Aspirin for Stroke Prevention

Aspirin has been a pain-reliever for more than 100 years. And while most of the popular remedies used in the 19th century have been abandoned, the use of aspirin has increased.

This powerful pill, bought for one cent off the shelf of a grocery store, will reduce pain, fever, inflammation, prevent blood clots, and even reduce the risk of heart attacks and stroke.

Aspirin helps decrease blood clotting by chemically altering little cells in the blood called platelets. Platelets act to promote and form clots when they receive messages within the blood. If the message to act comes from a cut on the skin, that is good. But if the message is from the inner wall of an artery, the resulting blood clot can be bad, causing stroke or heart attack.

Since 1967, pioneering trials' confirmation of aspirin's value in these common disorders has come from nearly 300 studies involving 135,000 patients. The Antithrombotic Trialists' Collaboration, located in Oxford, England, has performed an analysis of all these trials (a strategy defined as a meta-analysis) comparing benefit to patients taking placebo.

The conclusion for patients at risk for stroke was that the relative risk of an attack was reduced about 25 percent. After the occurrence of an acute stroke, nine fewer vascular events occur with the use of aspirin for three weeks in 1,000 patients.

An Old Standby

In the more than 35 years since aspirin's potent anti-clotting effects were first discovered, relatively few drugs have been developed that can even be compared to the efficacy, ease of use, and price of aspirin. From the meta-analyses, and to many stroke experts and biostatisticians in this field, aspirin remains the drug of choice.

Extensive advertising has been promoting three other prescription drugs, also platelet inhibitors, which have similar anti-clotting effects. They are: ticlopidine (Ticlid), clopidogrel (Plavix), and dipyridamole with very small doses of aspirin (Aggrenox). Ticlopidine's use is now known to have been associated with at least 260 deaths from blood disorders. Because of this danger, in conjunction with the drug's relatively small benefit over aspirin, Ticlopidine is no longer recommended by many physicians, but is still on the market.

Evaluation of Plavix in a single large trial with stroke patients was not significantly better than aspirin in reducing further strokes, and the company has twice been cautioned by the FDA to NOT promote the drug as though it were better than aspirin.

Finally, the large meta-analysis appearing in the January 2002 issue of the British Medical Journal concluded that "addition of dipyridamole to aspirin produced no significant further reduction in vascular events compared with aspirin alone."

And while these drugs may be no better than aspirin, it is good to have alternative platelet inhibitors in case aspirin is not tolerated or fails to prevent further events. Only then will this writer consider the alternative of Plavix. Generic dipyridamole combined with over-the-counter aspirin could also be used if aspirin proves ineffective for the individual patient.

The Price We Pay

The monthly drugstore cost of aspirin is about $1 compared with between $95 and $150 for Plavix and Aggrenox respectively. If these drugs were substantially better than aspirin, the cost would be bearable.

Ticlid, priced in a New York drugstore in September 2001 at $130 for a month's supply, should not be used regardless of cost because of its known link to fatalities.

Aspirin, and all platelet inhibitors may cause bleeding with gastrointestinal bleeding of sufficient concern that patients with recent peptic ulcers should not take aspirin and no one should take it long-term without medical supervision. The enteric-coated variety causes less gastric irritation.

One day we hope to have an even more effective antithrombotic. Meanwhile, aspirin is the drug of first choice.

H.J.M. Barnett, OC, MD, FRCP(C), DSc(Hon.) is Professor Emeritus at the University of Western Ontario, and a scientist with The John P. Robarts Research Institute