Many of those who donate blood to the hospital take low-dose aspirin (acetylsalicylic acid, ASA) pr

Fråga: Many of those who donate blood to the hospital take low-dose aspirin (acetylsalicylic acid, ASA) prophylactically as self-medication in prevention of heart disease. Is there any documentation confirming the effects of such medication in persons who have no or have not had any heart disease? Blood from these donors is not given to children, and neither thrombocytes nor plasma is used from it.

Sammanfattning: A more or less regular intake of aspirin is common among a considerable part of the population. Different studies have also demonstrated a prolonged bleeding time in relation to so-called low-dose aspirin. Doses as low as 75 mg or 50 mg/day have been shown to have this effect. To what extent this contributes to the overrepresentation of bleeding complications shown in different long-term studies with aspirin used prophylactically is not yet clear. Also a continuous intake of ASA in low doses for a longer period of time cannot be looked upon as being without risks, particularly in individuals with a predisposition for heart and vascular diseases.

Therefore, low-dose aspirin formulations registered in Sweden are available only for prescription by physicians and should not be used for longer periods of time without physician ordination on the above-mentioned indications.

Svar: Low-dose aspirin is defined somewhat differently internationally. In the US and UK a dose of aspirin less than 300 mg a day is usually defined as low-dose (1). Generally, a dose of less than 100 mg a day of acetylsalicylic acid is regarded in Sweden as low-dose ASA, based on studies in which increasing doses of aspirin were administered with measurements at the same time of prostaglandin and prostacyclin metabolites in the blood or the urine and where a discriminative effect on these parameters could be demonstrated (2). At the same time it should be pointed out that doses of aspirin used for pain relief are between 500 and 1000 mg in a single dose.

In studies concerning SECONDARY PROPHYLAXIS with aspirin after myocardial infarction and stroke, daily doses between 30 mg (3) and 1500 mg (4) have been used. In such placebo-controlled studies, it has been possible to show a statistically significant secondary prophylactic effect at different dose levels. Appearance of adverse effects, especially gastrointestinal, including bleeding, have been dose-related. In addition, in most of the studies, there has been an overrepresentation of individuals with fatal as well as non-fatal bleeding in the group of patients treated with active substance without reaching statistical significance (4,5).

The use of aspirin for PRIMARY PREVENTION, meaning intake of aspirin prophylactically without the appearance of MI or stroke, has been studied in two trials. Slightly more than 5000 male doctors, between the ages of 50 and 78 years, were included in the British Doctors Trial of an open design in which half of the participants avoided ASA and the other half had a daily intake of 500 mg (6). After an average treatment period of six years there was no statistically significant difference between the two treatment groups with regard to vascular death, stroke or myocardial infarction taken together or for any of these events separately. Possibly, disabling strokes were somewhat more common in the aspirin-treated group. Only limited information was available concerning whether the strokes were of bleeding or thrombotic origin. The other study, The US Physicians Health Study (9), was a double-blind, placebo-controlled study with a dose of 325 mg ASA every other day. 22071 male American physicians in the age group 40-84 years were included with a mean follow-up time of five years. In the groups with the diagnoses vascular death, stroke and myocardial infarction, there was a statistically significant reduction of the events in the ASA-treated group. In a more detailed analysis, myocardial infarction (fatal or non-fatal) demonstrated the most pronounced reduction of 44 per cent, which also meant that the study was stopped in advance. However, there was no difference in other types of myocardial death and a non-significant increased risk of strokes of all kinds, particularly in a rather small subgroup of haemorraghic strokes. To sum up: together these two studies of aspirin used for primary prevention demonstrate a 32 per cent reduction of non-fatal myocardial infarction and a 30 per cent reduction of combined vascular events and a non-significant increase of non-fatal strokes. Thus, a secondary prophylactic effect with low-dose aspirin can be regarded as documented whereas for primary prophylaxis it has still to be shown.

In different studies it has been shown using in vivo/in vitro techniques that doses of aspirin as low as 50 mg/day (7) may prolong bleeding time, which is probably a risk factor for the increased frequency of bleeding complications as observed in the clinical studies (10).

Intake of acetysalicylic acid is common in the general population at dosages for pain relief. In a parallell study group of 67 patients in the SALT study it could be demonstrated by determinations of S-TXB2 (stable metabolite of thromboxane) during the run-in period that about 1/3 of the patients had a more or less regular intake of ASA (8).