An Aspirin a Day - NOT the Best Way?

An Aspirin a Day - NOT the Best Way?

Aspirin is one of the oldest, most widely used drugs in history with records indicating that Hippocrates and Galen used the compound (in the form of willow tree bark) analgesic and anti-inflammatory properties.

These days the over-the-counter painkiller is used as an affordable prophylactic for cardiovascular-related events, with most major heart health organizations advocating for the use of aspirin daily.

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In fact, the American Heart Association (AHA) advises that individuals who have a high risk of heart attack take a low-dose of aspirin daily (if recommended by their respective doctors) as well as those individuals who are heart attack survivors. [1]

The reason aspirin is used in the prevention of cardiovascular events is due to its ability to suppress platelet aggregation without adversely impacting endothelial cell function. [2]

However, a new study published in the Journal of the American Medical Association (JAMA) suggests you might want to hold off on your one-a-day use of aspirin.

The Aspirin Study

Researchers from King’s College London conducted a meta-analysis were they collected, reviewed, and analyzed data from 13 studies including over 164,000 people in their fifties, sixties, and seventies.

To be considered for inclusion in the meta-analysis, previously published research had to meet the following seven criteria:

  • The study was a randomized clinical trial (RCT)
  • Subjects enrolled in the RCTs had no known pre-existing cardiovascular conditions or disease;
  • The study had to compare aspirin (at any dose) to a placebo or “no treatment”
  • The studies had to conduct a follow-up with subjects at least 12 months after the initial testing was completed
  • Each study had to include a minimum of 1000 test subjects
  • Each study must provide information on any of the pre-specified primary and secondary cardiovascular outcomes comes, primary and secondary bleeding outcomes, or cancer outcomes; and 
  • Must be available in the English language (Remember, these researchers are concerned with aspirin and heart health, not practicing their ability to translate foreign languages correctly)

Researchers filtered through more than 1300 articles to identify the 13 studies that satisfied the inclusion criteria set forth by the team.

So, what were they looking for?

The primary objective of the meta-analysis was to see what association (if any) there was between aspirin consumption and cardiovascular events as well as daily aspirin ingestion and bleeding events in individuals without cardiovascular disease.

Previous meta-analyses had been conducted investigating the relationship between daily low-dose aspirin and cardiovascular events. However, three new large-scale studies have been published in 2018.

Thus, the new meta-analysis by Zheng and colleagues sought to determine if these new findings had any sort of significant impact on previous findings.

And, in case you were wondering why there were three studies in 2018 investigating links between aspirin intake and reductions in cardiovascular events, the trials were conducted to fill gaps in the current body of literature, specifically involving patient groups who have not been well represented in previous trials.

Those three studies were: [5][6][7][8][9]

  • A Study of Cardiovascular Events in Diabetes (ASCEND) trial for patients with diabetes (included 15,480 subjects)
  • Aspirin for Reducing Events in the Elderly (ASPREE) trial for older patients (involved 19,114 subjects)
  • Aspirin to Reduce Risks of Initial Vascular Events (ARRIVE) trial for patients at higher CVD risk based on multiple risk factors (involved 12,546 subjects)

So, with these new studies added to the 10 previous large-scale interventions, what did the researchers learn regarding associations between aspirin and the heart?

The Findings

Researchers noted that aspirin use was associated with reductions in the following cardiovascular outcome:

  • cardiovascular mortality
  • nonfatal myocardial infarction
  • nonfatal stroke 

More specifically, researchers noted that individuals who consumed a once a day low-dose aspirin had approximately an 11% lower risk of cardiovascular events such as stroke, heart attack, or heart disease.

However, in line with previous research, researchers also noted that aspirin use was associated with an increased risk of bleeding (including intracranial and gastrointestinal).

To put the benefit/risk percentages identified in the study in real-world numbers and give them some context, Kevin McConway from the Open University in the UK, stated that based on this new information, when taking a daily aspirin “57 people rather than 61 people per 10,000 would be expected to suffer a heart attack or stroke; at the same time, 23 rather than 16 people per 10,000 would experience severe bleeding, on average.” [11]

Speaking on the team’s findings, lead researchers Sean Zheng BM, BCh, MA, MRCP stated:

“This study demonstrates that there is insufficient evidence to recommend routine aspirin use in the prevention of heart attacks, strokes and cardiovascular deaths in people without cardiovascular disease.” [10]

Following publication of the meta-analysis, JAMA also published an editorial, written by J. Michael Gaziano, MD MPH, in which he discusses the findings of the review and offers his take on the findings:

“The best estimates for the effects of aspirin on CVD events and bleeding have not materially changed after the results of the 2018 trials….

...When applying these results to an individual patient, clinicians must consider other interventions in addition to aspirin, such as smoking cessation and control of blood pressure and lipid levels, to lower risk. In places of the world in which CVD risk is rising or where other preventive strategies, such as statins, are less available, aspirin as a low-cost intervention may have a more important role.” [4]

Now, it should be noted that one of the big limitations of this new meta-analysis is that the studies analyzed used different doses of aspirin, ranging from 50-500mg. Typically though, doctors prescribe 80-100mg doses for the prevention of cardiovascular events. So, one has to consider the quality of the findings given the discrepancy in the doses used.

What Does This Mean for You?

The take-home message for those at risk for cardiovascular events is that taking a daily low-dose aspirin may offer a small measure of protection but there is also the possibility of internal bleeding.

As such, before self-medicating and popping aspirin on your own, consult with your physician to weigh the pros and cons of regularly taking aspirin and explore what other lifestyle changes can be made (diet, exercise, quitting smoking or alcohol, etc.) as well.

References

1) "Aspirin and Heart Disease." Www.heart.org, www.heart.org/en/health-topics/heart-attack/treatment-of-a-heart-attack/aspirin-and-heart-disease.

2) Dippel DW, Van Kooten F, Leebeek FW, van Vilet HH, Mehicevic A, Li SS, Koudstaal PJ. What is the lowest dose of aspirin for maximum suppression of in vivo thromboxane production after a transient ischemic attack or ischemic stroke? Cerebrovasc Dis 2004;17:296–302

3) Zheng SL, Roddick AJ. Association of Aspirin Use for Primary Prevention With Cardiovascular Events and Bleeding Events: A Systematic Review and Meta-analysis. JAMA. 2019;321(3):277–287. doi:10.1001/jama.2018.20578

4) Gaziano, J. M., & Greenland, P. (2014). When should aspirin be used for prevention of cardiovascular events? JAMA - Journal of the American Medical Association, 312(23), 2503–2504. https://doi.org/10.1001/jama.2014.16047

5) ASCEND Study Collaborative Group,Bowman L, Mafham M, et al. Effects of aspirin for primary prevention in persons with diabetes mellitus.N Engl J Med. 2018;379(16):1529-1539. doi:10.1056/ NEJMoa1804988

6) McNeil JJ, WolfeR, Woods RL, et al.Effect of aspirin on cardiovascular events and bleeding in the healthy elderly. N Engl J Med. 2018;379(16):1509- 1518.doi:10.1056/NEJMoa1805819

7) McNeil JJ, Nelson MR,Woods RL, et al. Effect of aspirin on all-cause mortality in the healthy elderly.N Engl J Med. 2018;379(16):1519-1528. doi:10.1056/ NEJMoa1803955

8) McNeil JJ, Woods RL, Nelson MR, et al. Effect of aspirin on disability-free survival in the healthy elderly. N Engl J Med. 2018;379(16):1499-1508. doi:10.1056/NEJMoa1800722

9) Gaziano JM, Brotons C, Coppolecchia R, et al. Use of aspirin to reduce risk of initial vascular events in patients at moderate risk of cardiovascular disease (ARRIVE): a randomised, double-blind,placebo-controlled trial.Lancet. 2018;392(10152):1036-1046. doi:10.1016/S0140- 6736(18)31924-X

10) Nield, David. "A Common Daily Medication Raises The Risk of Severe Internal Bleeding, Doctors Warn." ScienceAlert, www.sciencealert.com/study-shows-the-dangers-outweigh-the-benefits-when-it-comes-to-a-daily-aspirin.

11) "Large Meta-study Reveals Aspirin Bleeding Risks Outweigh Heart Benefits." New Atlas - New Technology & Science News, 23 Jan. 2019, newatlas.com/aspirin-bleeding-risk-danger-outweigh-heart-benefits/58161/.

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