patients with atherothrombotic stroke (odds ratio: .99; 95% confidence interval: .88-1.11) or in those with lacunar infarction (odds ratio: 1.00; 95% confidence interval: .87-1.16). The occurrence of hemorrhagic complications did not differ significantly between the ozagrel and control groups.. The present study suggested that ozagrel was safe to use but did not improve functional outcomes in patients with atherothrombotic or lacunar infarction.

Topics: Adult; Aged; Aged, 80 and over; Brain Ischemia; Chi-Square Distribution; Disability Evaluation; Enzyme Inhibitors; Female; Hemorrhage; Humans; Logistic Models; Male; Matched-Pair Analysis; Methacrylates; Middle Aged; Patient Discharge; Propensity Score; Recovery of Function; Retrospective Studies; Risk Factors; Stroke; Stroke, Lacunar; Thromboxane-A Synthase; Treatment Outcome

We investigated the neuroprotective properties of single doses of minocycline and ozagrel when administered prior to stroke. Male Sprague-Dawley rats were assigned randomly to one of the following groups: (1) control (Con) group (n=10), (2) minocycline (Mino) group (n=10), (3) sodium ozagrel (SO) group (n=10). Rats were treated with a single dose of minocycline or ozagrel at 30min before stroke. A middle cerebral artery occlusion (MCAO) was made at 30min after drug administration and reperfusion was done. The rats were subjected to a neurobehavioral test at days 1, 3 and 7 after MCAO. The cerebral ischemic volume was quantified by MetaMorph imaging software after TTC staining. The neuronal cell survival and astrocytes expansion were assessed by the NeuN and GFAP immunohistofluorescence staining. Apoptosis was detected by the TUNEL assay. We statistically analyzed and compared the results with each other. Mino and SO groups had neuroprotective effect and showed a better behavioral performance of adhesive removal and treadmill test at 7 days after stroke. Mino and SO groups also showed a smaller infarct volume than control group at 7 days after stroke. Immunohistofluorescence staining showed a higher number of NeuN positive cells, lower activated astrocytes in GFAP and a lower apoptosis in TUNEL staining. This study showed that single doses of minocycline and ozagrel prior to stroke had neuroprotective effects. These agents will be useful not only in post-stroke therapy but also in stroke prevention in several cerebrovascular procedures like carotid endarterectomy, bypass procedure, endovascular angioplasty, thromboembolectomy or thrombolysis.

Topics: Animals; Apoptosis; Astrocytes; Brain; Cell Survival; Disease Models, Animal; Fibrinolytic Agents; Infarction, Middle Cerebral Artery; Ischemic Attack, Transient; Male; Methacrylates; Minocycline; Neurons; Neuroprotective Agents; Neuropsychological Tests; Random Allocation; Rats, Sprague-Dawley; Stroke; Treatment Outcome

A novel free radical scavenger, edaravone, has been demonstrated to exert a neuroprotective effect and improve outcomes in acute ischemic stroke, but there have been few clinical studies. Therefore, we investigated retrospectively whether the administration of edaravone at the acute stage of ischemic stroke can improve outcomes of the disease at the time of discharge. Between January 1998 and December 2011, 625 consecutive patients (331 males and 294 females: mean age 77.0 years, range 36-101 years) with acute ischemic stroke who were admitted to our institution within 48 hours after stroke onset were enrolled. Subtypes of strokes were lacunar infarction (LI) in 188 (30.0%), atherothrombotic infarction (ATCI) in 268 (42.0%), and cardioembolic infarction (CEI) in 169 (27.0%). Of the 625 patients, 237 (37.0%) received both edaravone and conventional treatment, while the other 388 (62.0%) patients underwent conventional treatment only. As a conventional treatment, 422 (67.0%) of 625 patients were treated with ozagrel sodium, and 37 patients received argatroban. The overall outcomes at discharge were favorable (modified Rankin Scale score 0-2) in 296 (47.4%) and death occurred (mRS score 6) in 86 (13.8%). In a univariate analysis, the administration of edaravone did not have a significant effect on total death from all types of cerebral infarction. However, treatment with edaravone showed a favorable tendency (p=0.099) compared to conventional treatment after adjustments for age and gender. Further investigation is required before a definite conclusion can be made.

Topics: Adult; Aged; Aged, 80 and over; Antipyrine; Arginine; Edaravone; Female; Free Radical Scavengers; Humans; Ischemia; Male; Methacrylates; Middle Aged; Pipecolic Acids; Retrospective Studies; Risk Factors; Stroke; Sulfonamides; Young Adult