But it is most likely to mean that high-risk patients - who are also probably those who have been taking a long-term course of aspirin and have developed a tolerance to it - simply aren’t responding to it anymore, no matter how much they take.
And what about those healthy people who are taking aspirin for vague preventative purposes? A recent study of healthy volunteers found that their platelets did not respond well to low-dose aspirin; to be effective, a dose of at least 500 mg/day is required (Circulation, 1997; 95: 63-8).
But, as we already know, high doses of aspirin are linked to a higher incidence of side-effects such as gastrointestinal and cerebrovascular bleeding (Circulation, 2002; 105: 1650-5; Hellenic J Cardiol, 2004; 45: 1-5). Clearly, the potential benefits of aspirin need to be weighed against these risks and the risks of the known side-effects of any alternative drugs.
The clopidogrel connection
One such alternative, clopidogrel (Plavix), is a more expensive antiplatelet agent widely prescribed for atherothrombotic disease. It is often used with aspirin to maximise antiplatelet benefit. The Clopidogrel in Unstable Angina to Prevent Recurrent Events (CURE) trial showed that heart patients treated with both aspirin and clopidogrel within 24 hours had a 20 per cent relative-risk reduction in vascular events compared with aspirin alone (N Engl J Med, 2001; 345: 494-502). However, there was also an increased risk of major bleeding with clopidogrel.
But, in a randomised blinded trial of clopidogrel vs aspirin in patients at risk of ischaemia (CAPRIE), clopidogrel proved more effective in reducing cardiovascular risk than aspirin (Lancet, 1996; 348: 1329-39). So, for patients who respond poorly to aspirin, clopidogrel may yet be a better option as it works in a slightly different way.
Nevertheless, as with aspirin, clopidogrel resistance has been reported (Thromb Haemost, 2003; 89: 783-7; Am J Cardiol, 2003; 91: 1123-5). Looking at both drugs together, resistance is seen in more than half the patients chronically taking either aspirin or clopidogrel (Curr Cardiol Rep, 2005; 7: 242-8).
Physicians are now in a bind. Faced with a high-risk and potentially aspirin-resistant patient, they can either prescribe the more expensive treatment in addition to aspirin (increasing the risk of serious side-effects), or they can remove aspirin from the cocktail and rely on clopidogrel - and risk resistance to it instead, and still have the possibility of bleeding.
And should both drugs be offered to all patients, or should clopidogrel or the other, new antiplatelet agents be used only in cases of apparent aspirin-resistance? Given that most cardiovascular patients are already on potentially interacting medications such as ACE inhibitors and statins, it seems imprudent to prescribe anything remotely unnecessary.
To test or not to test?
Lab tests such as the platelet-function analyser PFA-100® use blood samples to measure platelet reaction on exposure to aspirin, and may be useful for identifying aspirin resistance in some patients (Thromb Haemost, 2000; 83: 316-21). AspirinWorks is a test that measures levels of thromboxane in the urine - low levels mean the aspirin is working.
But medical opinion is divided as to whether aspirin testing should be routine for high-risk patients. Those against the idea believe that more facts on the mechanism of aspirin resistance are needed. They also question the validity of test results.