Low-Dose Aspirin for Primary Prevention of Cardiovascular Events in Japanese Patients 60 Years or Older With Atherosclerotic Risk Factors: A Randomized Clinical Trial | Journal Scan

Study Questions:

Does daily low-dose aspirin reduce the incidence of cardiovascular events in older Japanese patients with multiple atherosclerotic cardiovascular risk factors (CVRFs)?

Methods:

The JPPP (Japanese Primary Prevention Project) was a multicenter, open-label, randomized, parallel-group trial. Patients (n = 14,464) ages 60-85 years with hypertension, dyslipidemia, or diabetes mellitus were recruited by primary care physicians at 1,007 clinics in Japan between March 2005 and June 2007, and were followed up for up to 6.5 years. An expert panel adjudicated study outcomes. Patients were randomized 1:1 to enteric-coated aspirin 100 mg/d or no aspirin in addition to ongoing medications.

Results:

The study was terminated early by the data monitoring committee after a median follow-up of 5.02 years (interquartile range, 4.55-5.33) based on likely futility. In both the aspirin and no aspirin groups, 56 fatal events occurred. The 5-year cumulative primary outcome event rate was not significantly different between the groups (2.77% [95% confidence interval (CI), 2.40%-3.20%] for aspirin vs. 2.96% [95% CI, 2.58%-3.40%] for no aspirin; hazard ratio [HR], 0.94 [95% CI, 0.77-1.15]; p = 0.54). Aspirin significantly reduced incidence of nonfatal myocardial infarction (0.30 [95% CI, 0.19-0.47] for aspirin vs. 0.58 [95% CI, 0.42-0.81] for no aspirin; HR, 0.53 [95% CI, 0.31-0.91]; p = 0.02) and transient ischemic attack (0.26 [95% CI,0.16-0.42] for aspirin vs. 0.49 [95% CI,0.35-0.69] for no aspirin; HR, 0.57 [95% CI, 0.32-0.99]; p = 0.04), and significantly increased the risk of extracranial hemorrhage requiring transfusion or hospitalization (0.86 [95% CI, 0.67-1.11] for aspirin vs. 0.51 [95% CI,0.37-0.72] for no aspirin; HR, 1.85 [95% CI, 1.22-2.81]; p = 0.004).

Conclusions:

Once-daily, low-dose aspirin did not significantly reduce the risk of the composite outcome of cardiovascular death, nonfatal stroke, and nonfatal myocardial infarction among Japanese patients 60 years or older with atherosclerotic risk factors.

Perspective:

The implications of this open-labeled study of aspirin in elderly Japanese patients may not apply to European and US populations. The 5-year CV event rate was about 2.8% in this study. Using the Pooled Cohort and mean risk factor values in this study, the 10-year atherosclerotic cardiovascular disease rate would be 20%. Aspirin was not effective in previous Japanese studies in high-risk cohorts including diabetes and peripheral vascular disease. Several placebo-controlled trials of aspirin are ongoing in the United States including men and women at moderate risk (men ≥55 years and two or more CVRFs and women ≥60 years and three or more CVRFs), diabetes, and the elderly, each of which is enrolling about 12,000 subjects. Several years ago, the Australians concluded it would take at least 50,000 participants to determine the value of aspirin in a community sample of the elderly. Other issues for which there are trials include the meaning of aspirin resistance, and the impact of time of day and frequency of administration, which historically has not been considered important.

Clinical Topics: Diabetes and Cardiometabolic Disease, Dyslipidemia, Prevention, Vascular Medicine, Atherosclerotic Disease (CAD/PAD), Hypertension

Keywords: Aspirin, Clinical Trials Data Monitoring Committees, Diabetes Mellitus, Dyslipidemias, Hemorrhage, Hospitalization, Hypertension, Ischemic Attack, Transient, Japan, Medical Futility, Myocardial Infarction, Peripheral Vascular Diseases, Primary Prevention, Risk Factors, Stroke


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