Long-Term Aspirin for Coronary Artery Disease Dependent on Biased Evidence?
John GF Cleland
Authors and Disclosures
Posted: 04/15/2010; Future Cardiology. 2010;6(2):141-146. © 2010 Future Medicine Ltd.
Abstract and Introduction
- Aspirin Fallacies: Is there a Sound Biological Rationale for Aspirin?
- Is Long-term Aspirin Therapy Effective?
- Is Aspirin Safe?
- Is the Correct Dose of Aspirin Known?
- Is Aspirin an Appropriate Background Therapy for Other Anti-thrombotic Agents?
- Has the Introduction of New Treatments Altered the Efficacy of Aspirin?
- Is Aspirin Free from Commercial Interest?
Abstract and Introduction
http://www.medscape.com/viewarticle/719632 A recent meta-analysis concluded that considerable uncertainty exists regarding the wisdom of giving aspirin for the prevention of a first vascular event in populations who are at a low or intermediate cardiovascular risk. This meta-analysis did not include three recent primary prevention trials[2–4] – these were resoundingly neutral or showed evidence of harm. A substantial segment of the medical community was surprised at this, with their reactions ranging from disbelief to anger. However, they would not have been surprised had they carefully read the original reports used by the meta-analysis and considered other relevant studies, such as the Pulmonary Embolism Prevention trial (n = 13,356), which showed a 33% increase (hazard ratio: 1.33 [95% CI: 1.00–1.78]; p = 0.05) in the risk of fatal or nonfatal myocardial infarction in patients who were assigned to receive aspirin rather than placebo after a hip fracture (an elderly group of patients who had a high prevalence of occult coronary disease).
The Antiplatelet Trialists recently stated that:
"Low-dose aspirin is of definite and substantial net benefit for many people who already have occlusive vascular disease."
However, this organization has strongly promoted aspirin use and stifled any contrary opinion. The data entered into this meta-analysis are different from those reported in the trials themselves. Changing the data after a study is complete is incorrect and may cause bias.
Many doctors have been deceived by biased reporting in the literature, which is a blight on the editorial reputation of many of the most eminent medical journals.[7,8] It is not clear whether editors were duped by cleverly written manuscripts or were seduced by preconceived notions regarding the efficacy of aspirin. However, the aspirin story is now unraveling. Guideline groups on both sides of the Atlantic no longer recommend aspirin use in patients with heart failure, even if they have coronary disease.[10,11] It is likely that further trials will be conducted to either refute or confirm the safety and efficacy of long-term aspirin use in other clinical settings. Those promoting aspirin as part of a 'polypill' approach to cardiovascular risk should be alert to these issues and, if they are genuinely concerned about patients' well-being, clinical science should be at the forefront of designing appropriate randomized placebo-controlled trials in order to demonstrate the safety and efficacy of the aspirin component. …
Aspirin Fallacies: Is there a Sound Biological Rationale for Aspirin?
All hypotheses depend upon perspective. If coronary events are initiated by platelet aggregation and thrombosis, then it does make sense to use aspirin. On the other hand, if events are triggered by hemorrhage into plaque, an anti-thrombotic agent sounds rather dangerous. Plaque hemorrhage, rupture and thrombosis are likely to be inextricably intertwined for vascular occlusion-initiating events and plaque hemorrhage may be an important component of plaque growth. There is moderately compelling evidence that low-dose aspirin accelerates the progression of atheroma.[13,14] Once an event has occurred, most patients will develop an ulcerated plaque and thrombus, providing a theoretical substrate for the short-term benefit of aspirin. Once the ulcer has healed, continued aspirin therapy may impair vessel wall defences against further events by blocking vasodilator prostaglandin production, thereby neutralizing any antiplatelet effects, explaining the neutral outcome in most long-term studies of aspirin and an increase in coronary events in some. Logically, aspirin should be given until the vascular ulcer has healed and should then be stopped. Unfortunately, theoretical reasoning is a poor guide to the effects of drugs in clinical practice. Only clinical trials can tell which theories work in practice, and even then, the mechanism of benefit may not be clear. The aspirin data are entirely consistent with a benefit from a short-term course (4–12 weeks) of aspirin after a coronary event, after which the aspirin can and perhaps should be stopped in order to maximize benefit. …