Mar 19, 2013

By Trevor Shewfelt, Pharmacist at the Dauphin Clinic Pharmacy

I cant draw. No really, producing stick figures are a challenge for me. My mom is artistic. Her brother is artistic. My sister and I are not. My daughter Emily can draw. In fact in Emilys grade 5 report card her teacher suggested she try shading to add some depth to her artwork. Emily is told to add some shading and I cant draw a discernible happy face. It is fascinating when your kids get abilities you never, ever had.

Hippocrates must look at his metaphorical children in the same way. Hippocrates, the Greek healer who is known as the father of western medicine, wrote about powdered willow bark over 2500 years ago. White willow bark was used to treat pain and fever. The active ingredient in white willow bark is thought to be salicin. Salicin is eventually changed in our bodies to salicylic acid and that is the same substance ASA is changed into. ASA is now used to treat things Hippocrates would have never dreamed of.


A couple thousand years after Hippocrates, chemists identified the active ingredient in white willow bark as salicin. In the late 1800s chemists at the Germany company Bayer made a synthetic version of salicin. This eventually became ASA or acetylsalicylic acid. Bayer gave ASA the trade name Aspirin.


ASA does interesting things in the body. It affects the enzyme cyclooxygenase and this decreases the pro-inflammatory chemicals the prostaglandins. We think that decreasing these prostaglandins is what causes ASA to be able to decrease pain and inflammation. We think that the decrease of the prostaglandin E1 in the brain is what causes ASA to be able to decrease fever. ASA also affects platelets. Platelets help your blood to clot. ASA stops the cyclooxygenase enzyme in the platelet from forming thromboxane. This permanently disables the platelet from being able to clot for the life of the platelet which is 7 to 10 days.


Because of this increase in bleeding risk, ASA has fallen out of favor as a pain and fever fighter and taken on a new role. Low dose ASA is now used routinely to prevent heart attacks and strokes in certain patients. Researchers have found that when we give ASA at low doses, it doesnt bother the stomach as much, but still completely knocks out enough platelets to stop blood clots forming in dangerous places. If a blood clot forms in the brain, a part of the brain dies and that is a stroke. If a blood clot forms in a vessel feeding the heart muscle, a piece of the heart muscle dies and that is a heart attack.


The Heart and Stroke foundation of Canada says every 7 minutes someone in Canada dies of heart disease or stroke. If ASA prevents heart attacks and strokes and it is very inexpensive, why shouldnt we put all adults on it? Well it is a risk benefit thing. If someone is at a low risk for a heart attack or stroke, ASA only prevents a cardiovascular event once out of every 1000 people on ASA. The problem is the ASA will cause about the same number of serious bleeds in the stomach or the brain. The risk benefit calculation doesnt even change if the patient has just diabetes. Having just diabetes increases your risk of heart attack and stroke, but giving ASA to someone with just diabetes doesnt prevent enough cardiovascular events to outweigh the bleeding risk.


ASA really starts benefitting people when they have multiple risk factors for heart attack and stroke. Lets say the person was over 40, had diabetes, smoked, had high blood pressure, high cholesterol, and a family history of heart disease. This person is at a significantly higher risk of heart attack and stroke. Now ASA will prevent enough cardiovascular events to justify the bleeding risk. Where ASA really comes into its own is secondary prevention. That means someone has already had a cardiovascular event. People who have already had a heart attack, mini-stroke, by-pass, stent, a blood expanding a narrowed artery or stroke all are at much higher risk of having another clot causing damage. These people need to be on a blood thinner and ASA may be the one their doctor chooses.


Does daily, long term low dose ASA do other good things? Maybe. Researchers now think ASA may also help fight cancer. In the March 11, 2013 online version of Cancer, Tang et. al looked at the Womens Health Initiative study and showed women taking ASA had less chance of getting a skin cancer called melanoma. Thats good, but a previous study looked at the same Womens Health Initiative study and found ASA did not prevent colorectal cancer. In March 2012 issues of the Lancet and Lancet Oncology researchers led by Peter Rothwell and John Radcliffe looked at a bunch of ASA trials. In one meta-analysis they looked at 51 studies in which some people were put on ASA to prevent heart attacks and strokes and some werent. The ones who werent put on ASA got cancer more often. In another paper they looked at 5 big ASA trials to prevent heart attack and stroke. They were looking to see how cancer spread or metastasized. Again the people on the ASA had less cancer spread than those not on ASA. Although these papers are very interesting, they arent randomized, double blind placebo controlled trials. The patients they were looking at were actually heart patients, some of which happened to have cancer. Ideally we would like to see a large group of people without cancer half be given a sugar pill and half be give low dose ASA. Then after a number of years the researchers would check to see which group got cancer more often. Then we would like to see a trial in which a large number of people with cancer are half given a sugar pill and half given ASA and see in which group the cancer spreads the fastest. That way we would have a better idea if this ASA effect on cancer is real or not.


Hippocrates wouldnt recognize a medical world full of micro-surgeries, MRI machines and gene therapy. He would recognize ASA if you told him it came from white willow bark. But like a proud father, I think he would be amazed by the properties it now has and the new amazing properties it might be proven to have just over the horizon.








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