Aspirin myocardial infarction secondary

The AHA/ASA guidelines recommend that antiplatelet therapy as the cornerstone of antithrombotic therapy for the secondary prevention of ischemic stroke and should be used in noncardioembolic strokes. Aspirin, dopidogrel, and extended-release dipyridamole plus aspirin are all considered first-line antiplatelet agents (see Table 13-1). The combination of aspirin and clopido-grel can only be recommended in patients with ischemic stroke and a recent history of myocardial infarction or coronary stent placement and then only with ultra-low-dose aspirin to minimize bleeding risk. 

Overview analyses have shown that low-dose aspirin reduces the secondary incidence of heart attack and stroke by about 25%. However, it elevates the low risk of serious gastrointestinal bleeding about twofold over placebo. Low-dose aspirin also reduces the incidence of first myocardial infarction. However, in this case, the benefit versus risk of gastrointestinal bleeding is less clear. The effects of aspirin on platelet function are discussed in greater detail in Chapter 34. 

The FDA has approved the use of 325 mg/d for primary prophylaxis of myocardial infarction but urges caution in this use of aspirin by the general population except when prescribed as an adjunct to risk factor management by smoking cessation and lowering of blood cholesterol and blood pressure. Meta-analysis of many published trials of aspirin and other antiplatelet agents confirms the value of this intervention in the secondary prevention of vascular events among patients with a history of vascular events. 

In view of the perceived benefit of aspirin in the secondary prevention of stroke and myocardial infarction, two large trials involving physicians as subjects were initiated to study the effect of aspirin in the primary prevention of arterial thrombosis. In the American study, 22,000 volunteers (age 40 to 84 years) were randomly assigned to take 325 mg of aspirin every other day or placebo. The trial was halted early, after a mean follow-up of 5 years, when a 45% reduction in the incidence of myocardial infarction and a 72% reduction in the incidence of fatal myocardial infarction were noted with aspirin treatment. However, total mortality was reduced only 4% in the aspirin group, a difference that was not statistically significant, and there was a trend for a greater risk of hemorrhagic stroke with aspirin. Thus, the prophylactic use of aspirin in an apparently healthy population is not recommended at this time, unless there are risk factors for cardiovascular disease. 

In the case of aspirin, there are numerous reports of beneficial effects of low-dose aspirin in the secondary prophylaxis of cardiovascular disease (myocardial infarction and stroke). Aspirin clearly reduces the risk of myocardial infarction and stroke among patients who already have manifestations of cardiovascular disease. 

The antiplatelet/antithrombotic activity of dipyridamole has been demonstrated in laboratory and in animal models, and has been shown to inhibit platelet aggregation and vessel-wall thrombogenesis [9-11]. Dipyridamole has been given either alone or with aspirin in the management of myocardial infarction and stroke. For the secondary prevention of stroke or transient ischemic attack, the drug may be given as a modified-release preparation in a dose of 200 mg twice daily. Dipyridamole administered intravenously results in a marked coronary vasodilation and is used in stress testing in patients with ischemic heart disease [5]. 

Patients in atrial fibrillation who have a TIA or stroke without other clear etiology should be given anticoagulation therapy if there are no contraindications (European Atrial Fibrillation Trial Study Group 1993, 1995). Recent studies have shown that warfarin is as safe as aspirin in elderly patients with atrial fibrillation (Rash et al. 2007 Mant et al. 2007). Patients with presumed cardioembolic TIA or stroke secondary to other causes should certainly receive antithrombotic therapy. Also they may benefit from anticoagulation in certain circumstances, such as intracardiac mural thrombosis after myocardial infarction, although there have been no randomized trials in situations other than non-valvular atrial fibrillation. 

In secondary prevention the patient has the disease and the objective is to reduce risk factors and to retard progression (e.g. aspirin and lipid-lowering drugs in atherosclerosis and post-myocardial infarction). In breast cancer, the use of tamoxifen, which can itself rarely cause endometrial cancer (which is detectable and treatable), raises complex scientific and socioeconomic issues. 

The treatment of myocardial infarction requires thrombolysis, aspirin and [i-adrenoceptor biockade acutely, with the latter two continued for at least two years as secondary prevention of a further myocardial infarction,... 

Aspirin, by covalently acetylating the active site of cyclooxygenase, blocks the production of TXAj from its major precursor, arachidonic acid. By causing this mild hemostatic defect, low-dose aspirin has been shown to be effective in prevention of acute myocardial infarction (see Clinical Comments). For Ivan Applebod (who has symptoms of coronary heart disease), aspirin is used to prevent a first heart attack (primary prevention). For Ann Jeina and Cora Nari (who already have had heart attacks), aspirin is used to prevent a second heart attack (secondary prevention). 

In contrast, indobufen (Fig. 31.15), a reversible but very potent inhibitor of platelet COX-1 activity, was shown to have comparable clinical efficacy to that of aspirin in prevention of DVT after myocardial infarction and in blocking exercise-induced increase in platelet aggregation (99). In the secondary prevention of thromboembolic events, 100 or 200 mg of indobufen twice daily is as effective as warfarin or aspirin in patients with or without atrial fibrillation (100). Currently, indobufen is only available for routine clinical use in Europe. 

Secondary prevention. In a meta-analysis of randomised, controlled studies in patients following myocardial infarction or acute coronary syndrome, intensive warfarin (INR greater than 2) plus aspirin 80 to 325 mg daily was associated with 2.5-fold increased risk of major bleeding, when compared with aspirin alone, although the actual incidence was low (1.5% versus 0.6%). This analysis excluded studies of coronary stenting, see (b) above. In another similar meta-analysis, combined use of aspirin and warfarin (INR 2 to 3) was associated with a 2.3 odds ratio of a major bleed, when compared with aspirin alone.The number needed to treat to cause one major bleed was 100. This compared with a number needed to treat to avoid one major adverse event (death, myocardial infarction or stroke) of 33. 

Antiplatelet (Aspirin) Therapy in Secondary Prevention of Myocardial Infarction (Ml) ... 

The anti-platelet effects of acetylsalicycUc acid, both in vitro and in vivo, were recognized long before the biochemical details of arachidonic acid metabohsm in platelets had been elucidated, and before the inhibitory effects of aspirin on cyclo-oxygenase were known (reviews, refs. 348-353). The drug had even been employed in large chnical trials as an anti-thrombotic agent, for example in attempts to prevent secondary myocardial infarction or stroke (for reviews, see e.g. refs. 

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