An aspirin a day…Does that make sense?

William Simonson, PharmD, BCGP, FASCP
Oregon State University, USA

We all are familiar with the saying, “An apple a day keeps the doctor away” but we are more likely to take an aspirin (ASA) a day. Nearly 40% of US adults older than 50 years of age use aspirin for the primary prevention of cardiovascular disease (CVD) (prevention of first MI or stroke) or for secondary prevention of CVD (prevention of recurrence of MI or stroke).1 In this column I’ll look at the daily use of ASA and will summarize the most current thoughts and recommendations.

Daily ASA use has become a routine part of the drug regimen of many elderly, particularly in “at-risk” individuals including those with diabetes mellitus; however, research published over the last five years calls in question the use of ASA for primary prevention of cardiovascular problems such as stroke and MI.2

My selection of this topic was triggered by recent discussions I’ve had with various prescribers. I was struck by the apparent confidence they had in their respective recommendations and was also struck by the difference in their recommendations including daily ASA dosage or whether I should even take it at all.

Since drug therapy in the elderly is based primarily on a risk vs. benefit assessment I’ll first discuss the potential risk of daily ASA therapy.

As with any drug, ASA is not free of side-effects. The problems most commonly associated with ASA use include bleeding, primarily in the gastro-intestinal tract and in the brain in the form of intracranial bleeding. Both the frequency and severity of these problems increase with duration of ASA therapy and dose. There are a number of conditions and factors that can increase the risk of GI bleeds including history of GI ulcers or upper-GI pain, preexisting bleeding disorders, renal failure, severe liver disease and thrombocytopenia.2 Other problems that can increase the chance of both GI and intracerebral bleeding include use of anticoagulant drugs or non-steroidal anti-inflammatory drugs, uncontrolled hypertension, male gender and older age.2

A recently published 10-year study from England sheds more light on bleeding risks of ASA related to age of patient.3 Half of study participants were over age 75, and it was found that they faced an increased risk of serious and even fatal bleeding. One of the study authors was quoted as saying that antiplatelet drugs, such as ASA, prevented a fifth of recurrent heart attacks and strokes but also led to about 3000 excess-bleeding deaths annually in Britain alone with the majority of those being over age 75.4 The author further stated that the benefits of ASA for secondary prevention of recurrent heart attacks and strokes clearly outweighed the relatively small risk of bleeding but in those over age 75 the risk of serious bleeding is higher, although the risk of upper-GI bleeding can be cut by 70e90%by the concurrent use of proton pump inhibitors.

Now for the potential benefits of daily ASA. Most people think of ASA as a preventative for cardiovascular disease but let’s first look at an aspect of ASA that is less well known. There is considerable evidence that ASA reduces the risk of cancer including colo-rectal cancer (CRC). New research conducted at Oregon State University has found that the anti-cancer activity of ASA may be due to its effects on blood platelets rather than acting directly on cancer cells. It has been determined that platelets increase the level of an “oncoprotein” called c-MYC, which in turn, supports the growth of cancer cells and helps them spread throughout the body. The researchers found that in human cancers this compound is over-expressed which essentially means that the protein is over-produced. Since ASA inhibits platelets this reduces communication between platelets and tumor cells which, in turn, indirectly reduces tumor cell growth. The researchers pointed out that ASA’s anti-platelet effect is just as effective with low doses as it is with high doses. They also point out that the interaction between platelets and cancer cells occurs early in a tumor’s development which may mean that the routine use of ASA or other anti-platelet products might serve as a safe and efficacious way to prevent cancer in higher risk individuals.5

More specifically, a recently published study suggests a link between low-dose ASA and reduced risk for specific type of breast cancer and some other cancers.6 Aspirin reduces inflammation and is also a weak aromatase inhibitor. Interestingly, a number of medications used to treat hormone-receptor-positive breast cancer including Arimidex, Aromasin and Femara, are also aromatase inhibitors. This preliminary study found that women who take low-dose ASA (81 mg) three or more times per week have a 16% lower risk of developing any type of breast cancer and a 20% lower risk of hormone-receptor positive, HER2-negative breast cancer.

Numerous studies have evaluated the role of ASA in preventing CVD and various governmental agencies and professional associations have released often conflicting recommendations and guide-lines regarding its use in either primary or secondary prevention of myocardial infarction or stroke. The 2011 American Heart Association/American Stroke Association guidelines for the prevention of stroke in patients with stroke or transient ischemic attack (secondary prevention), state that a 15% relative risk reduction in vascular events (stroke, death, MI) has been documented for aspirin compared with placebo.7

In 2014 the United States Food and Drug Administration (FDA) reversed its position that daily aspirin can prevent the primary risk of heart attack and stroke.8 The FDA also stated that, “. there are serious risks associated with the use of aspirin, including increased risk of bleeding in the stomach and brain, in situations where the benefit of aspirin prevention has not been established.”

More recently, the United States Preventative Services Task Force (USPSTF) updated its previous recommendations and evaluated the use of ASA for the prevention of CVD and CRC. I encourage readers who are interested in more in-depth information on this topic to read this very well-written document.1

The report was based on an evaluation of a number of clinical studies and the USPSTF recommendations give considerable recognition to the importance of risk v. benefit considerations and importantly, the report recognizes that clinical decisions, such as whether ASA should be taken daily to prevent CVD and/or CRC, are complex with many important factors for clinicians and patients to consider. These decisions involve more than just the scientific evidence alone and should include individual patient preferences.

The report points out that the optimal dosage of ASA if taken daily is not known. Various studies have looked at different dosages but they state that a pragmatic approach consistent with the available scientific evidence is the administration of 81 mg of ASA by mouth once daily which is the most commonly prescribed dosage in the United States.1

The USPSTF report points out that the implementation of such a decision is contingent on four primary factors: risk for bleeding, preferences about taking aspirin, baseline CVD risk and patient age. For example, it may take 5 years or more of taking daily ASA for reduction in CVD risk to be observed but it may take 10e20 years or longer for reduction of CRC risk to be apparent. These two factors, plus the increased risk of ASA-related bleeding tend to decrease the apparent benefit in older patients, but if the patient has a strong belief in the value of ASA therapy, that may make such therapy more likely.

Recommendation: take 81 mg of ASA daily for primary prevention of CVD and CRC.
Adults age 60-69 years with
10% 10 year CVD risk. Recommendation: individualize to patient and concerns about risk v. benefit. Patients who are not at increased risk for bleeding, who have a life expectancy of 10 years and who are willing to take low dose ASA daily for at least 10 years are more likely to benefit from taking 81 mg ASA daily.

Adults younger than 50 years and 70 years or older: Current evidence is insufficient to assess the risk v benefit of daily ASA therapy. The report notes that they were unable to assess the balance of benefits and harms in these age groups and they further recommend that adults 70 years of age or older who are currently taking ASA should discuss with their clinician whether they should continue.

The USPSTF recommendations discussed above are the most recent recommendations regarding routine aspirin use. They are endorsed by the American Academy of Family Physicians.9 The American Heart Association currently makes the following recommendation, “People at high risk of heart attack should take a daily low-dose aspirin (if told by their healthcare provider) and that heart attack survivors regularly take low-dose aspirin.” The organization prudently points out that routine ASA therapy should not be started without first consulting a physician and they also point out that risks and benefits of ASA therapy vary for each person.10

I’d like to be able to provide the readers with a clear and definite recommendation for daily ASA but, as pointed out by researchers and professional societies and organizations, ASA should be individualized and used when benefits exceed potential risk. And, risk vs. benefit is what it’s all about in geriatric drug therapy.

References

1. Bibbins-Domingo K, on behalf of the U.S. Preventative Services Task Force. Aspirin use for the primary prevention of cardiovascular disease and colorectal cancer: US preventative services task force recommendation statement. Ann Inter Med;. http://dx.doi.org/10.7362/M16-0577. Accessed 4 August 2017.
2. Jennings D. New Guidelines for primary prevention of heart disease with aspirin. Pharm Times. Available at: http://www.pharmacytimes.com/contributor/douglas-jennings-pharmd-fccp-faha/2016/05/new-guidelines-for-primary-prevention-of-heart-disease-with-aspirin. Accessed 4 August 2017.
3. Li L, Geraghty OC, Mehta Z, et al, on behalf of the Oxford Vascular Study. Age-specific risks, severity, time course, and outcome of bleeding on long-term antiplatelet treatment after vascular Events: a population-based cohort study. Lancet. Published Online, https://doi.org/10.1016/S0140e6736(17)30770-5. Accessed 4 August 2017.
4. Hirschler B. Aspirin linked to higher risk of serious bleeding in the elderly. Geriatr Med. Available at: www.managedhealthcareconnect.com/content/aspirin-linked-higher-risk-serious-bleeding-elderly. Accessed 4 August 2017.
5. Sandolui A. New study explains how low dose aspirin may cause cancer. Med News Today. Available at: http://www.medicalnewstoday.com/articles/314889. php. Accessed 4 August 2017.
6. Clarke CA, Canchola AJ, Moy LM, et al. Regular and low-dose aspirin, other non-steroidal anti-inflammatory medications and prospective risk of HER2-defined breast cancer: the California Teachers Study. Breast Cancer Res. 2017;19:52. Available at: https://doi.org/10.1186/s13058-017-0840-7. Accessed 4 August 2017.
7. Lampert M. AHA/ASA guidelines on prevention of recurrent stroke. Am Fam Physician. 2011;83:993e1001. Available at: http://www.aafp.org/afp/2011/ 0415/p993.html. Accessed 4 August 2017.
8. FDA Finds Daily Aspirin Unnecessary for Heart Health. Daily Health Post. Avail-able at: https://dailyhealthpost.com/aspirin-side-effects/. Accessed 4 August 2017.
9. American Academy of Family Physicians, AAFP News. Evidence Backs Low-dose Aspirin for Ages 50-59, say USPTF, AAFP. Available at: http://www.aafp.org/news/health-of-the-public/20160413uspstfaspirin.html. Accessed 4 August 2017.
10. American Heart Association. Aspirin can help prevent heart attack. Available at: http://www.heart.org/HEARTORG/Conditions/HeartAttack/PreventionTreatment ofHeartAttack/Aspirin-and-Heart-Disease_UCM_321714_Article.jsp#.WYTkoNPyv Uo. Accessed August 4, 2017.