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The use of drugs in cardiovascular medicine is like fashion - always changing. The use of Acetylsalicylic Acid (ASA or Aspirin) taken in a small dose daily, has been advocated for many years to reduce the risk heart attacks and strokes. ASA is a platelet inhibitory drug, effective in doses as low as 50 mg per day. The 2008 policy? ASA has benefits in the primary and secondary prevention of heart attacks in men with less benefit in younger women. Aspirin has a benefit in women over the age of 65 in the prevention of stroke. All people who have a transient cerebral ischemic attack should start ASA
prevention therapy. Background One major shift in recommendations is based on noticing differences among men and women of different ages. Ridket and Beller pointed out that 95,000 men and women participated in aspirin prevention trials with a net 24% reduction in myocardial infarction and no benefit on stroke; however if you stratify men and women separately, you get 44,000 men with 32% reduction in heart attack. In contrast the 51,000 women had little or no reductions in myocardial infarction, but a significant 19% reduction in the risk of stroke. A further study looked at the experience of women over the age of 45 more closely. A total of 39,876 women participated in the trial to receive aspirin 100 mg very other day or placebo. The mean follow-up period was 10.1 years. The primary endpoint was first major cardiovascular event, which included nonfatal MI, nonfatal stroke, or cardiovascular death. Secondary endpoints were the individual endpoints of fatal or nonfatal MI, fatal or nonfatal stroke, ischemic stroke, hemorrhagic stroke, and death from cardiovascular causes. Additional analyses included the incidence of death from any cause, transient ischemic attack (TIA), and the need for coronary revascularization. The characteristics for the groups were similar; participants were 54.6 years of age and more than half were postmenopausal; slightly more than one-quarter were hypertensive and nearly 85% had a 10-year Framingham risk score < 5%. Ridket stated: “Women over the age of 65, have a benefit of stroke reduction associated with low-dose aspirin. In women under age 65, my feelings are go to the gym, lose weight, eat a healthy diet, and maybe the benefit of aspirin is just smaller than we had hoped.” ASA inhibits the cyclo-oxygenase enzyme in platelets leading to reduced formation of prostaglandin G2, the precursor of thromboxanes. Two hours after oral administration, ASA inhibits blood thromboxane A2 generation and arachidonic acid (AA)-induced platelet aggregation . The ASA effect on circulating platelets is long-lasting, so that small daily doses sustain the effect. ASA has limitations. ASA blocks the synthesis of thromboxane A, but has no effect on thromboxane-independent mediators of platelet activation, such as adenosine diphosphate, thrombin and serotonin. Up to 30% of people with coronary artery disease are unresponsive to ASA, when the inhibition of platelet activation and aggregation and bleeding time is measured.
Ridker PM, Cook NR, Lee IM, et al. A randomized trial of low-dose aspirin in the primary prevention of cardiovascular disease in women. N Engl J Med 2005 352:1293-1304.
Sabatine, Marc S., Cannon, Christopher P., Gibson, C. Michael,
Lopez-Sendon, Jose L., Montalescot, Gilles, Theroux, Pierre, Claeys,
Marc J., Cools, Frank, Hill, Karen A., Skene, Allan M., McCabe,
Carolyn H., Braunwald, Eugene, the CLARITY-TIMI 28 Investigators,
Addition of Clopidogrel to Aspirin and Fibrinolytic Therapy for
Myocardial Infarction with ST-Segment Elevation N Engl J Med 2005
Published online [ Diener HC, Darius H, Bertrand-Hardy JM, Humphreys M; European Stroke Prevention Study 2. Cardiac safety in the European Stroke Prevention Study 2 (ESPS2). Int J Clin Pract 2001;55(3):162-3 |
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