DrG's Medisense Feature Article
19041-Aspirin_For_Prevention
Aspirin
for All???
by Ann Gerhardt, MD
April 2019
Print Version
Bottom
Line at the Top: People
at increased risk for cardiovascular disease who have minimal risk of
excessive bleeding should take 81-100 mg of aspirin a day for
prevention. Follow the guidelines concerning risk in the last
paragraph of this article. Ignore sensational news drawing
medical conclusions if the study didn’t include people like
you.
Atherosclerosis is the major cause of cardiovascular disease, including
heart attacks and stroke. It is a chronic disease, in which
cholesterol oxidation and microscopic blood vessel damage cause
inflammation, thickening and clots in the artery
wall.
Platelets normally circulate in blood to keep us from bleeding to death
by forming clumps that initiate clotting. However, in
response to
arterial micro-trauma, clumping platelets add to the blood vessel wall
thickening that closes them off.
Aspirin has remarkable anti-inflammatory and anti-clotting
effects. It does this by inhibiting production of
certain
inflammatory factors, including thromboxane.
Thromboxane
made in platelets triggers clumping when it is time to clot.
Aspirin irreversibly blocks platelet thromboxane production, thereby
inactivating a platelet’s ability to clot for the lifetime of
the
platelet.
We know that low-dose aspirin reduces risk of atherosclerosis in
arteries throughout the body, but by inhibiting clotting, aspirin also
increases risks of large bruises and excessive bleeding even with minor
nosebleeds, gastritis or skin cuts. Still, low dose aspirin
(81-100 mg per day) is standard preventive treatment after a person has
had a stroke or heart attack, even in those with very healthy
lifestyles, because the risk of dying from bleeding is less than that
from cardiovascular events.
Current debate revolves around the issue of using aspirin to prevent a
FIRST cardiovascular event. A recent study’s
results were
published as three papers in the October 18, 2018 “New
England
Journal of Medicine” (NEJM)
1.
Researchers
compared 100 mg
daily aspirin to placebo in 19,114 predominantly white Australians and
Americans older than age 70 (age 65 for American Blacks and Hispanics)
who had no known cardiovascular disease, dementia, disability, bleeding
risk or chronic disease that might be fatal within 5 years.
Only
4% smoked and 10% were diabetic. Most had hypertension and/or
cholesterol problems, for which about one-third took
medication.
After 4.7 years the aspirin group experienced slightly less death,
dementia and disability, but at the expense of more major
bleeding. At 4 years, aspirin takers started to have fewer
cardiovascular events, but the difference didn’t reach
statistical significance, and benefit was completely offset by major
bleeding. The authors conclude that aspirin has no net
benefit in
“an apparently healthy older population.”
Unfortunately, some medical people freaked out after this study and
threw the baby out with the bath water. An editorial opined
that
“aspirin for primary prevention is
dead.”
People in all age groups and risk categories stopped taking their
aspirin. All because a single study found that
aspirin’s
benefit is offset by major bleeding in Caucasians who have made it to
age 70 without significant disease. How irritating.
Why
should we extrapolate results of a study about healthy elderly white
people to different racial groups and younger people who may not be so
healthy and may have significant, as-yet unrealized vascular disease
risk?
Diabetics are a special population in this regard. Their
platelets clump more easily than normal, and they have multiple other
cardiovascular disease risk factors. Cardiovascular events
afflict diabetics twice as often as non-diabetics in any given age
group, occurring at about the same rate as a non-diabetic who has
already had a heart attack or stroke. Because of this, the
American Diabetes Association (ADA) recommended in 1997 that all
diabetics who have at least one additional heart disease risk factor
take prophylactic low dose aspirin. Risk factors include
overweight, particularly around the mid-section, high blood pressure,
lipid abnormalities and smoking.
The ASCEND trial
2,
published in 2018, addressed the need for
aspirin in
diabetics who don’t necessarily have that second risk
factor. It included 15,480 diabetics older than 39 years who
had
not yet been diagnosed with cardiovascular disease and didn’t
necessarily have another risk factor, though many did. Half
took
100 mg aspirin and the other half took placebo. During an
average
7.4 years of follow-up, cardiovascular events occurred in 8.5% of those
who took aspirin, vs. 9.6% the placebo group. Major bleeding
events occurred in 0.9% more aspirin-takers, and overall there was no
difference in death rate between the groups.
ASCEND reaffirmed that aspirin prevents cardiovascular events in
diabetics with or without other risk factors but concluded that the
cardiovascular benefit was offset by major bleeding events.
Since
the numerical risks of cardiovascular benefit and major bleeding events
are similar, in my opinion the choice about aspirin becomes a matter of
which disease type the patient fears most.
Addressing people under age 70, the United States Preventative Services
Task Force (USPSTF) recommendations about aspirin use, published just
this month, does not universally pan preventive aspirin use
3.
Based on data from 11 randomized trials published between 1989 and
2014, the USPSTF recommends low-dose aspirin for 50 to 59 years old
adults whose 10-year cardiovascular risk, taking into account a variety
of risk factors, exceeds 10% and who are not at excess risk for
bleeding. Risk factors include diabetes, high blood pressure,
high cholesterol/lipid levels, tobacco use, obesity and family history
of cardiovascular disease. They concluded that people age
60-69
years with elevated cardiovascular risk are also likely to benefit from
aspirin therapy, but the magnitude of benefit may be less than that for
those in their fifties. About other age groups, they felt
“the current evidence is insufficient to assess the balance
of
benefits and harms of initiating aspirin use for the primary
prevention” in those younger than 50 and those older than 70
years.
References:
1) Patrono C, et al. Low-Dose
Aspirin for the
Prevention of Atherothrombosis. NEJM 2005.
353;22:2373-83.
Three studies with first author McNeil JJ, et al. Effect of
Aspirin on Disability-free Survival in the Healthy Elderly, Effect of
Aspirin on Cardiovascular Events and Bleeding in the healthy Elderly,
and Effect of Aspirin on All-Cause Mortality in the Healthy
Elderly. NEJM 2018. 379;16:1499-1528.
2) The ASCEND Study Collaborative Group.
Effects of
Aspirin for Primary Prevention in Persons with Diabetes
Mellitus.
NEJM 2018. 379;16:1529-1539.
3)
www.uspreventiveservicestaskforce.org/Page/Document/RecommendationStatementFinal/aspirin-to-prevent-cardiovascular-disease-and-cancer