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 What Doctors Don't Tell You: Special Report: Aspirin resistance - When the risks outweigh the benefits 
What Doctors Don't Tell You © (Volume 16, Issue 6)

The US Food and Drug Administration’s Cardiovascular and Renal Drugs Advisory Panel doesn’t support the use of aspirin for the primary prevention of heart attacks. In other words, there is insufficient evidence to suggest that healthy people should routinely ingest aspirin ‘just in case’. Yet, despite the lack of solid proof that the drug will work for them, 23 per cent of healthy Americans are voluntarily taking low doses of aspirin regularly in the belief that it will reduce their risk of heart attack and stroke. These individuals tend to be health-conscious and physically active (MMWR, 1997; 46: 498-502).

Aspirin resistance: the evidence According to the clinical and laboratory evidence, between 5 and 60 per cent of aspirin-takers experience a ‘variable’ response (or resistance) to aspirin (Pharmacotherapy, 2005; 25: 942-53). Such aspirin resistance, even in a healthy population, translates to a greater than threefold increase in the risk of adverse events (J Am Coll Cardiol, 2003; 41: 961-5).

Even more worrying, a recent study found that, while two months of aspirin treatment markedly reduced the potential for blood clotting, its effect on platelets successively decreased from that point on.

In other words, long-term aspirin treatment is associated with a progressive loss of platelet sensitivity to the drug. The study followed patients for two years, after which blood clots were significantly more likely to occur than they had been at aspirin’s peak-performance period of two months (J Am Coll Cardiol, 2004; 43: 979-84).

This may explain why a significant proportion (approximately one in eight) of high-risk patients will suffer ‘breakthrough’ events within two years, despite regular aspirin intake (Indian Heart J, 2003; 55: 217-22).

It also makes sense of a study that found that angina patients previously on long-term aspirin treatment were 20 per cent more likely to have a recurrent event within six months compared with patients not previously on aspirin therapy (Am J Cardiol, 1999; 83: 1147-51).

To make matters worse, current smokers and patients with diabetes, previous stroke, heart failure, high blood cholesterol or coronary artery disease - all those who are most at risk of cardiovascular events - are the ones who are more likely to develop aspirin resistance (Rev Med Chil, 2005; 133: 409-17; Thromb J, 2004; 2: 1; Acta Diabetol, 2005; 42: 99-103; Am J Health Syst Pharm, 2005; 62: 1398-405).

Disputed dosages Aspirin resistance is more likely to occur when patients with coronary artery disease take less than 100 mg/day, which produces fewer side-effects, compared with 150 mg/ day or 300 mg/day (Am J Med, 2005; 118: 723-7). An earlier study found that while 25 per cent of cardiovascular patients were initially resistant to aspirin even at the relatively high dose of 325 mg/day, that percentage dropped to just 8 per cent when the dose was increased to 1300 mg/day (Stroke, 1994; 25: 2331-6). These data appear to suggest that a high dose is more effective.

If only it were that simple. A meta-analysis found that high-dose aspirin (500-1500 mg/day) was no more effective than low doses (75-150 mg/day) in reducing vascular events in high-risk patients (J Am Coll Cardiol, 2003; 41: 966-8). This could mean that aspirin doesn’t exert its antithrombotic effects as an antiplatelet inhibitor, but through some other mechanism.

It could also suggest that researchers and clinicians still aren’t sure how aspirin really works, which is why aspirin resistance is a particularly frustrating phenomenon.

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What Doctors Don't Tell You What Doctors Don’t Tell You is one of the few publications in the world that can justifiably claim to solve people's health problems - and even save lives. Our monthly newsletter gives you the facts you won't......more
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