The recent reports regarding President Trump’s swollen ankles and hand bruising mentioned that he is taking aspirin. His press secretary said, “This is consistent with minor soft tissue irritation from frequent handshaking and the use of aspirin, which is taken as part of a standard cardiovascular prevention regimen.”
This statement may have been true 10 years ago, but it is no longer. The use of low-dose aspirin is associated with an increased risk of bleeding that outweighs any protective effect it may have on coronary artery disease or thrombotic stroke. Surprisingly, the press has not picked up on this outdated and risky treatment.
VIP medicine is a risky business for the physician who is assigned such a task. The fear of missing something in a very prominent patient often leads to a surplus of diagnostic tests that carry more risk than benefit because of overdiagnosis and overtreatment. Also, this is an opinion based on experience but not hard data, the best physicians typically avoid taking on such a responsibility because they have other things to do and are aware of the problem inherent in caring for a high-visibility patient.
Below are two articles with pertinent references previously published here that deal with the use of aspirin in the primary prevention of heart disease and stroke. Primary prevention is designed to prevent an event that has not happened. This is in contrast to secondary prevention, which attempts to prevent a recurrence of something that has happened previously – ie, a second heart attack or stroke.
President Trump has not had a thrombotic stroke or a coronary event. Thus, his aspirin therapy is primary prevention. As shown below, this regimen carries more risk than gain.
Low-Dose Aspirin and the Risk of Stroke
Written by Neil Kurtzman | 26th July 2023
Low-Dose Aspirin and the Risk of Stroke and Intracerebral Bleeding in Healthy Older People – Secondary Analysis of a Randomized Clinical Trial is a study just published in the JAMA. It demonstrates another reason why low dose aspirin for the primary prevention of cardiovascular disease is harmful rather than therapeutic. The study found a significant increase in intracranial bleeding with daily low-dose aspirin but no significant reduction of ischemic stroke. Its abstract is below. Primary prevention is designed to prevent an event which has yet to occur – eg, a first stroke or heart attack. Secondary prevention is an attempt to prevent a recurrence of something that has already happened at least once.
The reason that aspirin may be useful in secondary prevention is that the risk of a stroke or heart attack in someone who has already had one is so much greater compared to an individual that has never had one of these that the risk:benefit ratio may be favorable for aspirin as a secondary preventative despite its propensity to cause bleeding.
Abstract
Importance Low-dose aspirin has been widely used for primary and secondary prevention of stroke. The balance between potential reduction of ischemic stroke events and increased intracranial bleeding has not been established in older individuals.
Objective To establish the risks of ischemic stroke and intracranial bleeding among healthy older people receiving daily low-dose aspirin.
Design, Setting, and Participants This secondary analysis of the Aspirin in Reducing Events in the Elderly (ASPREE) randomized, double-blind, placebo-controlled trial of daily low-dose aspirin was conducted among community-dwelling people living in Australia or the US. Participants were older adults free of symptomatic cardiovascular disease. Recruitment took place between 2010 and 2014, and participants were followed up for a median (IQR) of 4.7 (3.6-5.7) years. This analysis was completed from August 2021 to March 2023.
Interventions Daily 100-mg enteric-coated aspirin or matching placebo.
Main Outcomes and Measures Stroke and stroke etiology were predetermined secondary outcomes and are presented with a focus on prevention of initial stroke or intracranial bleeding event. Outcomes were assessed by review of medical records.
Results Among 19 114 older adults (10 782 females [56.4%]; median [IQR] age, 74 [71.6-77.7] years), 9525 individuals received aspirin and 9589 individuals received placebo. Aspirin did not produce a statistically significant reduction in the incidence of ischemic stroke (hazard ratio [HR], 0.89; 95% CI, 0.71-1.11). However, a statistically significant increase in intracranial bleeding was observed among individuals assigned to aspirin (108 individuals [1.1%]) compared with those receiving placebo (79 individuals [0.8%]; HR, 1.38; 95% CI, 1.03-1.84). This occurred by an increase in a combination of subdural, extradural, and subarachnoid bleeding with aspirin compared with placebo (59 individuals [0.6%] vs 41 individuals [0.4%]; HR, 1.45; 95% CI, 0.98-2.16). Hemorrhagic stroke was recorded in 49 individuals (0.5%) assigned to aspirin compared with 37 individuals (0.4%) in the placebo group (HR, 1.33; 95% CI, 0.87-2.04).
Conclusions and Relevance This study found a significant increase in intracranial bleeding with daily low-dose aspirin but no significant reduction of ischemic stroke. These findings may have particular relevance to older individuals prone to developing intracranial bleeding after head trauma.
Prophylactic Aspirin in Healthy Elderly Adults
Written by Neil Kurtzman | 22nd September 2018
Three studies, published online on Sept 16, 2018 by the New England Journal of Medicine, examine the effect of prophylactic aspirin in healthy elderly patients. The subjects received 100 mg of aspirin daily or a placebo for five years. Trial participants were community-dwelling men and women from Australia and the United States who were 70 years of age or older (or ≥65 years of age among blacks and Hispanics in the United States).
Effect of Aspirin on Disability-free Survival in the Healthy Elderly
Effect of Aspirin on Cardiovascular Events and Bleeding in the Healthy Elderly
Effect of Aspirin on All-Cause Mortality in the Healthy Elderly
Aspirin has been shown to reduce the recurrence of strokes and heart attacks in patients with cardiovascular disease – secondary prevention. Despite lack of persuasive evidence for the drug’s efficacy as a preventative for the development of a first stroke or heart attack (primary prevention) it has been widely used by subjects who do not have a medical indication for such use. The first paragraph of the first of these three papers by the same group of investigators gives the rationale for all three studies.
Several large, randomized trials have shown the efficacy of aspirin for the secondary prevention of cardiovascular disease among persons with a history of coronary heart disease or stroke.1-3 The evidence supporting a benefit of aspirin therapy in the primary prevention of cardiovascular or other chronic disease is less conclusive despite favorable trends suggesting that aspirin use reduces the incidence of cardiovascular events and possibly reduces the incidence of cancer and cancer-related mortality, particularly from colorectal cancer. Among elderly persons (more so than among younger persons), a higher risk of cardiovascular disease may increase the benefit of aspirin, but this benefit may be accompanied by an increased risk of bleeding. Despite the widespread use of low-dose aspirin in elderly persons who do not have a medical indication for aspirin, there is limited evidence that the beneficial effects outweigh the risks in this age group.
The three conclusion statements from these papers nicely sum up their findings:
Aspirin use in healthy elderly persons did not prolong disability-free survival over a period of 5 years but led to a higher rate of major hemorrhage than placebo.
The use of low-dose aspirin as a primary prevention strategy in older adults resulted in a significantly higher risk of major hemorrhage and did not result in a significantly lower risk of cardiovascular disease than placebo.
Higher all-cause mortality was observed among apparently healthy older adults who received daily aspirin than among those who received placebo and was attributed primarily to cancer-related death. In the context of previous studies, this result was unexpected and should be interpreted with caution.
The finding of higher cancer death rates was unexpected as earlier studies had suggested a beneficial effect of the drug on colon cancer. This reduction in the placebo treated group barely achieved statistical significance and likely has no clinical significance. But the lack of benefit of aspirin in the primary prevention of CVD is quite clear. Statin therapy is often employed to achieve primary prevention of CVD and also appears to lack the desired effect.
So what’s a worried person to do. The best advice is to live your life as best you can and face the fact that you’re mortal and that there’s a bullet out there that will inevitably find you. Most of my patients, virtually all, thought this recommendation to be far from what they wanted to hear. So here’s another. Keep your blood pressure below 140/90 – the recent guide of 130 systolic is, in my opinion, overkill. Aim for a BMI of about 25-30, but don’t be a fanatic about your weight – high or low. Treat comorbid conditions like diabetes. Take a walk every now and then. And most important – have the right parents.
What about younger subjects. Well, as mentioned above they’re less likely to develop CVD and thus aspirin is even less likely to be beneficial. Studies on younger people have uniformly showed no reduction in overall mortality from prophylactic aspirin treatment.
