DAVID TODD July 16 1990



DAVID TODD July 16 1990




Ever since Carl Stephenson began experiencing chest pains four years ago, his life has undergone important changes. Tests showed that Stephenson, a chemical engineer with Calgary-based Esso Resources Canada Ltd., was suffering from a partial blockage of the coronary artery, a condition that made him a prime candidate for a heart attack. Since then, he has worked hard at cutting his risks: he exercises more and eats less fat. Stephenson also takes a daily dose of a drug widely used as a heart attack preventive: acetylsalicylic acid (ASA). Stephenson, 60, who takes his ASA in the form of a coated tablet called Entrophen, says that he decided to try regular doses of ASA in 1988 after a study in the United States showed that taking the common household pain reliever—commonly called Aspirin—on a regular basis almost halved the risk of heart attack in a survey group made up of healthy, middle-aged male physicians. His own doctor expressed approval of the idea. Said Stephenson: “I always thought of Aspirin as something to take for headaches. I was amazed to find it had other benefits as well.”

Staple: For most of the 20th century, ASA (in Canada, the name Aspirin is a registered trademark of Aurora, Ont.-based Sterling Drug Ltd.) has been a staple in household medicine cabinets. Indeed, according to industry analysts, Canadian^ in 1989 swallowed more than one billion Aspirin and generic ASA tablets to deal with complaints that ranged from head colds and influenza to assorted aches and pains. But the drug, which in its generic form costs only about 2 cents per pill, may be capable of far more than reducing fevers and soothing everyday headaches. In recent years, medical

researchers have found evidence to suggest that ASA can play a significant role in preventing and treating heart attack and stroke. And despite the development of newer and more expensive drugs, ASA is still routinely used to reduce the pain and inflammation of rheumatoid arthritis.

Some studies have suggested that regular doses of ASA may also lessen the frequency and severity of migraine headaches, which afflict as many as one in five Canadians. In addition, studies are under way that could lead to the use of ASA in strengthening the immune system in some patients. Said Dr. John Cairns, a cardiolo-

gist who is chairman of the department of medicine at McMaster University in Hamilton, Ont.: “Aspirin really is a wonder drug. It's amazing what it does and how cheap it is.” Inroads: Despite ASA’S remarkable versatility, newer types of pain-killers, such as Tylenol and Nuprin, which do not contain ASA—and which do not possess ASA’s apparently wide range of benefits—have made heavy inroads into the nonprescription painkiller market. As a result, the share of the market held by Aspirin and ASA dropped from 68 per cent in 1982 to 26.3 per cent this year as rival pharmaceutical firms wage a

bitter battle for market share (page 42).

Despite its wide range of useful medical properties, ASA does have certain drawbacks. Its side effects include possible stomach upsets (caused by the acid in ASA irritating parts of the stomach lining) and excessive bleeding in a small number of people (because ASA thins the blood). As a result, physicians caution people against popping tablets daily without medical

supervision. Since 1980, medical re_

searchers have found evidence linking the drug to the development of Reye’s syndrome, a rare but sometimes fatal disorder that primarily affects the brain and liver. The syndrome has struck children and teenagers with viral infections such as influenza and chicken pox. According to Allan Gee, a spokesman for the Reyes Syndrome Foundation of Canada, “We haven’t had a report of a case for nearly three years, since the warning label went on ASA products in October, 1987.”

Warning: And doctors warn pregnant women not to take ASA, because it may cause excessive bleeding in mother or baby during delivery, as well as prolonging labor in some births. Earlier this month, the U.S.

Food and Drug Administration (FDA) in Washington announced that a strengthened warning would be required on ASA products advising women to avoid ASA, particularly in the last three months of pregnancy, because of possible fetal blood circulation problems and other complications. FDA officials in Washington said that the new warning was partly

prompted by recent studies carried out at the National Institutes of Health in Bethesda, Md. Since 1986, Ottawa has required Aspirin and ASA products to carry a warning advising women to consult their doctors before using ASA during the last three months of pregnancy.

As well, Dr. Mark Adams, an associate professor of rheumatology at the University of Calgary, said that U.S. studies have found

indications that ASA may thin human cartilage and accelerate the development of osteoarthritis, a degenerative disease that affects victims’ joints. Said Adams: “ASA can have some pretty severe side effects. I wonder if, with what we know today, ASA could have become an over-thecounter drug.”

Roots: Still, as a growing body of research attests, the humble ASA tablet is also uncommonly rich in medical potential. The drug’s roots stretch back more than 2,000 .years. A natural chemical cousin, salicin, occurs in the bark of the willow tree, and according to ancient accounts, the Greek physician Hippocrates in the fifth century BC recommended chewing willow bark to lessen pain and fever. But it was not until 1853 that a French chemist, Charles Frederick von Gerhardt, synthesized acetylsalicylic acid, a chemical in which

salicin is a basic component.

Four decades later, Felix Hofmann, a research chemist for the German pharmaceutical firm of Friedrich Bayer & Co., demonstrated ASA’s usefulness as a pain reliever by producing it in a laboratory and then having a colleague test it on Hofmann’s father, who was suffering from rheumatoid arthritis. In 1899, Bayer started mass-producing and marketing the drug, initially in powdered form, under the trade name Aspirin.

Most of the attention focused on ASA during the past 15 years has been prompted by growing evidence that the drug can help prevent heart attacks and strokes in some people. William Anderson, 42, an Ottawa-based RCMP staff sergeant, underwent surgery for a severe angina condition six years ago. On his doctor’s advice, Anderson has for the past four years taken one ASA tablet every night. Said Anderson: “I never used ASA before the surgery. If I had a headache or something, I would just wait for it to go away. Now, this is part of my life.”

Uses: In 1971, Sir John Vane, a scientist working at the Wellcome Research Foundation laboratories in Beckenham, England, made important new discoveries about acetylsalicylic acid that led researchers to find new uses for ASA in inhibiting the formation of blood clots, which can block coronary arteries and lead to heart attacks. Ivy Dix, a 59-year-old Brantford, Ont., woman who runs a small business making floral arrangements, began taking an ASA tablet a day in June as a stroke preventive. Routine tests had revealed several areas in Dix’s brain in which scar tissue indicated a blockage of the blood vessels feeding the brain. Dix says her physician recommended ASA as a precautionary measure to lessen the likelihood of further


clotting that could lead to stroke. Said Dix: “I’ll probably have to take it for the rest of my life, but I don’t mind.”

In 1988, an international study of 17,187 patients headed by British researchers reported a 42-per-cent reduction in the mortality rate among patients taking ASA and a clot-dissolving drug called streptokinase shortly after the onset of a heart attack. The study, conducted over a 36-month period, also showed that by itself, ASA reduced deaths by 23 per cent. Said McMaster University’s Cairns of the study: “The significance is profound. It’s almost unprecedented to have such overwhelmingly positive results.” Julie Buring, an assistant professor of preventive medicine at Boston’s Harvard University, said that the result of the study showed that “if you take an ASA tablet at the time of a heart attack, you will reduce your chance of dying from that heart attack, or getting another one.”

Preventive: Evidence concerning ASA’S ability to prevent strokes is equally impressive. Approximately 80 per cent of all strokes result from clots that block blood vessels supplying the brain. Because ASA can prevent such clotting, Dr. Henry Barnett, scientific director of the autonomous John P. Robarts Research Institute in London, Ont., says that the drug is now a standard stroke-prevention treatment for patients who have suffered either a previous stroke or a stroke warning known as a transient ischemic attack, sometimes described as a “mini-stroke.” Indeed, a 1978 study headed by Barnett was one of the first major studies to establish that regular doses of ASA could reduce the risk of stroke in patients who had experienced transient ischemic attacks.

More recent research in the United States has suggested another way that ASA may help people who are considered at risk from strokes. In March, a study by a group of 15 U.S. universities and medical centres published in The New England Journal of Medicine found

that the drug halved the risk of strokes in patients with a heartbeat irregularity called atrial fibrillation. The condition, which occurs in at least one per cent of people over the age of 60, causes blood clots to form in the atria, or upper chambers, of the heart and can lead to ischemic strokes. The drug warfarin, which inhibits blood clotting, is sometimes used to treat atrial fibrillation. But warfarin requires monthly blood monitoring and may cause internal bleeding. Dr. Robert Hart, an associate professor of medicine at the University of Texas Health Science Center in San Antonio, and one of the researchers involved in the study, said that ASA may offer an alternative treatment. Added Hart: “It’s safe, inexpensive and potentially effective. What could be better?”

Debate: Still, some issues involving ASA and heart disease are the subject of heated debate among medical researchers. Physicians widely acknowledge the drug’s value in preventing second heart attacks. But there are unanswered questions about ASA’s role in heading off first heart attacks. The focus of debate is the Physicians’ Health Study—the trial that sparked Calgarian Carl Stephenson’s interest in ASA. The study, carried out between 1981 and 1987, involved 22,071 healthy male physicians with no previous history of serious ^ heart trouble. The research-

ers, from Boston’s Harvard

University Medical School

and Brigham and Women’s

Hospital, published the final

results last July. Their con-

elusion: one ASA tablet every

other day reduced the risk of a first heart attack for healthy males over the age of 50 by 44 per cent. During the study, half of the participants were given a low dose of ASA every other day, while the rest were given a placebo (a nonmedicinal tablet).

But the Harvard researchers appended some cautionary notes to their report. Their study showed that, while lowering heart attack risk, an ASA tablet every other day also increased slightly the risk of a hemorrhagic stroke (caused when a blood vessel bursts, allowing blood to flow into the brain). Harvard’s Buring told Maclean ’s that no one should take ASA to ward off heart attacks without first consulting a physician. Said Buring: “It’s not something that people should just pop every day.”

Risks: As well, another recent study said that some risks may be associated with the use of ASA to prevent first heart attacks. In November, a research team from the University of Southern California School of Medicine in Los Angeles reported the results of a survey involving almost 14,000 residents of the Leisure World retirement community in Laguna Hills, Calif., southeast of Los Angeles. The study found that men who took ASA daily did have a slightly reduced risk of a first heart attack.

But Annlia Paganini-Hill, who headed the study, said that ASA users with no previous history of heart problems also ran a significantly greater risk of ischemic heart disease. For their part, the Harvard researchers criticized the California study on the grounds that it was based on a questionnaire rather than a controlled clinical trial. Said Buring: “I don’t think that observational data is as compelling as trial data.”

While some cardiologists now say that they are satisfied that ASA can help stave off a first heart attack in middle-aged men who have been diagnosed as having heart disease, others, because of the risks involved, remain cautious about ASA’s role in heart attack and stroke prevention. And doctors who do prescribe ASA for heart patients say that taking ASA regularly does not eliminate the need for such preventive measures as exercise and better eating habits. They add that for people with no apparent heart attack risk factors, the small possibility of side effects—including stomach upset and, in rare cases, internal bleeding—may outweigh the preventive benefits.

Still, Dr. Henry Mizgala, a professor of medicine at the University of British Columbia, says that he has been taking an ASA tablet every other day for the past three years to prevent

heart attack. Even though Mizgala says that he has never experienced chest pains or other symptoms, his father had coronary disease and Mizgala says that he is a strong advocate of ASA “as a primary prevention tool” for people with heart problems. Said Mizgala: “In my experience, ASA is overwhelmingly accepted to be very safe and very, very effective.”

In recent years, medical researchers have gained a greater understanding of how and why ASA is useful in treating or preventing so many illnesses. The key lies in ASA’s effect on the human body’s production of prostaglandins, a

family of hormone-like chemicals. What Sir John Vane discovered was that acetylsalicylic acid blocks the body’s production of prostaglandins, which play a role in a wide range of basic bodily functions, including blood clotting, immune response and kidney function. Scientists say that its ability to block the production of prostaglandins may enable ASA to prevent blood from clotting and to soothe fever and arthritis symptoms.

Migraine: Some researchers say that the effect of ASA on prostaglandins may also make the drug useful in preventing migraine headaches. Findings from the U.S. Physicians’ Health Study, released in February, showed that there were about 20 per cent fewer reports of migraine among participants in the study who regularly took ASA compared with the control group that did not. Although researchers disagree about the underlying cause of migraine, there is evidence that the headaches start when a type of blood cell called platelets cling together, releasing a chemical

called serotonin that causes blood vessels in the victim’s head to constrict. Some scientists say that by inhibiting the prostaglandins involved in the process, ASA may be able to prevent the onset of migraine headaches.

Some headache specialists now prescribe the drug as a preventive for many of their migraine patients. Dr. Arthur Elkind, director of the Elkind Headache Centre in Mount Vernon, N.Y., says that he has given ASA, in doses of a half-tablet a day, to about 30 migraine sufferers during the past four years, with considerable success. Said Elkind: “Many patients who’ve used it say they had fewer headaches than before, and less severe headaches.”

There is also evidence to suggest that ASA may improve the performance of the human immune system. Dr. Judith Hsia, an assistant professor of cardiology at the George Washington University School of Medicine and Health Sciences in Washington, says some prostaglandins inhibit the production of the natural immune agents interleukin-2 and interferon. By blocking the production of prostaglandins, ASA may help the body fight off infection. In 1988, Hsia tested the drug’s effect on a group of 19 student volunteers who had received a dose of rhinovirus, which causes the common cold. The students on ASA still got colds but they also had increased levels of the immune agents. Hsia said that while ASA alone is not a particularly potent immune modifier, it could prove useful in combination with other drugs.

Data: Meanwhile, scientists are exploring other possible medical applications of ASA. Studies at Yale University in New Haven, Conn., and at England’s Oxford University, have suggested that ASA may be useful in preventing the formation of cataracts, a clouding of the lens of the eye that can lead to blindness. Researchers involved in the Physicians’ Health Study are currently examining the data amassed from their research subjects for evidence to show that ASA can help prevent the disorder. Other researchers, from the Harvard School of Dental Medicine, are interested in studying the Physicians’ Health Study data to see if there is any evidence that the compound might help prevent periodontal disease, an inflammation of the gums and connective tissues supporting the teeth.

On the basis of the medical applications that have already been found, ASA ranks as one of the most widely used and versatile drugs ever discovered. Indeed, considering all of the benefits, and side effects, of ASA, Dr. James Wright, a pharmacologist and specialist in internal medicine at the University of British Columbia’s University Hospital, says that “if ASA were coming on the market today, it would definitely be a prescription drug.” As it is, ASA is the little pill that resides in medicine cabinets, drawers and glove compartments— an unsung wonder drug that may help Carl Stephenson and thousands of others live longer.