Aspirin and Statins to Decrease Risks of Cardiovascular Disease - The Need for Wider Utilization

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US Cardiology 2004;2004:1(1):1-3

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While the proximate cause of virtually all acute cardiovascular disease (CVD) syndromes is thrombosis, the principal underlying cause is atherosclerosis.1

With respect to aspirin, in basic research this drug irrepressibly acetylates the active site of cyclo-oxygenase in platelets which inhibits thromboxane A2, a powerful promoter of aggregation.2 In randomized trials of secondary prevention and their meta-analyses, aspirin reduces risks of myocardial infraction (MI) by about one-third, stroke by about a quarter, and CVD death by about one-sixth.3 In randomized trials of primary prevention and their meta-analyses, aspirin significantly reduces risk of first MI by about one-third and all important vascular events by about one-sixth.4 The US Preventive Services Task Force5 and the American Heart Association (AHA)6 have recommended aspirin for all apparently healthy individuals whose risk of a first coronary heart disease (CHD) event is 6% or 10% respectively.

With regard to statins, in basic research these drugs decrease total and low-density lipoprotein (LDL) cholesterol as well as trigylcerides and also increase high-density lipoprotein (HDL) cholesterol. In the early trials of secondary and primary prevention, the benefits of a reduction in coronary events of about one-third, as well as stroke and total mortality by about one-fourth, appear to emerge after one to three years, which are compatible with a primary atherogenic effect of the statins.7 More recent trials have raised the possibility of early clinical benefits due to pleiotropic effects that may include acute antiplatelet mechanisms.8,9

The fact that aspirin and statins have such different biological mechanisms of action suggests that their beneficial effects on CVD would be at least additive.10,11 For several reasons, the anti-inflammatory effects of both aspirin and statins may contribute to the beneficial effects on CVD. First, C-reactive protein (CRP), a sensitive marker of inflammation, predicts future risks of CVD.12,13 Second, the benefits of both aspirin and statins on CVD seem to be modified by underlying inflammation. Third, both these agents reduce CRP levels.

With respect to aspirin and CRP, the totality of evidence includes observational epidemiological data within two randomized trials12,13 and a randomized cross-over trial in chronic stable angina.14 All three trials antedated the availability of statins. In the PhysicianÔÇÖs Health Study12, 22,071 apparently healthy men aged 40-84 years without prior MI or stroke, were randomized to 325mg aspirin or placebo every other day.

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