Aspirin 'resistance' linked to increased CV morbidity

Aspirin 'resistance' linked to increased CV morbidity

By Caroline Price

18 January 2008

Br Med J 2008; Advance online publication

MedWire News: Patients who do not respond to aspirin therapy are at increased long-term risk for cardiovascular (CV) morbidity, the results of a systematic review and meta-analysis show.

Such patients, labeled "aspirin resistant," had an approximately four-fold increased risk for nonfatal and fatal cardiovascular, cerebrovascular, or vascular events when taking aspirin compared with those classified as sensitive to aspirin.

"Not only did aspirin resistance have an effect on clinical outcome but this risk was not ameliorated by currently used adjunct antiplatelet therapies," the study authors note.

It is not clear why a significant number of CV disease patients derive no benefit from aspirin therapy, nor how these patients may be identified, explain Michael Buchanan (McMaster University, Hamilton, Ontario, Canada) and colleagues.

Such patients have been termed aspirin resistant because their platelets are not affected in the same way as platelets from individuals who seem to benefit from aspirin therapy. Yet it remains unknown whether these patients simply receive too low an aspirin dose, are not compliant, have differing abilities to absorb aspirin, or have an underlying genetic disposition that makes aspirin ineffective. Furthermore, few studies have addressed the impact of aspirin resistance on clinical outcomes.

To look for any relationship between aspirin resistance and clinical outcomes, Buchanan and team reviewed the literature and conducted a meta-analysis on 20 studies involving 2930 patients with CV disease who were receiving aspirin as an antithrombotic. Patients were classified as aspirin resistant if their platelet response was not inhibited in vitro by aspirin.

Overall, 810 (28%) patients were classified as aspirin resistant. These patients, regardless of underlying clinical symptoms, had a greater risk for death, acute coronary syndrome, failure in vascular intervention, or a new cerebrovascular event.

Indeed, 39% of aspirin-resistant compared with 16% of aspirin-sensitive patients had any cardiovascular event, giving an odds ratio of 3.85 (p<0.001).

The odds ratios for acute coronary syndrome, graft failure, and new cerebrovascular event in aspirin resistant compared with aspirin sensitive patients were 4.06, 4.35, and 3.78, respectively.

Moreover, the odds ratio for mortality for aspirin resistant patients was 5.99 (p<0.003).

A planned sensitivity analysis revealed no evidence of a dose-response relationship between aspirin resistance and any cardiovascular outcome among patients who received aspirin alone or who received a second antiplatelet. Furthermore, patients who were aspirin resistant had no benefit from concomitant therapy with clopidogrel or tirofiban, or both.

Italian cardiologists Giuseppe Biondi-Zoccai (University of Turin) and Marzia Lotrionte (Catholic University, Rome) commented in an accompanying editorial that further trials are needed to clarify whether aspirin resistance is just a nonmodifiable risk factor, or whether more aggressive antithrombotic regimens will benefit patients with aspirin resistance.

However, they cautioned that although clinical trials will help "fill in the gaps," there may be another factor generating interest in aspirin resistance.

"Drug companies may be keen to downgrade aspirin from its leading role as an effective drug in CV disease so that they can substitute it with much more expensive but marginally more effective alternatives," they stated.

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