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In primary prevention trials conducted in low-risk subjects, aspirin is associated with a small reduction in ischemic strokes in women. It also reduces the incidence of stroke in patients with nonvalvular atrial fibrillation (NVAF), but warfarin is more effective in patients with high blood pressure, or left ventricular dysfunction, especially those aged >75 years. According to secondary prevention trials in patients after noncardioembolic ischemic stroke or transient ischemic attacks, aspirin at any dose between 50 and 1,300 mg per day reduces the risk of new events, but doses >150 mg per day are associated with a worse gastrointestinal tolerance. Clopidogrel and a combination of aspirin plus extended-release dipyridamole are both slightly more effective than aspirin, but the combination of aspirin and clopidogrel does not reduce the risk of new vascular events and increases life-threatening bleedings. Aspirin cannot be recommended for secondary prevention in NVAF, except in the case of absolute contraindications to warfarin. The available data show that at the acute stage of ischemic stroke, aspirin is safe and slightly more effective than placebo or heparin, even in NVAF, but other antiplatelet agents have not been evaluated.
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This review addresses 2 fields: secondary prevention after cerebral ischaemia of cardiac origin (CICO) and that after cerebral ischaemia of arterial origin (CIAO). The major trial after CICO is the EAFT that showed the superiority of mild oral anticoagulation (INR 2-3) over aspirin and placebo. Despite several more recent trials with ximelagatran (e.g. SPORTIF and ACTIVE-W) the current standard remains mild oral anticoagulation. After CIAO several trials tried to improve the 13% relative risk reduction achieved with aspirin. Attempts with oral anticoagulation were disappointing: high INRs were not safe (SPIRIT), low INRs not effective (WARSS) and with a mild regimen (INR 2-3) the benefits for ischaemic events were cancelled by more major bleeding. Clopidogrel tended to be modestly more effective than aspirin after stroke (CAPRIE), but its combination with aspirin appeared not to be safe (MATCH, CHARISMA). Combination of aspirin with dipyridamole, however, was safe and more effective than aspirin alone (ESPS-2, ESPRIT). Recent American and European guidelines mention both the combination of aspirin and dipyridamole and clopidogrel monotherapy for secondary prevention after cerebral ischaemia of arterial origin. The recent PRoFESS trial found no differences in the efficacy of aspirin plus dipyridamole and clopidogrel, hence there is no need for major adaptation of the guidelines.
HF patients show an increase in inflammatory indices independently of underlying A therapy.
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The results strongly indicate the effectiveness and safety of combined warfarin plus antiplatelet treatment after St. Jude Medical valve replacement for mitral (plus aortic) valve disease.
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Our objective was to investigate the association between recurrent stroke risk and headache induced by extended-release dipyridamole (ER-DP) when administered alone or with low-dose aspirin (ASA+ER-DP).
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Despite recent advances in the acute treatment of stroke, prevention and risk factor modification remain the mainstays of management for patients with ischemic stroke and transient ischemic attack. The majority of noncardioembolic ischemic strokes are atherothrombotic, presumed to be associated with the activation and aggregation of platelets. Antiplatelet medications have been shown to be effective in the secondary prevention of stroke of presumed arterial origin, both as monotherapy and in combination. Among combination of antiplatelet agents, aspirin plus extended-release dipyridamole has demonstrated statistically significant additive benefit over monotherapy with each agent. Clopidogrel plus aspirin does not prevent recurrent ischemic stroke over each component individually, and the combination increases the risk of hemorrhagic side effects. This article reviews the most recent studies on antiplatelet medications, including the combination of aspirin and clopidogrel or extended-release dipyridamole, and discusses some of the controversies that still exist with the use of antiplatelet agents.
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Anticoagulants and antiplatelet agents are underutilized in the nursing home setting, perhaps because trials demonstrating treatment efficacy excluded people resembling those with long-term care needs. We sought to quantify the effect of antiplatelet and anticoagulant agents on risk of hospitalization for bleeding among an elderly nursing home population.
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The total efficiency of treatment group (65.71%) is better than that of control group (36%). Treatment group is obviously better than control group on decreasing hematuria and improving immune function.
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More and more patients receiving anticoagulant therapy or other drugs modifying the coagulation mechanism require dental or oral surgical treatment nowadays. The reason is that in Hungary the various forms of thrombosis are on the first place of morbidity and mortality lists. More than 50 per cent of all the mortality is due to thromboembolism. In view of all this it is not surprising that in the past years the indications, application and dosage of anticoagulant and platelet aggregation inhibitor drugs have changed. Decades-old principles have been modified. It is important for dentists and oral surgeons to know the risk of interventions in patients receiving anticoagulant or platelet inhibitory therapy.
Overall, only half of our elderly population received any pharmacological agent for secondary prevention of stroke. Interventions designed to improve the pharmacological management of recurrent stroke regardless of race are needed in the nursing home setting.
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Based on the results from these 2 large, randomized trials, ASA + dipyridamole was more effective than ASA monotherapy as first-line therapy for secondary stroke prevention in these patients with a history of minor stroke or TIA of noncardioembolic etiology.
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The second European Stroke Prevention Study investigated the prevention of stroke and/or death in 6602 patients with transient ischaemic attack or stroke with aspirin (25 mg b.d.), dipyridamole (400 mg b.d.), the combination of aspirin and dipyridamole or placebo. This post hoc analysis investigated cardiac events in patients with coronary heart disease or myocardial infarction (MI) at entry. Dipyridamole did not result in a higher number of cardiac events, e.g. angina pectoris, MI, or death from all causes. The combination of aspirin plus dipyridamole was superior to either drug alone in the prevention of stroke.
A virtually nationwide survey was performed among Hungarian neurologists involved in stroke care, who responded to a questionnaire concerning the use of antiplatelet agents and anticoagulation in acute ischemic stroke and for secondary prevention.
Dipyridamole (DP) is an antiplatelet agent that shows decreased oral bioavailability with increased gastric pH that occurs with commonly prescribed antacids. An extended-release (ER) formulation of DP that employs tartaric acid to improve bioavailability of DP in the presence of elevated gastric pH was developed as a combination antiplatelet product with immediate-release aspirin. This crossover-designed study examined the relative bioavailability of DP from the composite product compared to conventional DP tablets during reduced gastric acidity. Gastric pH was increased (pH > 4.0) in 20 healthy subjects with lansoprazole (30 mg/d for 5 days). Dipyridamole systemic exposure over 12 hours was compared after oral administration of a single composite ER capsule (200 mg DP + 25 mg aspirin) versus two 100-mg conventional DP tablets given 6 hours apart combined with 81 mg aspirin. DP relative bioavailability was reduced 53% with conventional tablets compared to the composite buffered ER capsule in reduced gastric acid conditions. Peak DP plasma concentrations were 57% lower with immediate-release tablets compared to the composite formulation with high stomach pH. Substituting generic DP plus low-dose aspirin may be less effective than the buffered DP composite product in patients with concomitant antacid therapies.
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The risk of end point events was greater in diabetic than in nondiabetic subjects. Total end point reduction in individuals receiving the combination of dipyridamole and acetylsalicylic acid was 39% in nondiabetic subjects and 23% in diabetic subjects in the explanatory analysis, and the reduction in the risk of stroke was 48% and 32%, respectively. However, a statistically significant reduction of risk was obtained only in nondiabetic subjects.
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In a double blind pilot study, we examined the effects of the stable prostacyclin derivate taprostene compared to a combination of aspirin and dipyridamole on platelet uptake and clinical outcome after peripheral percutaneous angioplasty. Taprostene was administered to 19 patients as a continuous intravenous infusion from 2 hours before until 8 (n = 6) or 24 (n = 6) hours after angioplasty; 7 control patients were given a combination of 330 mg aspirin and 75 mg dipyridamole. Uptake of 111-indium labelled platelets at the site of the PTA was measured 3 hours before and 4 and 24 hours after angioplasty. Clinical parameters were obtained one day before PTA, on the following day and 3 months after the procedure. There was a tendency for slightly higher platelet uptake ratios in the taprostene groups as compared to the control group especially in patients requiring technically difficult procedures. There were no differences between the 3 groups with regard to primary success or periinterventional complications. In the taprostene patients, 3 early reocclusions were found up to 72 hours after the procedure and 1 late reocclusion within 3 months. In the control group, no reocclusion was apparent in the observation time. No advantages were found when taprostene was administered during angioplasty as compared to conventional treatment with aspirine and dipyridamole.
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Sixty patients were recruited, 30 in each arm. The primary end point of change in embolic signal frequency did not differ between groups (P=0.36). In patients with embolic signals at baseline, there was no difference in reduction in embolic signal frequency: dipyridamole (75.5; SD 17.7%) versus clopidogrel (77.5; SD 20.5%; P=0.77). Baseline platelet aggregation was not different between regimens, but at 48 hours, adenosine 5'-diphosphate aggregation rate (but not collagen) was lower with clopidogrel (P<0.001).
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A prospective randomized trial was performed to determine if the administration of inhibitors of platelet function would improve the patency of coronary artery bypass grafts. Patients were operated on for intractable angina with angiographically demonstrable lesions. The left internal mammary artery (IMA) was used for bypass of lesions of the left anterior descending coronary artery (LAD). Saphenous vein grafts were used for the LAD if the IMA was inadequate and for all other vessels. Treated patients received 1,300 mg of aspirin and 100 mg of dipyridamole (Persantine) orally each day. Control patients received neither drug. Patients returned 3 to 6 months after operation for repeat angiography. Results were analyzed by chi-square. One hundred seventy-four patients entered the study from June, 1973, through December, 1975, and 113 were analyzed. In the control group, 66 patients had 27 IMA-LAD grafts and 93 saphenous vein grafts. In the treatment group, 47 patients underwent 18 IMA-LAD grafts and 75 saphenous vein grafts. Ninety-eight of the 120 grafts (82%) were patent in the control group, and 87 of 93 grafts (94%) were patent in the treatment group (x2 = 6.34, p less than 0.02). Of the 45 IMA-LAD grafts in both groups, only 1 was occluded, a patency of 98%. In the control group, 72 of 93 saphenous vein grafts (77%) were patent. In the treatment group, 69 of 75 (92%) were patent (x2 = 6.54, p less than 0.02). The results of the study show a 15% difference between the two groups in the early patency of saphenous vein grafts. We continue to use aspirin and dipyridamole to improve the patency of saphenous vein bypass grafts.
Little is known about the site and nature of bleeding lesions related to low-dose aspirin and other antithrombotic agents.
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DP is often associated with subsiding headache, however, with only few patients stopping medication due to headache. Being a younger female with a TIA seems to increase the risk of getting headache when having DP medication. Careful and adequate information about the possibly occurring headache should be given to patients prescribed a DP medication in order to increase compliance and optimize the pharmacological secondary stroke prevention.
After adjustment, use of warfarin (odds ratio [OR], 1.26; 95% CI, 1.11 to 1.43) and combination therapy (OR, 1.34; 95% CI, 0.99 to 1.82) were associated with an increased risk of hospitalization for a bleed compared with nonusers. The odds of aspirin use was greater among cases than controls (OR, 1.07; 95% CI, 0.96 to 1.18) after adjustment.
In the Persantine-Aspirin Reinfarction Study, Part II (PARIS II), 3,128 persons who had recovered from myocardial infarction, suffered from 4 weeks to 4 months previously, were randomized into two groups: dipyridamole (Persantine) plus aspirin (n = 1,563) and placebo (n = 1,565). The average length of follow-up was 23.4 months. Prespecified primary end points were coronary incidence (definite nonfatal myocardial infarction plus death due to recent or acute cardiac event), coronary mortality (death due to recent or acute cardiac event) and total mortality, each at 1 year of patient follow-up and at the end of the study. Coronary incidence in the Persantine plus aspirin group was significantly lower than in the placebo group, both at 1 year (30% reduction) and at the end of the study (24% reduction). The statistically significant differences in coronary incidence, at 1 year and at the end of the study, in favor of the combination treatment remained after adjustment for multiple baseline variables and adjustment for multiple testing (three end points for two time periods). Although there were reductions for other end points, these differences were not statistically significant. Coronary mortality was 20% lower in the Persantine plus aspirin group compared with the placebo group at 1 year, and 6% lower overall. Total mortality in the treated group compared with the placebo group was 11% lower at 1 year and 3% lower overall. The reduced rates of coronary incidence largely reflected lower rates of definite nonfatal myocardial infarction in the Persantine plus aspirin group. Several subgroups were defined a priori and at the end of the study. The beneficial effect of Persantine plus aspirin compared with placebo for coronary incidence tended to be greater for the following groups of patients: those who had a non-Q wave infarct; those who were not taking digitalis; those who were receiving beta-receptor blocking drugs at baseline; those who were in New York Heart Association functional class I; those who had had only one myocardial infarction; or those who were enrolled in the study early, that is within 85 days of the qualifying myocardial infarction.
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To develop evidence-based clinical practice guidelines for interventional techniques in the diagnosis and treatment of chronic spinal pain.
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Stroke is a devastating complication in patients with prosthetic valves, but characterization of its late occurrence from a large cohort is lacking.
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In patients with TIA or stroke of arterial origin various antiplatelet agents, or combinations of these, have been found to be effective to reduce the risk of new vascular complications. International guidelines currently recommend three treatment strategies with antiplatelet agents after TIA or stroke: acetylsalicylic acid in combination with dipyridamole, clopidogrel monotherapy, or alternatively acetylsalicylic acid monotherapy. In the Netherlands, current standard antiplatelet therapy after a TIA or stroke is a combination of acetylsalicylic acid and dipyridamole. Clopidogrel monotherapy is probably equally as effective as the combination of acetylsalicylic acid and dipyridamole. Clopidogrel monotherapy is easier to use, has fewer side effects and has recently become cheaper than the combination of acetylsalicylic acid and dipyridamole. For secondary prevention in the Netherlands we advise following the international guidelines on thromboprophylaxis after TIA or stroke. Clopidogrel could be considered as an alternative treatment to the combination of acetylsalicylic acid and dipyridamole.
Antiplatelet therapy with dipyridamole, 100 mg q.i.d., starting 2 days before surgery, followed by aspirin, 325 mg t.i.d. plus dipyridamole, 75 mg t.i.d., 7 hours after surgery was assessed in the prevention of saphenous vein bypass graft occlusion. Early (less than or equal to 1 month) and late (1 year) occlusions were reduced both on a per patient and a per distal anastomosis basis. Bleeding complications were not increased. Graft occlusion in high-risk situations (low-flow grafts and endarterectomy) was reduced, but not eliminated, by this antiplatelet regimen. The authors recommend this combination of dipyridamole before surgery, adding aspirin after surgery, to prevent coronary artery bypass graft occlusion.
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Nine cases of nephrotic children associated with focal segmental glomerulosclerosis who had failed to respond to prednisone and cyclophosphamide therapy and showed sign of progressive deterioration of renal function, were subjected to the therapeutic combinations of antiplatelet agents + prednisone +/- anticoagulant agents. Initially, all were hypertensive, 77.8% had creatinine clearance of less than 60 ml/min/1.73 m2 and associated infections were documented in eight of nine cases. With therapy, improvement in clinical status as well as renal function and platelet kinetics were substantiated in all of the studied cases. Thus, this mode of therapy appears to be beneficial in these nephrotic children in whom associated infection is a potentially threatening factor.