Aspirin - the versatile drug

[David Baxter PhD]

Aspirin: the versatile drug
CBC News
Thursday, May 28, 2009

Some say Aspirin's a wonder drug, your basic "ounce of prevention" that can ward off a lot of the ills that can plague you later in life.

Aspirin is the brand name for a drug called acetylsalicylic acid (ASA) ? a member of a family of chemicals called salicylates. ASA is one of the most commonly used drugs and billions of tablets are produced every year.

There are currently at least 50 over-the-counter medications available in pharmacies in which ASA is the principal active ingredient. It has always been touted as an effective painkiller.

Aspirin's been around for more than a century. It was developed in the late 19th century by Felix Hoffman, a young German chemist, who was looking for a drug that would help treat his father's arthritis. Most arthritis drugs at the time were from the salicylates family. But the problem with salicylates is they irritate the lining of the stomach.

Hoffman's search for a less acidic formulation culminated with ASA, which appeared to do the trick. Hoffman's employers, Friedrich Bayer & Company, were at first skeptical of the drug's commercial viability. They feared the drug's side effects ? shortness of breath, rapid heart rate at high doses ? would be a problem.

Still, Bayer marketed ASA under the name Aspirin. The company held the worldwide patent until it expired in the United States in 1917. Aspirin lost its status as a registered trademark in France, Russia, the U.S. and the United Kingdom as part of war reparations after the First World War.

But Bayer still holds the trademark in 80 countries, including Canada. That means ? in Canada ? the word "Aspirin" must be capitalized. ASA refers to generic versions of the drug.

What's it used for?
Just about everything these days, it seems.

It was developed as a painkiller and was mainly marketed as a headache medication or to treat the aches and pains of cold and flu. It takes fairly high doses for Aspirin to relieve pain.

By the middle of the 20th century, ASA's popularity declined with the release of acetaminophen and ibuprofen.

But in the early 1970s, British scientist John Vane and his colleagues published research that would change his and Aspirin's fortunes. His research showed how the drug works: it's what's known as a COX-2 inhibitor. COX-2 - an enzyme ? can be found in lots of normal tissue. But it's produced in even greater quantities in damaged tissue. With enough of the enzyme present, your brain tells you to feel pain. Aspirin prevents the enzyme from doing that job.

The research earned Vane a Nobel Prize in medicine in 1982.

What else does Aspirin do?
In low doses, it can help slow down the formation of blood clots. This can be useful for people at risk of stroke or heart attack. By the early 1980s, Aspirin began to be marketed as more than just a headache pill.

According to Health Canada, Aspirin is "indicated for the relief of pain, fever and inflammation of a variety of conditions such as influenza, common cold, low back and neck pain, dysmenorrhea, headache, toothache, sprains and strains, fractures, myositis, neuralgia, synovitis, arthritis, bursitis, burns, injuries, following surgical and dental procedures."

Based on its ability to thin the blood, Health Canada says Aspirin is also indicated for reducing the risk of:

• A first non-fatal heart attack in people deemed at risk by their physicians. The agency notes there's no evidence Aspirin will help ward off a first heart attack that is fatal.
• Stroke.
• Venous thromboembolism (blood clots) after total hip replacement.
• Deep vein thrombosis ? so called "Economy Class Syndrome" ? the formation of blood clots in deep veins. The name was coined after a woman died from a blood clot after a long flight in a cramped seat. Mixed research

Over the past few years, studies have suggested ASA may also help reduce the risk of:

• Colorectal cancer
• A common form of breast cancer
• Pre-eclampsia, a pregnancy disorder
• Stroke

Those studies suggested Aspirin appears to inhibit the process that could lead to pre-cancerous cells similar to the way it prevents those COX-2 enzymes from making you feel pain.

But this research is in the very early stages and scientists say wide studies are needed before any definitive results are available.

Some studies suggest Aspirin may help ? even prevent ? Alzheimer's disease, again by targeting those COX-2 enzymes.

However, some recent studies haven't been as glowing about the potential benefits of aspirin.

A study published in the October 2008 British Medical Journal found that Aspirin did little to prevent heart attacks in diabetics.

A study published in the April 11, 2009, edition of The Lancet concluded that while there's some evidence of Aspirin's potential protective effects when it comes to colorectal cancer, more evidence is needed to determine if it has benefits for other cancers. That, the study found, presents a dilemma: more evidence can only come from long-term trial, and one of Aspirin's side effects is increased risk of bleeding. So safer forms of the drug need to be developed.

A month later, another study published in The Lancet found that long-term use of Aspirin may be of little net benefit. The study concluded that while ASA can reduce the risk of non-fatal heart attacks by a fifth in people with no history of relevant disease, it will increase the risk of internal bleeding by a third. However, the benefits do outweigh the risks if you already have occlusive vascular disease.

Are there side effects?
Aspirin can cause upset stomach in some people, especially those who take it in high doses over a prolonged period to treat rheumatoid arthritis. The stomach problems can include ulcers and stomach bleeding.

Aspirin's anti-platelet activity has also been blamed for hemorrhagic strokes, caused by bleeding into the brain, in a small but significant number of people who use the drug regularly.

Some people may be unable to metabolize even small amounts of Aspirin. They can show symptoms that resemble an allergic reaction, such as hives, swelling and headaches.

The use of Aspirin is also not recommended for fevers in children since research has suggested that Aspirin given to kids with flu, chickenpox or other viral sicknesses may cause a potentially deadly problem called Reye's syndrome.

Aspirin overdose can be fatal. A potentially lethal dose is greater than 500 mg per kg of body weight. In cases of acute overdose ? when a single large dose is taken ? the mortality rate is estimated at two per cent.

In cases of chronic overdose ? where higher than normal doses are taken over a long period of time ? up to 25 per cent of cases can be fatal.

 

[David Baxter PhD]

Aspirin's risks outweigh benefits for healthy people

Aspirin's risks outweigh benefits for healthy people: review
CBC News
Thursday, May 28, 2009

Healthy people shouldn't take Aspirin to prevent heart disease, a new review suggests.

Aspirin and ASA are generally recommended to prevent non-fatal heart attacks among people who already had a heart attack or stroke. But the value of its long-term use by healthy people is uncertain, given the increased risk of internal bleeding.

Prof. Colin Baigent of the University of Oxford and his colleagues performed a review of studies documenting serious vascular events like heart attacks and strokes, and major bleeds in six trials involving 95,000 people at low to average risk, and 17,000 people at high risk.

Their findings appear in this week's issue of the medical journal The Lancet.

Among 10,000 people with heart disease, the British researchers found that low dose Aspirin will prevent as many as 200 strokes and heart attacks over one year.

But in 10,000 healthy people, low dose Aspirin will prevent seven strokes and heart attacks. Among healthy men and women, that modest benefit is cancelled out by an increased risk of internal bleeding, the researchers said.

Guidelines not justified
In the secondary prevention studies among people who had already had a stroke or heart attack and were at high risk for another, Aspirin reduced the risk of serious vascular events by about a fifth ? a benefit that clearly outweighed any small extra risk of bleeding. That finding backs current guidelines for Aspirin's use.

"The currently available trial results could well help inform personally appropriate judgments by individuals about their own use of long-term Aspirin, they do not seem to justify general guidelines advocating the routine use of Aspirin in all healthy individuals above a moderate level of risk for coronary heart disease," the study's authors concluded.

There is no good evidence that the benefits of long-term use of Aspirin exceed the risks by an appropriate margin for tens of millions of healthy men and women of all ages worldwide who could potentially be affected, Baigent said.

Health Canada and the U.S. Food and Drug Administration say Aspirin is indicated for primary prevention to reduce the risk of a first non-fatal heart attack in people deemed at risk by their physicians, which the packaging also suggests.

In a commentary accompanying the review, Prof. Ale Algra and Dr. Jacoba Greving of the University Medical Centre in Utrecht, Netherlands, agreed that in most cases, Aspirin is not justified for primary prevention.

"Patients might not wish to be medicalised ? such considerations are important in the decision to take Aspirin or not," the pair wrote.

They stressed the importance of making lifestyle changes such as quitting smoking, eating a healthy diet and getting regular exercise, in addition to considering drugs like Aspirin or cholesterol-lowering statins.