Aspirin primary prevention trial in Japan halted for lack of mortality benefit

Low-dose aspirin for primary prevention reduced nonfatal myocardial infarction, but not death from cardiovascular causes, in older Japanese patients, a recent study found.

The Japanese Primary Prevention Project randomized more than 14,000 patients, ages 60 to 85 years, with hypertension, dyslipidemia, or diabetes to 100 mg of enteric-coated aspirin per day or no aspirin. They were recruited from 1,007 primary care clinics between March 2005 and June 2007 and followed for up to 6.5 years. Study results were published online by the Journal of the American Medical Association on Nov. 17.

The primary outcome of the study was a composite of death from cardiovascular causes, nonfatal stroke, and nonfatal myocardial infarction, and the trial was terminated early due to lack of difference between groups on this outcome. At 5 years, the event rate was 2.77% in the aspirin group versus 2.96% in the non-aspirin group (hazard ratio [HR], 0.94; P=0.54). The aspirin group did have significantly lower risk of nonfatal myocardial infarction (HR, 0.53; P=0.02) and transient ischemic attack (HR, 0.57; P=0.04). The risk of extracranial hemorrhage requiring transfusion or hospitalization was higher in the aspirin group (HR, 1.85; P=0.004).

The researchers concluded that this dose of aspirin did not reduce the composite outcome in older Japanese adults with the specified risk factors. They noted that if the study had been continued until it was adequately powered, there was a 28% chance that aspirin would have shown a significant reduction in events. The study was limited by a lower rate of events in both groups than expected, as well as lack of adherence in the aspirin group (76% at 5 years) and use of aspirin in the control group (10% at 5 years), as well as loss to follow-up. Hemorrhagic stroke is more common in Japanese patients than Western ones, the study authors noted.

Although it was not effective for primary prevention, the use of aspirin may have offered study patients other benefits, such as prevention of cancer, the study authors said. The study authors plan to further analyze their data, including cancer deaths, to try to identify specific patient groups that may have benefited.

The results of this study are consistent with other primary prevention trials, according to an accompanying editorial. Aspirin is clearly indicated for high-risk patients, and not for low-risk ones, but the precise cutoff is still unknown, said the editorialists. Several trials that are currently underway should help refine guidelines on this topic and help clinicians decide when to recommend aspirin for primary prevention.