Life Extension - Treatment using Medicine

Aspirin - updated: 23 February 2009

Lifelong aspirin supplementation as a means to extending life span

Rejuvenation Res. 2004 Winter;7(4):243-51

Phillips T, Leeuwenburgh C.

Arising from an initiative by the National Institute of Aging (NIA) requesting novel proposals challenged with increasing lifespan and longevity, our laboratory has generated a hypothesis to test the efficacy of lifelong, low-dosage aspirin administration as a means to achieving this goal. The intervention testing program (currently underway) proposing aspirin as an anti-aging agent evolved from the multitude of properties encompassed in aspirin and the potential of these attributes to prevent the cellular and functional declines, particularly from inflammatory and oxidative sources, evidenced to contribute to aging. Aspirin is a widely administered, cheap, anti-inflammatory, and antioxidant compound that has a variety of positive effects on the immune system and cardiovascular health. Notably, aspirin may affect oxidant production, cytokine responses, and block glycooxidation reactions, thus posing it as a triple threat against the symptoms of aging. Whether aging is molded by interplay between oxidative stress and inflammatory mediators has received little attention; however, we and other laboratories have explored this notion and have observed an elevated inflammatory status with age. Stemming from these observations and in view of the limited success of antioxidant therapies in improving lifespan in long-lived species, in this article we propose a protocol to examine life-long use of a very low dose anti-inflammatory compound such as aspirin to engage the inflammatory and endogenous oxidative insults accompanying aging and, in so doing, attempt to increase maximum and mean life span.

Publication Types:

• Review

Adherence to aspirin in the prevention of myocardial infarction. The Physicians' Health Study

Arch Intern Med. 1994 Dec 12-26;154(23):2649-57

Glynn RJ, Buring JE, Manson JE, LaMotte F, Hennekens CH.

BACKGROUND: The primary aim of this article was to explore, in subgroup analyses, whether participants with differing frequencies of aspirin consumption in a randomized, double-blind, placebo-controlled, primary prevention trial had different magnitudes of benefit in the prevention of myocardial infarction. Secondary aims were to identify factors associated with adherence and to examine the relationship of adherence with cardiovascular outcomes in the placebo group. METHODS: The Physicians' Health Study randomized 22071 US male physicians who were free of myocardial infarction and cerebrovascular disease at baseline. The average follow-up during the aspirin component of the trial was 60.2 months. Baseline cardiovascular risk factors and adherence to therapy during the trial were assessed by questionnaire; cardiovascular outcomes were reported by questionnaire and confirmed by record review by an Endpoints Committee. RESULTS: Several cardiovascular disease risk factors assessed at baseline were related to poor adherence (taking < 50% of study tablets): cigarette smoking, obesity, lack of exercise, and history of angina. After adjusting for baseline differences in risk factors, participants in the aspirin group with excellent adherence (taking at least 95% of study tablets) had a statistically significant 51% reduction in myocardial infarction compared with those with excellent adherence in the placebo group. Those in the aspirin group with poor adherence had a smaller, non-significant reduction in risk of myocardial infarction (a 17% reduction associated with taking < 50% of study tablets). In the placebo group better adherence was not associated with decreased risk of myocardial infarction, but was strongly associated with decreased risk of death. CONCLUSIONS: These subgroup data raise the possibility that a less than alternate day aspirin regimen may yield lower benefits in the prevention of myocardial infarction. Alternate explanations are that these analyses reflect either the play of chance or effects of uncontrolled confounding since comparisons were no longer randomized. Randomized trials are necessary to address the question of frequency of administration of aspirin to achieve optimal benefits in primary prevention of myocardial infarction.

Publication Types:

• The Physicians' Health Study randomized 22071 US male physicians

Prevention of myocardial infarction and stroke by aspirin: different mechanisms? Different dosage?

Thromb Res. 1998 Sep 15;92(1 Suppl 1):S7-12

More than 50 randomized trials have documented the efficacy and safety of aspirin as an antiplatelet agent and a cardiovascular drug. However, the optimal dose for preventing coronary and cerebral thrombosis has long been a cause of debate. For patients with ischaemic heart disease the range recommended for the prevention of a secondary event, based on strong clinical evidence, is 75-160 mg aspirin/day. For patients with cerebrovascular disease, recommendations range from 30-1300 mg/day. If these patients require a higher dose of aspirin it suggests that a different mechanism of action is involved. This paper considers hypotheses and reports the findings of recent clinical trials. The SALT study compared aspirin with placebo in 1360 patients with TIA or minor ischaemic stroke. It showed an 18% reduction in the risk of stroke or death in patients receiving 75 mg aspirin/day. Five other trials of 55,000 patients with ischaemic cerebrovascular disease compared the protective effect of aspirin (range 30-300 mg/day) with placebo, clopidogrel, or oral anticoagulants. Aspirin was better than placebo, safer than oral anticoagulants, and no different from clopidogrel. The implications of these findings are discussed. Mechanistic studies and randomized clinical trials strongly suggest that the mechanism of action and dose requirement of the antithrombotic effect of aspirin in patients with cerebrovascular disease is the same as that for ischaemic heart disease.

Publication Types:

• Review

Low-dose aspirin and vitamin E in people at cardiovascular risk: a randomised trial in general practice. Collaborative Group of the Primary Prevention Project

Lancet. 2001 Jan 13;357(9250):89-95

de Gaetano G; Collaborative Group of the Primary Prevention Project.

BACKGROUND: In addition to the treatment of specific cardiovascular risk factors, intervention which interferes with the general mechanisms of atherosclerosis could further reduce the incidence of cardiovascular events. We aimed to investigate in general practice the efficacy of antiplatelets and antioxidants in primary prevention of cardiovascular events in people with one or more major cardiovascular risk factors. METHODS: We did a randomised controlled open 2x2 factorial trial to investigate low-dose aspirin (100 mg/day) and vitamin E (300 mg/day) in the prevention of cardiovascular events, in people with one or more of the following: hypertension, hypercholesterolaemia, diabetes, obesity, family history of premature myocardial infarction, or individuals who were elderly. FINDINGS: 4495 people (2583 female, mean age 64.4 years) were included in the trial. After a mean follow-up of 3.6 years the trial was prematurely stopped on ethical grounds when newly available evidence from other trials on the benefit of aspirin in primary prevention was strictly consistent with the results of the second planned interim analysis. Aspirin lowered the frequency of all the endpoints, being significant for cardiovascular death (from 1.4 to 0.8%; relative risk 0.56 [95% CI 0.31-0.99]) and total cardiovascular events (from 8.2 to 6.3%; 0.77 [0.62-0.95]). Severe bleedings were more frequent in the aspirin group than the no-aspirin group (1.1% vs 0.3%; p<0.0008). Vitamin E showed no effect on any prespecified endpoint. Analyses were by intention-to-treat. INTERPRETATION: In women and men at risk of having a cardiovascular event because of the presence of at least one major risk factor, low-dose aspirin given in addition to treatment of specific risk factors contributes an additional preventive effect, with an acceptable safety profile. The results on vitamin E's cardiovascular primary preventive efficacy are not conclusive per se, although our results are consistent with the negative results of other large published trials on secondary prevention

Publication Types:

• randomised controlled open 2x2 factorial trial

Publication Types:

• Review