Conference Coverage
CHICAGO– Daily low-dose aspirin did not prevent atherosclerotic events in high-risk, elderly Japanese patients in the Japanese Primary Prevention Project.
After a median follow-up of 5 years, the composite primary outcome of cardiovascular death, nonfatal stroke, and nonfatal myocardial infarction occurred in 2.77% of patients with hypertension, dyslipidemia, or diabetes on aspirin and 2.96% of those not on aspirin, a nonsignificant difference.
Dr. Kazuyuki Shimada
Subgroup analyses did not identify significant differences between study groups, Dr. Kazuyuki Shimada reported at the American Heart Association scientific sessions.The study was stopped prematurely because the number of primary events was insufficient for the study to reach statistical power.
Daily low-dose aspirin, compared with no aspirin, however, significantly reduced the rate of nonfatal myocardial infarction (0.30% vs. 0.58%; HR, 0.53; P = .02) and transient ischemic attack (0.26% vs. 0.49%; HR, 0.57; P = .04).
However, these benefits must be weighed against an 85% increased risk of serious extracranial hemorrhage in patients on daily aspirin (0.86% vs. 0.51%; HR, 1.85, P = .004), Dr. Shimada of Shin-Oyama City Hospital, Tochigi, Japan, said.
Prespecified gastrointestinal adverse events, including stomach/abdominal pain, gastroduodenal ulcer, reflux esophagitis, and gastrointestinal hemorrhage, were also increased in patients on aspirin, according to results of the late-breaking study, simultaneously published online in JAMA ( doi:10.1001/jama.2014.15690).
Dr. Dorairaj Prabhakaran
Invited discussant Dr. Dorairaj Prabhakaran of the Public Health Foundation of India in Delhi said the negative results do not spell the “end of the road” for aspirin in primary prevention, but emphasize the need to use an individualized, stepwise risk-benefit approach to aspirin therapy.
“The benefit is very unlikely in very low-risk populations such as those with less than 1% [cardiovascular] events per year,” he said. “There would be a role in special groups such as younger populations, lower-income countries, but these are not evaluated well.”
During the discussion following the study presentation, panelists raised concerns about the development of polypills, most of which are for secondary prevention but typically contain aspirin. Other panelists said the study provides a sobering reminder of the risks faced by patients who put themselves on a daily aspirin regimen without consulting a physician.
The Japanese Primary Prevention Project ( JPPP) evenly randomized 14,658 patients, aged at least 60 years, with hypertension, dyslipidemia, or diabetes to enteric aspirin 100 mg or no aspirin. A total of 194 patients were excluded because of protocol violations, study withdrawal, or failing to meet inclusion criteria, leaving 7,220 patients in the aspirin group and 7,244 in the no-aspirin group for the modified intention-to-treat population.
In addition to the lower-than-expected total event rate in both the aspirin and no-aspirin groups (193 vs. 207), the use of statins in both arms could have contributed to the negative results, Dr. Shimada reported. Aspirin adherence also fell from 89% in year 1 to only 76% in year 5, while aspirin use in the no-aspirin group increased from 1.5% to 9.8%.
Further analyses are planned to determine whether aspirin is beneficial in select subgroups or in the prevention of cancer.
Dr. J. Michael Gaziano of Brigham and Women’s Hospital in Boston commented in an accompanying JAMA editorial ( doi:10.1001/jama.2014.16047) that information from three ongoing primary prevention aspirin trials in patients at higher-than-average risk “will prove helpful for clinical decision making involving the role of aspirin for primary prevention.”
Those trials include the ASCEND study of aspirin 100 mg with or without omega-3 fatty acids in patients at least 40 years old with diabetes, the ARRIVE trial in middle-aged and older patients at moderate risk of cardiovascular disease, and the ASPREE study in the elderly older than 65 years.
JPPP was sponsored by the Japanese Ministry of Health, Labor, and Welfare, and the Waksman Foundation of Japan. Bayer Yakuhin provided the aspirin. Dr. Shimada reported honorarium from MSD, Shionogi, Takeda, Daiichi-Sankyo, and Dainihon-Sumitomo, and serving as a consultant/advisory board member for Omron. Dr. Prabhakaran reported no relevant financial disclosures. Dr. Gaziano reported serving on the executive committee of the ARRIVE trial and as a consultant for and receiving speaking honoraria from Bayer.