Low-Dose Aspirin Fails in Japanese Cardiac Study

A long term study in elderly Japanese patients indicates that long-term, low-dose daily use of aspirin did not result in a statistically significant improvement in cardiovascular outcomes, researchers reported in the online Journal of the American Medical Association.

The composite primary endpoint of cumulative cardiovascular events and death over 5 years was experienced by 2.77% of patients who took aspirin daily and by 2.96 patients who were not on aspirin therapy (P=0.54), reported Kazuyuki Shimada, MD, PhD, professor of medicine at Shin Oyama City Hospital, Tochigi, Japan.

Shimada reported that in the study of persons over the age of 60 in Japan "the clinical importance of aspirin in the primary prevention of cardiovascular events is less than originally anticipated in this patient population."

The researchers investigated a large number of secondary endpoints and determined that aspirin appears to significantly reduce the incidence of nonfatal heart attack – a 47% reduction compared with people not taking aspirin (P=0.02); and a 43% reduction in the incidence of transient ischemic attacks (P<0.044), Shimada said. However, that was somewhat offset by at 1.85-fold increase in serious extracranial hemorrhage (P=0.004).

The Japanese researchers enrolled 14,658 individuals into the study, assigning 791 people who were assigned to take one 100 mg enteric coated aspirin daily and 7335 individuals who were given placebo. The final analysis included 7220 people from the aspirin arm and 7244 from the placebo are, Shimada reported during a press conference at the American Heart Association where the paper was presented simultaneously with its online publication.

He said that in the modified intention-to-treat analysis the researchers observed 56 deaths in each arm. There were two fatal cerebral infarctions in the aspirin arm compared with seven fatal events in the placebo patients. There were five fatal intracranial hemorrhages in each arm. There were seven fatal myocardial infarctions in the aspirin arm compared with nine fatal heart attacks in the placebo arm of the study.

These patients in the study ranged in age from 60 years to 85 years of age. The majority of patients had hypertension, dyslipidemia or diabetes mellitus. They were recruited by primary care physicians at 1,007 clinics in Japan. The study was terminated early by the data monitoring committee after a median follow-up of 5.02 years based on likely futility – meaning it was unlikely that a result would show a statistically significant benefit of aspirin.

In an accompanying editorial in JAMA, J. Michael Gaziano, MD, professor of medicine at Brigham and Women's Hospital/ Harvard Medical School, and Philip Greenland, MD, professor of preventive medicine at Northwestern University Feinberg School of Medicine in Chicago, wrote that the findings from this study adds to the body of evidence that helps refine the answer to the question of when aspirin should be used to prevent vascular events.

"Decision making involves an assessment of individual risk-to-benefit that should be discussed between clinician and patient," they wrote. "However, at present the choice of aspirin remains clear in several situations. Aspirin is indicated for patients at high short-term risk due to an acute vascular event and those undergoing certain vascular procedures; patients with any evidence of vascular disease should be given daily aspirin. On the other hand, patients at very low risk of vascular events should not take aspirin for prevention of vascular events, even at low dose."

From the American Heart Association:

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