We do not know who should be given what dose and for how long

As a result of the findings of the aspirin study discussed in another newsletter article this week (An Aspirin a Day May Not Keep the Doctor Away) and editorial appeared in the same issue of the British Medical Journal (BMJ), with the same title and subtitle as above. Dr. Martin R Tramèr of Geneva University Hospital in Switzerland discusses the issue of aspirin use at some length, even including some historical facts, such as:

Thromboxanes are a group of substances known as eicosanoids that are produced from arachidonic acid by the action of an enzyme known as cyclooxygenase. Thromboxane A2 is powerful aggregator of platelets and also a vasoconstrictor.

Dr. Tramèr notes that this "blood thinning" or antithrombotic effect of aspirin is actually an adverse reaction of the drug.

He notes that beginning with a 1991 report in the Archives of Internal Medicine, it has been suggested that aspirin should be given to all men aged 50 years or older and to all women after the menopause. However, Dr. Tramèr notes two reasons why this "enthusiasm needs to be dampened":

Firstly, aspirin, through its ability to block the synthesis of prostaglandins, may damage the gastrointestinal mucosa. Erosions may be trivial, but they may progress to ulcers, which in turn may bleed or perforate, and may even kill. This happens more often than many doctors like to believe.

Secondly, reduced thrombus formation results in a greater tendency to bleed. Thus, in a patient who is taking aspirin any ulcer that may arise may bleed even more extensively. 

In light of these potential dangers, therefore, many physicians have logically aimed to use the minimum dose of aspirin that inhibits thrombus formation, on the assumption that this would also minimize the risk of gastrointestinal complications. This is the rationale behind the use of daily low dose aspirin to prevent heart disease.

However, Dr. Tramèr notes that the latest systemic review published by the BMJ provides strong evidence that these previous assumptions may have been incorrect. He notes that the study found "no evidence of dose responsiveness over a wide range of doses (50 to 1500 mg/day)."

Dr. Tramèr notes that in the physician's health study, a large randomised trial of 11,037 patients given aspirin 325 mg every other day for 60 months, as many as 3.6% had symptoms of hematemesis (the vomiting of blood) or melena (blood in the stools).

Referring to the current study, Dr. Tramèr states that "the most important message in Derry and Loke's paper is that there is no gain without pain."

Unfortunately, the study leaves more questions than answers, such as "Who should be given what dose of aspirin, and for how long?" to which he tries to shed some light:

• "In patients with a history of stroke or transient ischemic attack, the minimal effective dose of aspirin to prevent further vascular accidents remains unknown."

British Medical Journal November 11, 2000; 321: 1170-1171