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Aspirin: Should I Take it to Prevent a First Heart Attack or Stroke?

Aspirin: Should I Take it to Prevent a First Heart Attack or Stroke?

The benefits of taking aspirin for secondary prevention (e.g. in those who suffered a prior heart attack, stroke or those with coronary stents implanted) are beyond doubt. There is very robust data showing that aspirin in such patients reduces the future risk of major adverse cardiovascular events such as heart attacks and strokes.

However, the benefit of taking an aspirin a day for primary prevention (i.e. for the prevention of future heart attacks or strokes in otherwise healthy people ± cardiovascular risk factors) is controversial.

 

Aspirin

The term aspirin was coined in 1899 by Bayer, a German pharmaceutical company, where “a” stands for acetyl, “spir” is derived from the plant Spiraea ulmaria (meadowsweet), which yields salicin and “in” which was a common suffix used for drugs at the time.

 

New studies from 2018/2019: ARRIVE, ASCEND and ASPREE

Recently, 3 large randomized controlled trials – ARRIVE, ASCEND and ASPREE – evaluated the safety and efficacy of aspirin for primary prevention in high-risk, diabetic and elderly patients, respectively.

All 3 studies were published in the New England Journal of Medicine in 2018 (ARRIVE and ASCEND) and 2019 (ASPREE).

In the ARRIVE trial about 12,000 nondiabetic patients were randomized to 100mg of aspirin daily or to a placebo. Enrolled male patients were 55 or older and had ≥2 risk factors for heart disease. Enrolled women were 60 years or older and had ≥3 risk factors for heart disease. During an average follow-up of 5 years, aspirin therapy conferred no benefit. The incidence of the composite endpoint, which included heart attack and stroke, was about 4% in both groups. However, bleeding from the gastrointestinal tract, although rare, was twice as common among patients taking aspirin (1% vs 0.5%, p=0.0007).

In the ASCEND trial 15,000 middle aged or older patients with diabetes mellitus were randomized to daily aspirin (100mg) or placebo. After about 7 years of follow-up , the incidence of serious vascular events was 1% lower in the aspirin group than in the placebo group (8.5% vs 9.6%, p=0.01), but the incidence of major bleeding events was 1% higher with aspirin (4.1% vs 3.2%, p=0.003).

In the ASPREE trial researchers examined preventative aspirin therapy in the healthy elderly living in the community in the US and Australia. Age was the main criterion for study entry (≥70 years for whites; ≥65 years for blacks and Hispanics). Most study participants had 1 or 2 risk factors for heart disease but patients with established heart disease, substantial cognitive or physical disability or high risk for bleeding were excluded. However, most study participants had one or more cardiovascular risk factors.

About 19,000 patients (median age 74 years) were randomized to receive aspirin (100mg) or placebo daily. After 4.7 years of follow-up, the following outcomes were observed:

 

  1. No difference in the primary outcome (death, dementia or persistent physical disability) between both groups (10% in each group).
  2. All-cause mortality was slightly higher with aspirin than placebo (5.9% versus 5.2%). The difference was due to more cancer deaths in the aspirin group (3.1% vs 2.3%).
  3. No subgroup (including patients with multiple cardiovascular risk factors) derived cardiovascular benefit from aspirin.
  4. Major bleeding occurred slightly more frequently with aspirin than with placebo (3.8% vs 2.8%).

 

Meta-analysis

In early January 2019, a meta-analysis was published in the Journal of the American Medical Association (JAMA), which included data from 13 trials and 164,665 patients (including data from ARRIVE, ASCEND and ASPREE).

The median age of the trial participants was 62 years (range 53-74), 47% were men, 19% had diabetes and the median baseline risk for the primary cardiovascular outcome (cardiovascular mortality, nonfatal myocardial infarction and nonfatal stroke) was 9.2% (range 2.6% to 15.9%) (i.e. low to intermediate risk).

This study found that aspirin did reduce cardiovascular events by a modest 11%. The number needed to treat to prevent one event was 265, but aspirin also increased major bleeding, such as serious gastrointestinal bleeding, intracranial bleeding or bleeding requiring hospitalisation or blood transfusion by 43%. This number needed to harm was 210.

Therefore aspirin did reduce cardiovascular events but increased bleeding events to a similar magnitude, meaning that there was no net benefit.

 

Take home message

What do these results mean for patients taking aspirin for primary prevention?

There appears to be no net benefit to taking an aspirin a day for primary prevention and therefore I would be hesitant in prescribing aspirin for primary prevention. I would probably recommend a statin instead if the patient had a good indication for it (to be discussed in the next blog).

 

Author: Dr Crochan O’Sullivan MD, PhD, FESC, Consultant Cardiologist, Bon Secours Hospital, Cork.