28 Ana Laynez and Ron Waksman MedStar Washington Hospital Center, Washington, DC, USA Chronic stable angina (CSA) is the most common manifestation of ischemic heart disease in the developed world and is associated with impaired quality of life and increased mortality. It is a clinical syndrome, sometimes disabling, characterized by chest, jaw, shoulder, back, or arm discomfort related to stress or exercise that terminates with rest or nitroglycerin administration, generally the expression of an imbalance between myocardial oxygen demand and supply. When the angina appears with effort and with no changes in its onset in the last month, the angina is classified as stable, and it implies no complications or unfavorable evolution in an immediate future. The effective management of this highly prevalent condition is largely dependent on the identification of the prevailing pathogenic mechanism, the implementation of lifestyle changes, and the appropriate use of pharmacological agents and revascularization techniques. Medical treatment must be focused on symptoms release and, basically, on the improvement of patient prognosis by reducing the incidence of thrombotic complications, such as acute myocardial infarction (MI) and death. The first meta-analysis that analyzed the efficacy of aspirin in coronary artery disease, including patients with CSA, included 145 trials and 29 treatment comparisons. It was published by the Antithrombotic Trialists’ Collaboration and studied patients with different vascular entity. It concluded that the use of 75–325 mg/day of aspirin during a long period of time was efficient against MI, death, and stroke [1]. Later, in 2002, a new meta-analysis with 287 studies issued up to 1997, was published. 212,000 patients were analyzed, including patients with CSA. It concluded again that aspirin, as an antiplatelet agent, protects most of the population at high risk of ischemic vascular events [2]. Seven studies with patients with CSA stand out in this meta-analysis (Table 28.1). The most important one, the Swedish angina pectoris aspirin trial, with 2035 patients with CSA treated with sotalol for symptoms control, studied the effect of 75 mg aspirin compared to placebo [8]. This was the first prospective study to show the beneficial effect of aspirin in the reduction of MI and death in CSA. Those patients under aspirin showed a 34% reduction in primary events (MI and sudden death; 95% CI, 24–49%; p = 0.003) compared to patients under placebo and a reduction in secondary events (vascular events, vascular death, death by any reason, stroke) from 22% in the group with placebo compared to 32% in the group having aspirin. Table 28.1 Aspirin in CSA studies. Previously, 22,071 male medical doctors with no previous history of acute MI, stroke, or TIA were studied in a double-blind randomized study, where the effect of 325 mg of aspirin in primary prevention was analyzed [9]. From the whole studied population, 333 patients with CSA were analyzed in a posterior substudy. They were randomized into two groups whether they received aspirin 325 mg or placebo, and the effect of the aspirin in secondary prevention was analyzed. Those patients treated with aspirin presented a total reduction of primary event (first MI) of 12.9% compared to 3.9% in the placebo’s group (relative risk (RR), 0. 30; 95% CI, 0.14–0.63; P = 0.003) [10]. ACT trial [2] also provided a valuable information related to the effect of different doses of aspirin in patients at high risk of cardiovascular (CV) events. Different groups depending on the dose used were compared (<75 mg, 75–150 mg, 160–325 mg and 500–1500 mg). A similar risk reduction in CV events was observed when the different groups were compared against each other, not seeing significant differences between low and high doses of aspirin in terms of effectiveness. That led to conclude that with similar results, a lower dose is preferable in terms of avoiding bleeding complications. Few studies from the meta-analysis used doses of less than 75 mg of aspirin, so no final conclusions on this dose could be made. A minority of patients develops hypersensitivity to aspirin, manifested clinically in different situations, such as respiratory tract disease or urticaria and angioedema [11, 12]. The main adverse effect of aspirin is an increased risk of bleeding mainly from the gastrointestinal (GI) tract but also very rarely intracranial bleeding. It is important to recognize patients with higher risk of bleeding and to consider an alternative antiplatelet agent for them. In the US Preventive Services Task Force report on the use of aspirin for the primary prevention of CV disease, the magnitude of increase in risk was approximately two to three times higher in patients with a history of GI ulcer and twice as high for men as women [13]. It is assumed that between 5.5% and 60% of patients treated with aspirin may develop a degree of aspirin resistance, depending on the definition used and parameters measured [14]. Aspirin resistance could clinically refer to patients with maintained ischemic events despite appropriate use of aspirin. Patients who are not compliant with aspirin therapy or those who are not prescribed with aspirin when clinically indicated could be also considered as aspirin resistant. The effect of the interaction with other medical agents could be also interpreted as resistance. In the laboratory, aspirin resistance suggests the inability of the drug to achieve a specific level of platelet inhibition in ex vivo
Antiplatelet Therapy in Stable Coronary Artery Disease
Introduction
Aspirin
Study
N
Patient population
Aspirin mg/day
Follow-up
Cardiff-I [3], 1974
1239
Men with a prior MI
300
13 months
Danish Low Dose [4], 1988
301
Prior carotid endarterectomy
50–100
23 months
UK-TIA [5], 1991
1620
Prior TIA or minor stroke
300
50 months
SALT [6], 1991
1360
Prior TIA or stroke
75
32 months
ESPS-2 [7], 1996
3298
Prior TIA or stroke
50
24 months
SAPAT [8], 1992
2035
CSA
75
50 months
Doses
Side effects and aspirin resistance
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