High Risk of Major Bleeding from Low-Dose Aspirin Found by New Study
Study looked at those with and without diabetes in large study; aspirin appears to not increase risk for diabetics but non
5, 2012 - Just when new studies were beginning to solidify aspirin’s position as the wonder drug, for senior citizens in particular, the
bubble of optimism is burst by news that daily use of even low-dose aspirin may increase the risk of major bleeding in the stomach, intestines
or skull by more than 50 percent.
The large study of nearly 200,000 individuals also found that patients with diabetes had a high rate of such major
bleeding whether they took aspirin daily or not. It will be published tomorrow in the Journal of the American Medical Association (JAMA).
"Aspirin is not effective in protecting a person from a first cardiac event - a heart
attack or stroke," study author Dr. Antonio Nicolucci, head of the department of clinical pharmacology at
nonprofit biomedical research organization Consorzio Mario Negri Sud in Santa Maria Imbaro, Italy, told
"In addition, taking aspirin has significant risks, and thus shouldn't be part of primary
prevention unless you're at moderate to high risk of heart disease."
The U.S. Preventive Services Task Force in 2009
“found good evidence that aspirin decreases the incidence of myocardial infarction in men and ischemic strokes in women.”
The USPSTF also found, however, “good evidence
that aspirin increases the incidence of gastrointestinal bleeding and fair evidence that aspirin increases the incidence of hemorrhagic
It issued recommendations then (2009) for the
use of aspirin only in certain older people when the disease risk was greater than the potential damage caused by the aspirin.
(See summary recommendation of USPSTF
below this news report.)
The researchers knew that aspirin had earlier been associated with gastrointestinal and intracranial bleeding
complications. And, they were concerned that low-dose aspirin is recommended for certain patients with diabetes.
Low-dose aspirin is often used in the treatment of cardiovascular disease as a preventive therapy for those at high risk
of cardiovascular event, such as, those with multiple risk factors like hypertension, dyslipidemia, obesity, diabetes, and family history of
ischemic heart disease.
In addition, low-dose aspirin use is recommended for certain patients with diabetes. Findings from earlier meta-analysis
suggested that diabetes may increase the risk of extracranial hemorrhage.
“These estimates were derived from a limited number of events within randomized trials,’ the researches write. Hence, the
risk-to-benefit ratio for the use of low-dose aspirin in the diabetes patients was unclear.
“Any benefit of low-dose aspirin might be offset by the risk of major bleeding. It is known that aspirin is associated
with gastrointestinal and intracranial hemorrhagic complications. However, randomized controlled trials have shown that these risks are
The authors add that randomized controlled trials evaluate selected patient groups and do not necessarily generalize to
an entire population.
Results of this study
Giorgia De Berardis, M.Sc., of Consorzio Mario Negri Sud, Santa Maria Imbaro, Italy, and colleagues conducted the study
to determine the incidence of major gastrointestinal and intracranial bleeding episodes in individuals with and without diabetes taking
For the study, the researchers used administrative data from 4.1 million citizens in 12 local health authorities in
Individuals with new prescriptions for low-dose aspirin (300 mg or less) were identified during the index period from
January 2003 to December 2008, and were matched with individuals who did not take aspirin during this period.
The researchers included 186,425 individuals being treated with low-dose aspirin and 186,425 matched controls without
During 6 years, 6,907 first episodes of major bleeding requiring hospitalization were registered, of which there were
4,487 episodes of gastrointestinal bleeding and 2,464 episodes of intracranial hemorrhage.
Their analysis indicated that the use of aspirin was associated with a 55 percent increased relative risk of
gastrointestinal bleeding and 54 percent increased relative risk of intracranial bleeding.
The authors note that in comparison with other estimates of rates of major bleeding, their findings indicate a 5-times
higher incidence of major bleeding leading to hospitalization among both aspirin users and those without aspirin use.
Regarding the use of aspirin being associated with a 55 percent relative risk increase in major bleeding, “this
translates to 2 excess cases for 1,000 patients treated per year. In other words, the excess number of major bleeding events associated with
the use of aspirin is of the same magnitude of the number of major cardiovascular events avoided in the primary prevention setting for
individuals with a 10-year risk of between 10 percent and 20 percent,” they write.
Aspirin use among diabetes patients
The researchers also found that the use of aspirin was associated with a greater risk of major bleeding in most of the
subgroups evaluated, but not in individuals with diabetes.
Diabetes was independently associated with a 36 percent increased relative risk of major bleeding episodes, irrespective
of aspirin use. Among individuals not taking aspirin, those with diabetes had an increased relative risks of 59 percent for gastrointestinal
bleeding and 64 percent for intracranial bleeding.
“Our study shows, for the first time, to our knowledge, that aspirin therapy only marginally increases the risk of
bleeding in individuals with diabetes,” the authors write. “These results can represent indirect evidence that the efficacy of aspirin in
suppressing platelet function is reduced in this population.”
“In conclusion, weighing the benefits of aspirin therapy against the potential harms is of particular relevance in the
primary prevention setting, in which benefits seem to be lower than expected based on results in high-risk populations.
“In this population-based cohort, aspirin use was significantly associated with an increased risk of major bleeding, but
this association was not observed for patients with diabetes. In this respect, diabetes might represent a different population in terms of
both expected benefits and risks associated with antiplatelet therapy.”
The study did find a lower risk of stomach, intestine and skull bleeding associated with statins.
Editorial: Hemorrhagic Complications Associated With Aspirin – An
Underestimated Hazard in Clinical Practice?
“A decision-making process based on balancing an individual patient’s risk of bleeding and ischemic events is
difficult,” concludes Jolanta M. Siller-Matula, M.D., Ph.D., of the Medical University of Vienna, Austria, commenting on the findings of this
The study, she says in an editorial, “…underscores that the potential risk of bleeding should be carefully considered in
decision making. Assessment of bleeding risk and of net clinical benefit will merit further emphasis as issues inherent to aspirin use also
apply to more potent platelet inhibitors and anticoagulants; there is only a thin line between efficacy and safety, and the reduction in
ischemic events comes at the cost of increased major bleedings.
“Therefore, future studies investigating the risks and benefits for individual patients app ear to be mandatory to help
physicians appropriately make recommendations about aspirin use for primary prevention.”
Aspirin for the Prevention of Cardiovascular Disease
U.S. Preventive Services Task Force (USPSTF) Recommendations
Release Date: March 2009
This summarizes the U.S. Preventive Services Task Force (USPSTF) recommendations on aspirin for the prevention of
Summary of Recommendations
● The USPSTF recommends the use of aspirin for men age 45 to 79 years when the potential
benefit due to a reduction in myocardial infarctions outweighs the potential harm
due to an increase in gastrointestinal hemorrhage. Grade:
● The USPSTF recommends the
use of aspirin for women age 55 to 79 years when the potential benefit of a reduction in ischemic strokes outweighs the potential harm of an
increase in gastrointestinal hemorrhage. Grade:
● The USPSTF concludes that
the current evidence is insufficient to assess the balance of benefits and harms of aspirin for cardiovascular disease prevention in men and
women 80 years or older. Grade:
● The USPSTF recommends
against the use of aspirin for stroke prevention in women younger than 55 years and for myocardial infarction prevention in men younger than
45 years. Grade: