The Pharmaceutical Journal
Vol 270 No 7246 p572
26 April 2003

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Letters to the Editor

Low-dose aspirin

Researchers made alarmist suggestion

From Mr J. Barber

The news report on the possible lack of efficacy of low-dose and enteric coated aspirin requires clarification (PJ, 22 February, p258).

The researchers from the Northwestern Memorial Hospital, Chicago, were trying to correlate the phenomenon of "aspirin resistance" with aspirin dose and formulation.¹ Aspirin resistance is not fully understood and is poorly defined; "aspirin non-responders" may be a better term. There are conflicting reports on its incidence and the clinical relevance of this phenomenon is uncertain.

Your report on this study suggested that there were two patient groups, one on low-dose aspirin, ie, 81mg daily, with the other group on medium dose, ie, 325mg daily. This was not the case. The group on low-dose aspirin (n=39) included three patients on 162mg daily and 36 on 81mg aspirin, either daily or alternate day dosing. The medium dose aspirin group (n=87) were on either 325mg daily or 650mg daily. Furthermore, the report by Alberts does not indicate what doses the patients getting enteric coated and uncoated aspirin were receiving. It is not clear from the presentation that in comparing the two different formulations, there was also a comparison of identical doses. Until this detail is reported more fully, or the study replicated in an adequately powered patient group, it cannot be concluded that some patients on low-dose or enteric coated aspirin are not achieving adequate levels of platelet function inhibition.

Current platelet function tests have been recognised as having limitations, especially with regard to aspirin. Platelet aggregation measured with conventional ex vivo methods, including collagen and noradrenaline induced aggregation, has been demonstrated to have significant inter- and intra-individual variability. These ex vivo tests cannot be considered to correlate with clinical events and outcomes.²

A study of the effect of aspirin dose and enteric coating on platelet reactivity in volunteers found that there was no difference between low (81mg) and medium (325mg) dose aspirin on platelet reactivity.³ However, there was a difference in collagen lag time (a measure of platelet aggregation) but the clinical significance of this was not established, although it was postulated only to be of significance in acute coronary syndrome (ie, unstable angina, acute myocardial infarction).

A more recent study investigated the effect of low-dose (81mg) enteric coated aspirin on platelet function after seven days treatment in healthy volunteers.⁴ Serum thromboxane B₂, arachidonic acid and collagen-induced platelet aggregation inhibition were measured and compared with baseline were found to be 97.4, 97.9 and 70.9 per cent inhibited, respectively (compared with 7.8, –1.0 and 2.7 per cent, respectively, for placebo).

Well-designed clinical trials have shown that aspirin is an effective antiplatelet agent when used in doses ranging from 50mg to 100mg daily, with some evidence to suggest that doses as low as 30mg daily may be effective in patients with a history of transient ischaemic attacks.² The Dutch study failed to show any difference in efficacy between regimens of 30mg and 383mg aspirin daily. Furthermore, the evidence for alternate day dosing, as used by Alberts et al, is limited. The Physicians' Health Study of the use of aspirin for primary prevention of cardiovascular events (note, aspirin is not licensed for this indication in the UK although it is recommended in some guidelines) investigated a dose of 325mg aspirin on alternate days. At an average follow up time of five years, it was found that this regimen reduced the risk of the first myocardial infarction by 44 per cent. The Women's Health Study in over 40,000 US female health workers is currently investigating a regimen of 100mg on alternate days. Results from this study are expected soon.

Although the research presented by Alberts et al may be of interest, it is alarmist to suggest that current low-dose, enteric coated regimens are ineffective based on this study when one considers that the doses of coated and uncoated aspirin used in each patient group were not published (it is not even clear that identical doses were compared) and that the study was insufficiently powered.

John Barber
Medical Information Manager
Alliance Pharmaceuticals Ltd

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