麻豆果冻传媒影音

CHICAGO -- Daily low-dose aspirin didn't reduce the elevated cardiovascular and stroke risk for older adults with diabetes, hypertension, or high cholesterol, according to a large Japanese trial.

The 5-year cumulative rate of death from cardiovascular causes, nonfatal stroke, or nonfatal myocardial infarction (MI) was 2.77% with 100-mg enteric-coated aspirin compared with 2.96% without it among such individuals ages 60 to 85 (P=0.54), reported , of Waseda University in Tokyo, and colleagues.

Aspirin did significantly cut down on nonfatal MIs by a relative 47% (5-year rate 0.30% versus 0.58%, P=0.02), and transient ischemic attack by a relative 43% (5-year rate 0.26% versus 0.49%, P=0.04).

However, the primary prevention strategy significantly increased extracranial hemorrhage requiring transfusion or hospitalization by a relative 85% compared with no aspirin (5-year rate 0.86% versus 0.51%, P=0.004), the group reported here at the American Heart Association meeting.

Their results from the open-label Japanese Primary Prevention Project also appeared online in the Journal of the American Medical Association.

An exploratory analysis suggested a 28% probability that the trial would have been positive if it had continued for the full planned number of events instead of being terminated early for futility after a median 5.02 years of follow-up.

"However, even if the result had become statistically significant through prolongation of the study, the clinical importance of aspirin in the primary prevention of cardiovascular events would have been less than originally assumed," Ikeda's group noted. "Therefore, it appears that aspirin is unlikely to show a clinically important benefit in the overall population included in this study."

Those results were largely consistent with those of prior primary prevention trials, which predominantly included very low-risk individuals, , of Brigham and Women's Hospital in Boston, and , of Northwestern University in Chicago, noted in an accompanying editorial.

Even as planned, the trial had only been powered to find a larger benefit (20%) than seen in pooled results of prior primary prevention trials (12%), the editorialists noted.

Further Research

Whether there is still some group, such as patients with multiple risk factors, that would benefit from aspirin primary prevention still remains an open question, Gaziano and Greenland suggested.

"It remains likely that there is some level of risk of cardiovascular disease events that would result in a positive tradeoff of benefit and risk for the use of aspirin, but the precise level of risk is uncertain," they wrote. "This is in part because most populations studied have been at very low risk."

Finding groups who would benefit should be pursued "with vigor" given how inexpensive aspirin would be as a prevention strategy, particularly for low-income countries, Dorairaj Prabhakaran, MD, director of the Centre for Non-Communicable Diseases of the Public Health Foundation of India, told reporters at a press conference.

Other aspirin primary prevention trials in above-average risk groups are underway in predominantly Western populations:

• ASCEND in patients ages 40 and older with type 1 or 2 diabetes
• ARRIVE in middle-age and older patients with multiple cardiovascular risk factors
• ASPREE in individuals over age 70

"Information from these studies will help refine guidelines that currently reserve aspirin for higher-risk patients," Gaziano and Greenland concluded. "Findings from these studies, with additional data about risks and other potential long-term benefits, such as reducing the risk of colorectal and other cancers, will prove helpful for clinical decision making involving the role of aspirin for primary prevention."

Aspirin could still be worthwhile prophylaxis for older adults given a growing body of evidence that it reduces risk of colorectal and other cancers, as well as cancer recurrence, the researchers agreed.

"Reduction in the incidence of colorectal cancer may influence the overall benefit-risk profile of aspirin," they wrote. "Further analyses of the Japanese Primary Prevention Project study data are planned, including analysis of deaths associated with cancers, to allow more precise identification of the patients for whom aspirin treatment may be most beneficial."

The Trial

The Japanese Primary Prevention Project included 14,464 people, ages 60 to 85, recruited by primary care physicians at 1,007 clinics in Japan as candidates for primary prevention due to hypertension, dyslipidemia, or diabetes.

They were randomized to open-label treatment with once-daily, enteric-coated aspirin at 100 mg or no aspirin.

Cardiovascular events were adjudicated by a multidisciplinary expert panel blinded to treatment assignment. As expected, gastrointestinal events were more common with aspirin.

Subgroup analyses by hypertension, dyslipidemia, diabetes, male sex, age 70 and older, overweight and obesity, smoking, and family history of premature cardiovascular disease didn't turn up significant impacts of aspirin either.

Adherence to aspirin was high initially and remained at 76% at 5 years. Aspirin and other antiplatelet or anticoagulant medication use in the group not assigned to aspirin was low at first but did climb to around 10% each by year 5.

"Although these issues present challenges for the conduct of long-term trials, they reflect the real practice of medicine in the 21st century," the editorialists noted.

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