SECONDARY PREVENTION OF MYOCARDIAL INFARCTION
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Sulfinpyrazone
Dipyridamole
Secondary Prevention
Abstract One hundred and one subjects were randomised to receive either aspirin 100 mg or aspirin 100 mg + dipyridamole 300 mg daily before undergoing coronary bypass surgery. The drugs were commenced at least 36 hours before operation and patients were followed for one year. There were three perioperative deaths and 37 withdrawals, of which 14 were drug related (aspirin four, aspirin + dipyridamole ten). Cineangiocardiograms at nine weeks and one year showed vein graft patency rates of 93% and 87% for subjects treated with aspirin alone; and 90% and 89% in those who received aspirin + dipyridamole. During the follow‐up period 14% of 232 coronary lesions in the aspirin treated group advanced by more than two grades compared with 15% of 315 lesions in the aspirin + dipyridamole group. The study did not establish superiority of one regimen over another in terms of graft patency or progress of lesions in native vessels. However, low dose aspirin was better tolerated than combination therapy. (Aust NZ J Med 1992; 22: 665ndash;670.)
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Dipyridamole
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The recognition that stroke and other ischemic events are manifestations of chronic progressive inflammation has had a great impact on the development of prevention strategies. The most recent American Heart Association guidelines recommend combination aspirin and extended-release dipyridamole over aspirin alone for patients with prior ischemic stroke or transient ischemic attack. Although aspirin and extended-release dipyridamole have long been recognized for their antiplatelet activities, there is now evidence that these drugs also have complementary antiinflammatory properties that contribute to improved outcomes when used to prevent secondary stroke. In the Second European Stroke Prevention Study (ESPS-2), the addition of extended-release dipyridamole to low-dose aspirin significantly reduced the risk of recurrent ischemic stroke without significantly increasing bleeding. Also, in the recent European/Australasian Stroke Prevention in Reversible Ischaemia Trial (ESPRIT), a combination of aspirin and extended-release dipyridamole was superior to aspirin alone for reducing the occurrence of the primary combined end point of vascular death, nonfatal stroke, nonfatal myocardial infarction, and major bleeding complications. The added benefit without worsening bleeding may be attributable, in part, to the antiinflammatory actions of this combination therapy.
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Publication of the results of the second European Stroke Prevention Study(ESPS-2) provided the incentive for an update of the meta-analyses of aspirin and dipyridamole in the secondary prevention of stroke. After review of published randomized trials of prolonged treatment with aspirin, dipyridamole, or their combination in patients with a history of stroke or transient ischemic attack (TIA), data on the occurrence of stroke, myocardial infarction, and vascular death were used to calculate overall relative risk reductions. The relative risk reduction for aspirin versus placebo was 13%. The same relative risk reduction was found in separate meta-analyses of trials with high (1,000-1,500 mg), medium (250-500 mg), and low (50-100 mg) doses of aspirin. Trials in which different doses were compared showed no difference in the occurrence of vascular events. The addition of dipyridamole to low-dose aspirin further reduced the risk for vascular events by 15%. We conclude from current trials that low-dose aspirin alone reduced the risk of vascular events in patients with prior stroke or TIA by 13%. There is no evidence of a dose-effect relationship. An additional reduction of the risk by 15% can be obtained by adding dipyridamole to aspirin. The overall evidence for the relative effects of the combination of dipyridamole and aspirin versus aspirin alone or placebo is highly consistent. The clinical evidence now favors the two agents in combination over aspirin alone.
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Aspirin, aspirin plus dipyridamole, or clopidogrel often is used to prevent recurrent stroke. In the double-blind randomized PRoFESS trial, more than 20,000 clinically stable patients (age, 50) with recent ischemic strokes received either a fixed combination of aspirin (25 mg) plus extended-release dipyridamole (200 mg) twice daily or clopidogrel (75 mg) once daily. The study was sponsored by the maker of the aspirin/dipyridamole …
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Dipyridamole
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The second European Stroke Prevention Study (ESPS-2) recently reported a substantial benefit of dipyridamole combined with aspirin over aspirin alone in the prevention of stroke. This appears to be at odds with previous studies suggesting that dipyridamole adds nothing to aspirin alone.To review and compare the results of ESPS-2 and previous studies of dipyridamole plus aspirin and aggregate them in a meta-analysis.We combined the detailed data provided by the Antiplatelet Trialists' Collaboration on the previous studies of dipyridamole plus aspirin with the results from ESPS-2. The data on the previous trials were listed in the appendix of the 1994 publication of the Antiplatelet Trialists' Collaboration.The results of our meta-analysis demonstrate that for the outcome of nonfatal stroke, ESPS-2 overwhelms previous data, which, even in the aggregate, did not include enough patients or outcome events to exclude efficacy for the combination of dipyridamole and aspirin. Differences between ESPS-2 and previous studies, which may have contributed to different results, include the doses and preparations of aspirin and dipyridamole.The ESPS-2 showed that dipyridamole alone prevents stroke. More importantly, it showed a substantial benefit for dipyridamole combined with aspirin over aspirin alone. When the ESPS-2 data are aggregated with the 14 previous trials of dipyridamole combined with aspirin over aspirin alone, the combination reduces the risk of stroke by 23% over aspirin alone. Nevertheless, important questions remain unanswered. We conclude that another randomized clinical trial showing a significant benefit of the combination of dipyridamole plus aspirin over aspirin alone may be needed before the addition of dipyridamole to aspirin is widely accepted for prevention of stroke.
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