ASPIRIN: the best NSAID

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Physician's Health Study,aspirin lowers MI 76% (19880

Below is the study that propelled aspirin’s use for prevention of ischemic heart attacks. Five year study using 325 mg aspirin every other day, which is sufficient for most on aspirin to prevent long-term platelet action (reduce blood clotting). Aspirin arm of the trial stopped early for ethical reasons because of 76% of heart attack reduction, and thus allow the placebo group to voluntarily take aspirin. Death from an acute heart attack (“acute” means death from the initial heart attack and not second one or subsequent heart failure do to damage). The aspirin cohort had 10 deaths and the placebo 28. A higher dose would have both avoided the issue of becoming at least partially resistant to the platelet inhibition effect of aspirin and would slow atherogenesis and reduce cancer risk and death. Thus at 5 years if 325 mgs of aspirin were taken daily additional lives would have been saved from heart attacks and cancer. Over the 5 years there was an increased risk of ulcer with aspirin of 0.3% (39 excess ulcers in the group of the 11,035 using aspirin, age 40 to 84 at enrollment in 1982 ). If the dose is doubled or tripled the rate would be about double, and all would have an underlying issue of pylori or other bacteria that compromises the protective mucus membrane.
http://www.nejm.org/doi/full/10.1056/NEJM198907203210301#t=articleTop

Final Report on the Aspirin Component of the Ongoing Physicians' Health Study
Steering Committee of the Physicians' Health Study Research Group*

N Engl J Med 1989; 321:129-135July 20, 1989DOI: 10.1056/NEJM198907203210301

&#8220;The Physicians' Health Study is a double-blind, placebo-controlled, randomized trial designed to test two primary-prevention hypotheses in a population of healthy male physicians: whether aspirin in low doses (Bufferin, Bristol-Myers Products, 325 mg every other day) reduces mortality from cardiovascular disease, and whether beta carotene (Lurotin, BASF, 50 mg on alternate days) decreases the incidence of cancer. Every six months for the first year and annually thereafter, the participants were sent a supply of monthly calendar packs (provided by Bristol-Myers Products) containing white tablets (aspirin or placebo) for odd-numbered days and red capsules (beta carotene or placebo) for even-numbered days. They were also sent brief questionnaires asking about their compliance with the treatment regimen and the occurrence of any relevant events. By January 25, 1988, the participants had been followed for an average of 60.2 months (range, 45.8 to 77.0); 99.7 percent were still providing information on morbidity, and the vital status of all 22,071 doctors was known. The reported consumption of aspirin or other platelet-active drugs was 85.71 percent in the aspirin group and 14.23 percent in the placebo group. A total of 1269 physicians (624 taking aspirin and 645 taking aspirin placebo) requested an enteric-coated preparation (supplied by Bristol-Myers Products), and an additional 29 (16 assigned to aspirin and 13 assigned to placebo) specifically requested Ecotrin or its placebo (supplied by Smith-Kline Beckman). Although the beta carotene component of the trial is continuing at least through 1990, the Data Monitoring Board recommended the early termination of the blinded aspirin component of the trial on December 18, 1987. This decision was based on all available evidence, including three major considerations: the presence of a significant (P<0.00001) reduction in the risk of total myocardial infarction among those in the aspirin group;&#8230; There were 139 myocardial infarctions among those assigned to aspirin and 239 among those assigned to aspirin placebo (relative risk, 0.56; 95 percent confidence interval, 0.45 to 0.70; P<0.00001) (Table 1). This represents a 44 percent reduction in risk, and the benefits of aspirin were significant for both fatal and nonfatal myocardial infarction. In terms of absolute rates of events, the figures can be extrapolated to 254.8 per 100,000 per year in the aspirin group and 439.7 per 100,000 per year in the placebo group&#8230;. Altogether, 11,037 physicians were assigned at random to receive aspirin and 11,034 to receive aspirin placebo&#8230;. Further analyses showed that the reduction in the risk of myocardial infarction was apparent only among those who were 50 years of age and older. The benefit was present at all levels of cholesterol, but appeared greatest at low levels. The relative risk of ulcer in the aspirin group was 1.22 (169 in the aspirin group as compared with 138 in the placebo group&#8230; For cholesterol, the beneficial effects of aspirin were apparent at all levels. The observation that the benefits of aspirin for myocardial infarction were greatest at low levels of cholesterol was unexpected&#8230;.. Most recently, the Second International Study of Infarct Survival17 evaluated the role of aspirin in evolving myocardial infarction in a randomized trial with 17,187 participants and demonstrated a 49 percent reduction in nonfatal myocardial infarction, a 46 percent decrease in nonfatal stroke, and a 23 percent reduction in cardiovascular death after five weeks. All these reductions were statistically significant&#8230; cardiovascular mortality rate among the physicians in this trial was only 15 percent of that expected for a general population of white men with the same age distribution over a similar period&#8230;[From table 1.. Total heart attacks aspirin cohort 139, placebo 238, or 1/3rd of heart attacks in the aspirin group, and 2/3rd placebo groups.]

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