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It is unknown whether the addition of dipyridamole to aspirin as pretreatment for patients undergoing percutaneous transluminal coronary angioplasty (PTCA) decreases acute complications. In this study 232 patients were prospectively randomized to receive either aspirin 325 mg orally 3 times daily (group 1, n = 115) or aspirin 325 mg orally 3 times daily plus dipyridamole 75 mg orally 3 times daily (group 2, n = 117) before elective PTCA. All clinical, angiographic and PTCA-related variables were similar between groups. Angiographic success rate was 93% in both groups. Clinical success was achieved in 107 patients (92%) in group 1 and in 101 patients (88%) in group 2 (difference not significant). Q-wave myocardial infarction occurred in 2 patients (1.7%) in group 1 and 5 patients (4.3%) in group 2 (difference not significant). Emergency coronary artery bypass grafting was required in 3 patients (2.6%) in group 1 and 7 patients (6.1%) in group 2 (difference not significant). There was 1 in-hospital death (in group 2). In this study, the addition of dipyridamole to aspirin as pretreatment of patients undergoing PTCA did not significantly reduce acute complications compared to aspirin alone.
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Two review authors independently selected trials for inclusion, assessed trial quality and extracted data. Data were analysed according to the intention-to-treat principle.
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The duration of intravenous heparin therapy required to maintain patency of the infarct-related artery after intravenous streptokinase is uncertain. Twenty-eight patients were prospectively treated with 1.5 million units of intravenous streptokinase within 4 hours of onset of chest pain. Intravenous heparin was begun after the streptokinase infusion was complete and was discontinued within 36 hours. Aspirin, 325 mg daily, and dipyridamole, 75 mg three times a day, was begun before the heparin was discontinued. Coronary angiography was performed both at 2 hours after completion of the streptokinase infusion and again at a mean of 8.7 (+/- 3.2) days after the initial catheterization. One patient died after treatment with streptokinase but before early angiography. In 21 of 27 patients (78%), Thrombolysis in Myocardial Infarction trial (TIMI) grade 2 or 3 perfusion in the infarct vessel was observed on initial angiography. Repeat angiograms were available in 17 of the 21 patients with initially patent vessels. Continued patency (TIMI grade 2 or 3) was found in 15 of the 17 patients (88%). Two of the four patients who did not undergo repeat angiography died, and the remaining two patients required coronary artery bypass grafting for unstable angina. Bleeding complications occurred in 6 of 27 patients (22%), with two (7%) requiring surgical evacuation of a groin hematoma. There were no instances of intracerebral bleeding and only two patients required transfusions. Thus, the combination of aspirin and dipyridamole following 36 hours of systemic heparinization after intravenous streptokinase infusion is associated with a reocclusion rate comparable to that which has been reported for more prolonged systemic anticoagulation with fewer hemorrhagic complications.
The latest guidelines do not make clear recommendations on the selection of antiplatelet therapies for long-term secondary prevention of stroke. We aimed to integrate the available evidence to create hierarchies of the comparative efficacy and safety of long-term antiplatelet therapies after ischemic stroke or transient ischemic attack.
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Extended release dipyridamole (DIP) is widely used in clinical practice as an Aggrenox formulation, which is proven to improve outcomes for secondary stroke prevention in patients after acute vascular events. However, presently established fluorometry techniques are not suitable for trace amount determinations, because of the variable background fluorescence. The authors sought to determine whether biological fluid pH is important for the serial measures of DIP levels in the animal experiments and in patients treated with Aggrenox after ischemic stroke. Post-stroke patient (n = 34) and mice (n = 25) samples were tested to determine DIP levels by established techniques with FluoroMax 3 spectrofluorometer. Both the absorption and emission spectra of DIP were affected by modifications in pH. Fluorescence of DIP was found to be maximal at a wavelength of 490 nm (excitation 420 nm) and the spectral pattern was independent of pH. The intensity of fluorescence, however, was drastically lower at low pH (at pH 2.6, fluorescence was 4% of intensity at pH 9.8). Background plasma fluorescence, however, was completely unaffected by changes in pH. Using these fluorometric characteristics, a regression model that facilitates the efficient and sensitive determination of DIP concentration in biological fluids was formulated. Exploiting pH-dependent characteristics of DIP versus serum fluorescence patterns permits a convenient mathematical model to determine DIP concentration. This relatively inexpensive and time-efficient procedure can quantify drug levels in human/animal plasma/serum, thereby directly determining the level of patient adherence to the prescribed drug regimen, be it in the context of clinical trials or compliance with the animal protocol.
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The precise role of antiplatelet therapy in secondary stroke prevention remains a matter of some debate. Although specific antiplatelet agents (notably aspirin, ticlopidine, dipyridamole, and clopidogrel) have been shown to be active in the prevention of secondary stroke, questions remain about the effective dose of these agents and their potential efficacy in combined therapeutic regimens. In addition, haematological and gastrointestinal side-effects of antiplatelet agents remain a significant clinical concern for patients and prescribing physicians. This review article examines research on both monotherapy and combination antiplatelet therapy for secondary stroke prevention, with an emphasis on lessons learned about dosage schedules, treatment protocols, and side-effect profiles.
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Oral anticoagulant therapy with warfarin commenced pre-operatively (n = 102) to prevent coronary artery vein graft occlusions was compared in terms of efficacy and safety with dipyridamole and aspirin (n = 130) in a randomized consecutive series of patients. Anticoagulant therapy was started at least 2 weeks before coronary artery bypass surgery (CABG) and antiplatelet therapy was started at least 3 days before CABG with dipyridamole followed by a combination of 250 mg aspirin once a day via a nasogastric tube 6 h after CABG. Overall, vein graft patency at 3 months after surgery did not differ significantly between the anticoagulant group (203/275, 74%) and dipyridamole-aspirin group (238/311, 77%), but the occlusion rate for grafts with endarterectomy was higher in the anticoagulant (46%) than in the dipyridamole and aspirin group (16%), (P less than 0.05). The rate of peri-operative complications including deaths, re-operation and myocardial infarction was higher in the anticoagulant than antiplatelet group (26.5% vs 13.8%, P less than 0.05). The occurrence of postoperative bleeding complications did not differ significantly between the groups. Thus, oral anticoagulant therapy commenced pre-operatively has no advantages over conventional antiplatelet therapy in patients who undergo CABG. Neither antithrombotic regimens proved to be satisfactory for preventing acute bypass vein graft occlusions in this patient population with advanced coronary artery disease.
ASA/ER-DP thus offers a cost-effective alternative to ASA monotherapy for the prevention of recurrent ischemic stroke.
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The Cochrane Stroke Group Trials Register was searched and other relevant Cochrane Groups were contacted to search their specialised registers (last search 29 April 2002). In addition the Cochrane Controlled Trials Register, MEDLINE and EMBASE were searched and Dutch manufacturers of dipyridamole were contacted to identify further published and unpublished studies.
Five hundred forty-six patients (12.0 %) were taking antithrombotic drugs (aspirin, 313; warfarin, 134; cilostazol, 57; clopidogrel, 59; ethylicosapentate, 40; prostaglandin preparations, 41; ticlopidine, 29; icosapentate, 24; dipyridamole, 4); 116 and 29 patients, respectively, were managed with a combination of 2 or 3 agents. Among 490 patients whose medical records were precisely documented, 40.6 % underwent EGD without cessation. Bleeding and thromboembolic complications were not observed. The most common pre-existing comorbidity was ischemic heart disease (27.9 %), followed by carotid or intracranial large artery atherosclerosis (20.5 %), cerebral infarction or transient ischemic attack (20.3 %), and atrial fibrillation (15.9 %). Patients with pre-existing comorbidity requiring anticoagulants frequently underwent EGD without cessation.
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After cardiac valve replacement patients were blindly randomized into two groups, both receiving aspirin (330 mg) and dipyridamole (75 mg) twice daily and the oral anticoagulant acenocoumarol (Sintrom). An international normalized ratio of 2.0 to 2.99 was assigned to group A and 3.0 to 4.5 to group B; both groups were subsequently analyzed for thromboembolic and hemorrhagic complications. Final evaluation included 51 and 48 patients, respectively. The follow-up was 626 months for group A (12.3 months/patient) and 486 months for group B (10.1 months/patient). The frequency of thromboembolism was equal in both groups: one transient ischemic attack in group A (a rate of 1.92/100 patient-years) and two transient ischemic attacks in group B (a rate of 4.94/100 patient-years). There was, however, a statistical difference in bleeding complications between the two groups (p less than 0.02). Two patients bled in group A, a rate of 3.9% (3.8/100 patient-years), which represents an incidence of one episode each 25.6 years of treatment; 10 patients bled in group B, a rate of 20.8% (24.7/100 patient-years) representing an incidence of one episode each 4 years of treatment. We conclude that an international normalized ratio of 2 to 3 is safer than a ratio of 3 to 4.5 and confers good protection from thromboembolism when oral anticoagulant therapy is used conjointly with platelet function-inhibiting drugs in patients with mechanical substitute heart valves.