I often encounter people who have taken baby aspirin for years because somebody once told them it was a good idea. In fact, low-dose aspirin is quite popular among healthy people for the purpose of reducing the risk of heart disease and stroke. Tens of millions of people in the United States take it daily to reduce their risk of heart attack or stroke. And numerous studies over the last two decades have suggested that taking aspirin on a regular basis may substantially the risk of developing or dying from cancer. (1). But, does everybody benefit from aspirin? Probably not. Then, who should take it and who should not? Aspirin is not without side effects. Therefore, it is important to weigh the benefits against the risk of adverse effects. The history of the drug may be traced back to ancient civilizations when patients were advised to chew on the bark of the willow tree to cure fever and relieve pain and inflammation. In 1828, Joseph Buchner, professor of pharmacy at Munich University, Germany managed to extract a substance he called salicin from willow. Salicin has powerful pain-relieving and anti-inflammatory effects. The active ingredient in Aspirin, acetylsalicylic acid, was synthesized for the first time in 1897 by a young chemist working for Bayer, Dr. Felix Hoffman (2). In 1899, acetylsalicylic acid was named Aspirin by Bayer. The letter ‘A’ stands for acetyl, “spir” is derived from the plant known as Spiraea ulmaria (meadowsweet), which yields salicin, and “in” was a common suffix used for drugs at the time of the first stable synthesis of acetylsalicylic acid (3). Thus, aspirin is one of the oldest and most commonly used drugs to relieve pain and cure fever. The first randomized study suggesting that a single daily dose of aspirin might reduce the risk of death among people with coronary heart disease was published in 1974 (4). Since then, many trials have studied the usefulness of the drug for disease prevention. Today, low-dose aspirin plays a key role in the treatment of cardiovascular disease (CVD), a common cause of death and disability worldwide. CVD includes coronary heart disease, cerebrovascular disease (vascular disease of the brain) and peripheral artery disease (arterial disease of the limbs). Low-dose aspirin is defined as 75-100 mg daily. A baby aspirin in the U.S. contains 81 mg of acetylsalicylic acid. This is much lower than the doses needed to relieve pain or reduce inflammation. How Does Low-Dose Aspirin Work? Platelets (thrombocytes) are small blood cells that are important in the formation of blood clots. One of their key functions is to stop bleeding. Aspirin interferes with the ability of platelets to aggregate or clump, thereby reducing clot formation. Platelets participate in the development and progression of atherosclerosis (5), the main underlying cause of cardiovascular disease. Furthermore, they are key components of blood clots that form on atherosclerotic plaques (thrombosis) and often severely limit blood flow to important organs such as the heart and the brain. Thrombosis is a term for blood clot occurring inside a blood vessel. Thromboxane A2 is a substance that plays a key role for the clumping of platelets and their blood clotting activity. The best-characterized mechanism behind the effects of low-dose aspirin is its inactivation of an important platelet protein called cyclooxygenase-1 or (COX-1)(6). The inactivation of COX-1 leads to a long-lasting suppression of thromboxane A2, thereby suppressing platelet activation and aggregation (7). Higher doses of the drug also inhibit COX-2, which blocks prostaglandin production leading to the drugs’ effect on pain, inflammation, and fever. The effects of the drug on platelet function explains its effectiveness in preventing thrombosis as well as its bleeding liability. tyle=”color: #993300;”>Aspirin for Patients with Cardiovascular Disease (Secondary Prevention) Among patients with established CVD, such as history of stroke or heart attack, both individual studies and meta-analyses of randomized trials indicate that low-dose aspirin reduces the risk of a new cardiovascular event (heart attack, stroke or death from vascular causes) by approximately 25 percent (8). The positive effect of the drug in secondary prevention is to a certain extent offset by an increased risk of bleedings from the gastrointestinal tract and an increased risk of brain hemorrhage. However, the risk/benefit ratio is clearly in favor of aspirin treatment. Consequently, all patients with established CVD should be offered daily treatment unless there is an excessive risk of bleeding. Aspirin for Healthy People (Primary Prevention) It has been suggested that aspirin may reduce the risk of CVD and some types of cancer among healthy people. Aspirin in Primary Prevention of Cardiovascular Disease Among people without a history of CVD (primary prevention), the risk reduction associated with treatment is much smaller than among those with a history of a vascular event. Several large meta-analyses have addressed the effects the drug for primary prevention (9,10). Taken together the results of these trials suggest that such treatment leads to a 20 percent relative reduction in the risk of heart attack (myocardial infarction), no significant effect on the risk of stroke, no significant effect on the risk of death from cardiovascular disease, and a 54 percent relative increase in the relative risk of bleedings, mostly from the gastrointestinal tract. There are several ongoing trials addressing the question whether people at increased risk, such as those with diabetes, may benefit from low-dose aspirin. Based on the currently available date, the risk/benefit profile of low-dose aspirin does not support such treatment for people without a history of CVD. The ratio of benefit to risk is much lower than in people with established CVD. Therefore, inappropriate over-prescription of the drug for primary prevention should be avoided. For some individuals age 50 years or greater without underlying CVD and without excess bleeding risks, the benefits of treatment for the prevention of cancer and CVD may outweigh the risks (11). The evidence does not support the routine use of the drug for primary prevention in patients younger than 50 years. Aspirin for Prevention of Cancer There is evidence that low-dose aspirin used over prolonged periods may reduce the risk of several types of cancer (12). The strongest evidence for this effect relates to of cancer of the colon and rectum (13). Randomized studies on the effect of the drug on the primary and secondary prevention of CVD have indicated that long-term treatment is associated with a reduction in cancer-related mortality. This may be explained by an effect on cancer prevention as well as a decrease in the spreading of cancers (metastasis)(14). Aspirin and Mortality As low-dose aspirin appears to reduce the risk of coronary heart disease and some cancers at the same time as it increases the risk of bleeding, it might be prudent to ask if aspirin treatment prolongs life. The effect on total mortality has been addressed in at least three meta-analyses (8,15,16). All these studies suggest that low-dose aspirin leads to a 6-8 percent relative reduction in total mortality. However, this effect is not clearly statistically significant suggesting that we can not be completely sure that there is an effect on all-cause mortlity. Adverse Effects of Aspirin The most common side effect of treatment is bleeding, most commonly from the gastrointestinal tract. Bleedings may also occur at other sites, with intracranial bleeding (brain hemorrhage) being the most serious. Several factors that may increase the risk of gastrointestinal bleeding associated with regular intake of the drug have been defined (17). These are: a history of peptic ulcer disease or gastrointestinal bleeding, older age, concomitant use of non-steroidal anti-inflammatory drugs (NSAID’s), concomitant use of other blood-thinning drugs, the presence of other underlying disease (e.g. diabetes, hypertension), and high aspirin dose. Sometimes, so-called proton pump inhibitors (PPI) are used to prevent drug-induced gastrointestinal bleeding. PPI’s are drugs used for the treatment of peptic ulcer disease. However, such treatment is not considered cost-effective for people with a low or average bleeding risk (18) which includes most people using aspirin for the purpose of primary prevention. Some people do not tolerate the drug because of hypersensitivity, usually manifested as respiratory symptoms such as rhinitis (inflammation of the mucous membranes of the inside of the nose) and asthma. More severe symptoms have been described but are rare. The Take Home Message Long-term treatment with low-dose aspirin appears to reduce the risk of cardiovascular events and some types of cancer. Evidence suggests that patients with an established cardiovascular disease, such as a history of heart attack or stroke, benefit from low-dose aspirin. In patients without a history of cardiovascular disease, the benefit/risk profile does not support routine treatment with low-dose aspirin. In this group of people, inappropriate over-prescription should be avoided. For some individuals age 50 years or greater without underlying cardiovascular disease and without excess bleeding risks, benefits of low-dose aspirin may outweigh the risks. Bleeding, most commonly from the gastrointestinal tract, is the most common adverse effect of treatment. Studies are under way to address the question whether specific subgroups, such as people with diabetes or elderly people, will benefit from low-dose aspirin. Source
