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Arterial Disease

Some Topics

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Anti-platelet therapy

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 growing list of contradictory studies is more evidence of drug companies determined to control the marketplace, rather than good science and is clearly not good public policy. Buyer beware. To create markets for more expensive, prescription platelet inhibitors, inexpensive, over the counter ASA must be discredited. A similar battle for market share is occurring with hydrochlorothiazide and inexpensive diuretic that is widely prescribed as the first drug of choice to lower blood pressure.

What is the best self management policy? You might agree that ASA has benefits in the primary and secondary prevention of heart attacks in men with less benefit in women younger than 55. 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. ASA should be taken by people who have had a heart attack or a stroke.

Background

One major shift in recommendations was 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.

  • The caveat here is the enteric coated ASA is less effective than plain ASA and that higher doses are less effective than lower doses.

  • The easiest and least expensive preparation to take is plain ASA, children's size, not enteric coated.

  • The popular anti-inflammatory drug, Ibuprofen, inhibits the antiplatelet effect of ASA.

  • ASA should be taken one hour before taking ibuprofen or 8 hours after taking ibuprofen to preserve the antiplatelet activity of ASA.

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., et al. Addition of Clopidogrel to Aspirin and Fibrinolytic Therapy for Myocardial Infarction with ST-Segment Elevation N Engl J Med 2005 Published online www.nejm.org March 9, 2005

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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