Clinical impact of aspirin resistance

The failure of daily aspirin therapy to achieve an adequate or ‘normal’ suppression of platelet aggregation, as assessed ex vivo, is known as ‘aspirin resistance’.1 2 A substantial fraction of patients classified as aspirin-resistant are in fact poorly compliant.3 In other cases, an increase in platelet turnover, often seen in association with systemic inflammation, as found in smokers and patients with diabetes, may render a once-daily administration schedule inadequate.2 4–6 (Administering aspirin twice daily can result in greater platelet inhibition but may increase the risk for gastrointestinal bleeding.) When adverse pharmacokinetic factors impede the delivery of aspirin to platelets, an increase in dose can be helpful.7 8 Concurrent administration of ibuprofen or other cyclooxygenase-1 (COX-1) inhibitors may prevent aspirin from acetylating the active site of COX-1.9 But in some patients, even when platelet cyclooxygenase is fully inhibited, platelet aggregation remains anomalously high; this might be described as inherent aspirin resistance. Inherent aspirin resistance presumably reflects genetic or metabolic factors that alter the expression or function of platelet proteins such that platelets can aggregate effectively in the absence of thromboxane.

Although low-dose daily aspirin regimens reduce the risk for cardiovascular events by about 25% in patients with cardiovascular disease,10 meta-analyses found that subjects who were resistant to ongoing aspirin therapy, as opposed to those who were sensitive, are about three times more likely to experience cardiovascular events.11 12 This greatly increased risk is disproportionate to the benefit achievable with aspirin treatment, and evidently reflects the fact that aspirin resistance is serving as a marker for metabolic factors, which themselves greatly increase cardiovascular risk. Nonetheless, there is strong evidence that intensified platelet-stabilising therapy can markedly improve outcomes in patients diagnosed with aspirin resistance. A number of controlled trials have defined groups of patients who are resistant to …