The question appeared on the Diagnostic Equity site, paraphrased with the approval of site proprietor Tamara Lobban-Jones: “I’ve heard that some people take a ‘ton of baby aspirin.’ My doc told me to take only one a day. Does taking multiple tablets help with clotting? What does taking one aspirin do to the blood, and what do labs look like for those who take it vs those who don’t?”
This answer was provided by Kathryn Golab, MLS, SH, DCLS. Dr. Golab wrote: “You should follow your doctor’s orders for how frequently to take your prescribed medications. Aspirin works by making ‘platelets less sticky’, so they don’t stick together as easily and form blood clots. Taking too much aspirin can cause bleeding complications. There aren’t a lot of laboratory tests to check to see how aspirin affects patients, but there are some tests to determine if a patient is a non-responder to aspirin.
Added by me (Geo): Two landmark studies, The Physician’s Health Study, 1982–1996, and the Women’s Health Study, 1990–2001, demonstrated that healthy people over 50 should take one 81 mg aspirin (baby aspirin) a day to reduce the risk of heart attack and stroke. This was termed “primary prevention.” Higher doses provided no additional benefit. Further, the 2002 Antiplatelet Trialists’ Collaboration was a meta-analysis of randomised trials of antiplatelet therapy for the prevention of death, myocardial infarction, and stroke in high-risk patients. BMJ 2002;324: 71-86 that documented a composite 32% decrease in death, myocardial infarction, or ischemic stroke in vascular patients on 75–150 mg aspirin daily. The high-risk patients were those with prior cardiovascular events. However, in 2018, Gaziano JM, Brotons C, Coppolecchia R, et al. reported “the 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;22;392:1036–104, showed that aspirin offered no protection for those without cardiac indications, questionable protection for those with risk factors, and that aspirin’s bleeding risk outweighs its protection.
A 2019 landmark meta-analysis, Mahmoud AN, Gad MM, Elgendy AY, Elgendy IY, Bavry AA. Efficacy and safety of aspirin for primary prevention of cardiovascular events: a meta-analysis and trial sequential analysis of randomized controlled trials. Eur Heart J. 2019;40(7):607–17. doi: 10.1093/eurheartj/ehy813. PMID: 30561620, available from your medical library, provides this abstract:
Aims: The role of aspirin in the primary prevention setting is continuously evolving. Recent randomized trials have challenged the role of aspirin in the primary prevention setting.
Methods and results: Electronic databases were searched for randomized trials that compared aspirin vs. placebo (or control) in subjects without established atherosclerotic disease. The primary efficacy outcome was all-cause mortality, while the primary safety outcome was major bleeding. Summary estimates were reported using a DerSimonian and Laird random effects model. A total of 11 trials with 157 248 subjects were included. At a mean follow-up of 6.6 years, aspirin was not associated with a lower incidence of all-cause mortality [risk ratio (RR) 0.98, 95% confidence interval (CI) 0.93-1.02; P = 0.30]; however, aspirin was associated with an increased incidence of major bleeding (RR 1.47, 95% CI 1.31-1.65; P < 0.0001) and intracranial haemorrhage (RR 1.33, 95% CI 1.13-1.58; P = 0.001). A similar effect on all-cause mortality and major bleeding was demonstrated in diabetic and high cardiovascular risk patients (i.e. 10-year risk >7.5%). Aspirin was associated with a lower incidence of myocardial infarction (RR 0.82, 95% CI 0.71-0.94; P = 0.006); however, this outcome was characterized by considerable heterogeneity (I2 = 67%), and this effect was no longer evident upon limiting the analysis to the more recent trials. Trial sequential analysis confirmed the lack of benefit of aspirin for all-cause mortality up to a relative risk reduction of 5%.
Conclusion: Among adults without established cardiovascular disease, aspirin was not associated with a reduction in the incidence of all-cause mortality; however, it was associated with an increased incidence of major bleeding. The routine use of aspirin for primary prevention needs to be reconsidered.
Current studies address the value of primary prevention aspirin in the reduction of colon cancer, the management of pre-eclampsia, and in individuals with no cardiovascular disease but with cardiovascular risk, such as diabetes mellitus, high cholesterol, and obesity. We await definitive conclusions. Many studies, beginning in the early 1990s, indicate that a certain percentage of aspirin-takers derive no advantage–these are “aspirin non-responders.” Except perhaps in non-responders, there is no advantage to daily dosages above 81 mg, and frequent aspirin usage at any dosage raises the risk of mucocutaneous bleeding such as gastrointestinal bleeds, menorrhagia, epistaxis, and skin bleeds called “purpura.”
Click here for a 2019 PowerPoint presentation describing aspirin’s history, antiplatelet mechanism as it suppresses cyclooxygenase (COX-1) function, and the history of aspirin’s primary prevention efficacy.
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