Aspirin: the quandary continues
Primary prevention of cardiovascular disease called into question
Aspirin has been around for thousands of years — known as a salicylate — but the form we are most accustomed to was discovered by a scientist named Felix Hoffmann, who worked for Bayer, in 1897 (1). Presently, there are over 100 billion tablets of aspirin consumed worldwide on annual basis (2). It is one of the most broadly accepted prophylactic medications. It has been used for a long time in primary prevention — those who are taking the medication to prevent the disease but don’t have it. Thus, you would think that we know all about aspirin, including its effectiveness as a prophylactic in different diseases and its side effects. However, this is far from reality.
In modern day, aspirin is used mainly for its antiplatelet effects, preventing clots and as an anti-inflammatory rather than for its antipyretic (fever) and analgesic (pain) benefits.
Is it beneficial, or is it oversold and dangerous? Every time we think we know the answer, another new study says the opposite. In other words, for every positive study, there are also negative studies about its side effects and complications.
Aspirin may play a role in a number of diseases, including cardiovascular disease (stroke and heart disease); multiple cancers, such as colorectal cancer and liver cancer; and age-related macular degeneration.
However, there are several risks with aspirin. The two most widely known side effects are gastrointestinal bleed and intracranial hemorrhage, or bleeding in the brain. Let’s look at the evidence.
Aspirin’s prophylactic role may be in question. We’re certain that aspirin works in primary prevention of cardiovascular disease, right? Why else would we put so many people, who were otherwise healthy, on aspirin? Not so fast. The Food and Drug Administration and recent studies indicate that aspirin may not be effective, or the evidence is inconclusive when comes to benefit outweighing risk.
Bayer AG, the pharmaceutical company, requested a change in the low-dose (baby aspirin or 81 mg.) aspirin label to include prevention of heart attacks. The company wanted to market the drug for those who were otherwise healthy but wanted to prevent a heart attack. The FDA, spurred by this requested change, stated on May 5 that the evidence for using aspirin in primary prevention of cardiovascular disease, including both heart attack and stroke, was not convincing or supportive enough to recommend the drug for this use (3). The FDA also said that the patients who wanted to use it for this indication should talk to their doctor about the risk-benefit ratio.
This response came as a surprise to many in the medical community considering that the American Heart Association, contrary to the FDA, supports aspirin use in in those who are at high risk for cardiovascular disease development. However, the agency did say that those who already have cardiovascular disease should be taking aspirin. But this is secondary prevention that the FDA supports, not primary. If you are already on aspirin for primary prevention, you should discuss it with your doctor before stopping the medication.
This is still a highly controversial issue, but it does not help that the FDA, one of the most respected institutions in medicine, weighed in on the topic to suggest that the risks may outweigh the benefits.
According to a study published in Lancet, the side effects may outweigh the benefits, as the FDA implied (4). Aspirin may also detract from the effectiveness of some cardiovascular risk-reducing classes of blood pressure lowering medications, such as angiotensin-converting enzymes inhibitors, like Lisinopril (5). Another study shows that aspirin is also associated with hearing loss (6).
There is also a suggestion that aspirin may increase the risk of macular degeneration. Let’s investigate this further.
Age-related macular degeneration
A recent observational study suggests that aspirin increases the risk of one type of advanced-stage macular degeneration by almost 2.5-fold in those who used aspirin on a chronic (weekly or more) basis (7). This type of macular degeneration is referred to as wet, or neovascular, AMD. However, there was not an increased risk in a second form of advanced AMD, geographic atrophy. This study followed 2,389 patients for 15 years.
Therefore, we should not use aspirin if patients have a high risk for AMD or have early stage AMD, right? Not necessarily. This study was flawed and difficult to apply to this country; it was done in Australia, and the dose most commonly used was assumed to be 150 mg., but the doses were not quantified. Aspirin does not come in this dose in this country. Also, patients were asked only at the start of the trial how frequently they used aspirin over the last year. Therefore, there was also recall bias.
In another study, aspirin did not show an association with an increased risk of AMD (8). I said it was complicated.
We have thought that aspirin may prevent the occurrence of colorectal cancer. There are some studies suggesting this is the case and others suggesting no effect. But there is a new wrinkle in this discussion. A recent study implies that your DNA may be an important factor to determining whether you will see a benefit from aspirin as a preventive of this cancer (9).
If your genes produce a large amount of an enzyme, 15-PGDH, then there is a significant 50 percent reduction in the risk of developing colorectal cancer in those whose use low-dose aspirin regularly, while those who produce low levels of the enzyme only see a 10 percent reduction in colorectal cancer with aspirin.
The reason is that aspirin and the enzyme both help control prostaglandins, which can be inflammatory. Together, the combination seems to have a profound effect on risk reduction. About half of the population produces significant amounts of the enzyme. You can test for this enzyme through colon biopsy during a routine colonoscopy. Therefore, targeted aspirin use may be the answer in colorectal cancer prevention.
Aspirin is obviously a tricky topic. At best, it prevents one in five cardiovascular events — stroke and heart attacks. This number comes from those who already have cardiovascular disease, and this may not be the case for primary prevention. Because aspirin has significant side effects, it is best not to depend on it for prevention in “healthy” individuals until there is solid data that it is an effective agent. However, it may make sense to prevent colorectal cancer in those who have complementary DNA, but we need larger, well-controlled trials confirm these results. As always, consult with your doctor before starting or stopping an aspirin regimen.
(1) Tex Heart Inst J. 2007;34:179-186. (2) Proc Natl Acad Sci USA. 2002;99:13371-13373. (3) fda.gov. (4) Lancet. 2009;374:878. (5) J Am Coll Cardiol. 2001;38:1950-1956. (6) Am J Med. 2010;123:231-237. (7) JAMA Intern Med. 2013;173:258-264. (8) PLoS ONE. 2013;8:e58821. (9) Sci Transl Med. 2014;6:233re2.
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Dr. Dunaief is a speaker, author and local lifestyle medicine physician focusing on the integration of medicine, nutrition, fitness and stress management. For further information, go to the website medicalcompassmd.com and/or consult your personal physician.