Return of the Wonder Drug : The Old Standby, Aspirin, Is Back in Vogue, but Is It Really All It’s Cracked Up to Be?

Once again, aspirin has come out of the medicine cabinet and into the limelight.

The recent spate of publicity apparently confirming its role in warding off heart attacks is, more than anything, testimony to the remarkable staying power of a drug first patented by Bayer in 1899, a year after the German pharmaceutical house introduced a promising new cough medicine called heroin.

Since then, aspirin--originally an extract from willow bark--has risen and fallen from therapeutic grace, and suffered and repelled challenges by newer pain relievers. Through it all, sensational claims have mixed with public confusion over its benefits and side effects.

National Study

The latest round of fascination with the drug, first introduced as a fever fighter, was set off last week by news of a still-incomplete national study of more than 22,000 U.S. American doctors who found that taking a 325-milligram tablet of the aspirin product Bufferin reduced the odds of having a heart attack.

Stores quickly reported increased sales and aspirin makers lobbied retailers to add to their inventories. All but obscured in the commotion was the fact that a Glendale ear, nose and throat doctor had pioneered much the same theory in the early 1950s.

Now as then, the public was quick to pick up on the good news while ignoring the downside. “I think the public is looking for easy ways out,” Dr. James Schoenberger, a prominent Chicago prevention expert, said of last week’s report. “They want the magic pill, the magic bullet to prevent them from ever getting a heart attack.”

But Schoenberger, like other experts, was quick to add: “If you’re going to do something like start taking aspirin when you’re 40, for the next 25 years, to prevent a heart attack, long-term effects of aspirin might be very important to you.”

Just what are the pluses and minuses of this wonder drug?

Aspirin’s staying power over the years has been primarily as a result of its versatility and low cost. Alex Savanian, an associate professor at the USC School of Pharmacy, said aspirin--now technically called acetylsalicylic acid--still offers such unique medicinal properties that it is likely to remain an important part of the pharmaceutical arsenal for at least the next 20 years.

This versatility, pharmaceutical experts agree, comes from aspirin’s combination of three major effects on body chemistry: It relieves pain, primarily because it is a highly effective anti-inflammatory drug that reduces pressure in blood vessels; it reduces fever, apparently by muting effects of the fever center in the brain; and it impairs the clotting action of platelets, thus reducing risk of stroke or heart attack.

But like virtually all drugs, aspirin achieves these benefits at a sometimes high price. Overdoses can be fatal and side effects include sometimes-serious bleeding, a possible worsening of ulcers and upset stomachs.

Pregnant women are advised not take aspirin. People with hypertension should use it only under a doctor’s care. And in children and teen-agers, it has such a high risk of causing the potentially fatal disorder called Reye’s syndrome that warning labels have been required since 1986 as a result of pressure by consumer health groups on the U.S. Food and Drug Administration.

The saga of aspirin’s transformation from pedestrian tenant of the medicine chest to perceived wonder drug counts among the stars of its cast the Glendale doctor who in 1956 published the first medical journal study concluding that two aspirins a day could prevent heart seizures and strokes.

Sensationalised at the time, the theory, proposed by Dr. Lawrence Craven, was for a time the talk of the Southern California medical community. Craven himself said he popped two pills every day in the belief it strengthened his heart. Craven said there had been no heart attacks among 1,465 patients to whom he recommended aspirin prevention therapy.

In language strikingly similar to headlines that greeted the release last week of the new study touting aspirin as a heart attack preventive, a tabloid in 1957 described Craven’s work as “the one-pill-a-day defense against heart attacks.” Aspirin, readers were told 31 years ago, was the “ ‘old’ wonder-drug with a new job.”

Discredited Idea

Ironically, Craven died a month later of a heart attack at age 74, and a physician friend recalled that his cause of death did much to discredit his maverick belief about aspirin.

“I know he (Craven) was taking two aspirin a day,” said Dr. Maynard Bourdeau, a Glendale physician, now nearly 80, who knew Craven. “We would talk about it and he said he was on it and, at the time, of course, that made people skeptical. People thought it was a little funny that such a simple thing as aspirin would do any good.”

But now, Bourdeau has started taking the advice seriously once again. “I’m on aspirin today,” he said. “I had a coronary six months ago. It’s a thing to do.”

Craven, it now appears, had been right. The chemical explanation of why was not developed until after his death.

In the late 1950s and early 1960s, scientists came to understand prostaglandins, the naturally occurring fatty chemicals in the body on which aspirin works. Prostaglandins are found in various body organs, including the prostate, brain, kidneys, lungs, pancreas and even seminal fluid. While many of the interactions of aspirin and the prostaglandins are still somewhat mysterious, enough is now known to permit scientific interpretation of the effects of the drug and its natural chemical predecessors that had been known to occur for centuries. (Willow bark as a fever treatment, for instance, had first been described scientifically by an English physician in about 1750 and the active ingredient, salicin, was isolated in 1829.)

“Essentially, aspirin inhibits the production of these prostaglandins,” said Dr. Earl Lockhart, medical director for Glenbrook Laboratories, the subsidiary of Sterling Drug, Inc., that produces Bayer aspirin in the United States.

In pain control, Lockhart said, aspirin appears to prevent formation of a type of prostaglandin that attacks pain-triggering tissue at a wound. As a pain killer, aspirin is called a “peripheral analgesic” in that its pain-relief effect occurs at the site of the injury and not at more central “receptor” sites on which more powerful analgesics, like morphine, have their primary action.

Aspirin’s performance in fever relief, said Lockhart, is far more theoretical. Prostaglandins exist in the central nervous system at the center of the brain, he said, near the location of the fever control center. Animal studies, he said, have established that aspirin prevents formation of the prostaglandins near the fever control center and it is theorized that this may explain the fever-control effect in humans.

Aspirin, Lockhart said, has also shown at least theoretical promise of being able to inhibit cataract formation in the eyes.

Complex Action

But it is aspirin’s anti-clotting effect that is perhaps its most significant and complex action. Loose in the bloodstream, said USC’s Savanian, aspirin binds itself to platelets to initiate the process recognized as clotting. Acting almost like a Teflon coating on the platelets, aspirin’s active ingredient makes any platelet with which it comes in contact permanently incapable of clotting.

Because myocardial infarctions and strokes occur when a clot breaks loose and damages the muscle tissue of the heart, in the case of heart attack, or the brain, in the case of a stroke, the clotting inhibition has the effect of being protective. But because the anti-clotting action is indiscriminate and pervades the entire bloodstream, aspirin’s greatest benefit is also its greatest potential danger. It can dangerously thwart the clotting action of a wound and, in combination with a natural tendency to irritate the stomach, aspirin can cause potentially catastrophic reactions in ulcer patients.

“I feel that is is going to be some time before we come up with a drug as widespread and effective as aspirin,” Savanian observed.

Second Study

The newest findings were published last week in the New England Journal of Medicine. Close on that study’s heels came preliminary results of a second study of more than 5,000 English physicians who did about the same thing. Those results were more ambiguous and did not show a clear-cut advantage for aspirin-taking, but the British researchers agreed the American results were probably correct.

Between 1983 and April of last year, two studies in groups of Veterans Administration patients found aspirin is able to protect against myocardial infarction in men with severe angina pectoris chest pain. Other research has identified aspirin as an aid in stroke prevention.

Since the original article by Craven was published in the Mississippi Valley Medical Journal, a number of large studies have linked aspirin to the prevention of heart attacks and strokes. In 1980, the Aspirin Myocardial Infarction Study, sponsored by the federal government’s National Heart, Lung and Blood Institute, found that taking aspirin was not clearly beneficial in preventing recurrence in patients who had previously had heart attacks. But several other studies at the time disagreed, and the doctor who led the original research on heart attacks now agrees that aspirin has heart attack/stroke preventive capability.

Many experts, though, fret that the newest publicity may set off a stampede in which the public starts taking massive quantities of aspirin without realizing the danger of complications while achieving only a modest reduction of heart attack risk.

Schoenberger, the veteran preventive disease researcher who led the Aspirin Myocardial Infarction Study, said he is satisfied that aspirin’s heart attack/stroke prevention capability has been confirmed. Schoenberger, of Rush Presbyterian-St. Luke’s Medical Center in Chicago, said, however, that studies of physician aspirin-taking may not be definitive since doctors and their behavior may not represent wide groups of people.

In any event, Schoenberger contended, aspirin’s preventive abilities may simply be perceived by the general public as a sure cure when no such thing exists.

‘This Is Not a Panacea’

“I think there’s a streak of Ponce de Leon in each of us. You don’t have to watch your diet or lose weight or quit smoking,” he said. “You just go along and take aspirin. Some (people) will do that. I would like to disabuse that idea. This is not a panacea. It’s also not innocuous. Even that small amount (325 milligrams every second day) can trigger reactions in (an aspirin-sensitive) individual.”

Dr. H. Daniel Lewis, of the Kansas City VA hospital and a leader of one of several VA aspirin-heart attack studies, said the new results, however, establish aspirin as qualifying for a major role in the prevention of some of the most serious illnesses known. “This new study,” he said, “is looking at people who don’t have any evidence of coronary artery disease.

“This is not a secondary prevention study. It is primary prevention.”

In terms of what the future may hold for aspirin, Dr. Jack Hirsch, of the McMaster University Faculty of Medicine in Hamilton, Ont., said several studies either about to be published or in the final stages of research are likely to expand aspirin’s frontiers significantly in the short term. Anticipated developments after the turn of the century, however, probably ensure that different chemicals will replace aspirin.

Hirsch said an English study, whose results are to be reported shortly, has apparently found that stroke prevention can be achieved as effectively with comparatively low doses of aspirin--about 300 milligrams a day--as with higher doses of 1,200. The finding may help make it possible to achieve effective prevention in some patients whose gastrointestinal reaction to aspirin makes them unable to use the drug now.

Both Hirsch and Savanian said researchers are now almost unanimous in their agreement that aspirin’s anti-clotting effects come from its interaction with an enzyme called cyclooxygenase. Hirsch said it appears likely that better understanding of this reaction will boost aspirin into a position as treatment of choice.

The wisdom of lining up at the drugstore counter to buy aspirin to take every day or two to prevent heart attack is still unestablished, Hirsch added, primarily because reduction in risk from aspirin-taking alone hovers only in the 20% to 50% range in most studies. An aspirin-taker, he noted, is not rendering himself or herself immune to heart attack or stroke, by any means.

Nevertheless, he said, “I think it’s worth doing if you’re over 45. I’ve been doing it. I’ve got to put my money where my mouth is.”