Low-Dose Aspirin for Primary Prevention of Cardiovascular Events in Elderly Japanese Patients with Atherosclerotic Risk Factors: Subanalysis of a Randomized Clinical Trial (JPPP-70)

INTRODUCTION: This post hoc subanalysis of the randomized Japanese Primary Prevention Project investigated whether once-daily low-dose aspirin versus no aspirin reduced the risk of cardiovascular events (CVEs) in patients aged ≥ 70 years with atherosclerotic risk factors. METHODS: Patients aged < 70 years (young-old) or ≥ 70 years (old) with hypertension, dyslipidemia, or diabetes participated between 2005 and 2007. Patients were randomized 1: 1 to receive 100 mg enteric-coated aspirin once daily or no aspirin plus standard of care. The primary outcome was a composite of death from cardiovascular causes plus nonfatal stroke and nonfatal myocardial infarction. The secondary outcome was a composite of the primary outcome plus transient ischemic attack, angina pectoris, and arteriosclerotic disease requiring medical or surgical intervention. Old (n = 7971) and young-old (n = 6493) patients were followed up for a median 5. 02 years. RESULTS: Aspirin did not reduce the risk of primary (hazard ratio HR 0. 92 95% confidence interval CI 0. 74-1. 16; P = 0. 50) or secondary (0. 85 0. 70-1. 04; P = 0. 11) outcomes in patients aged ≥ 70 years. In old men with high-density lipoprotein < 40 mg/dL, treatment with low-dose aspirin was associated with a reduction in the incidence of the primary endpoint compared with the group not receiving aspirin (10/260 vs 22/250; HR 0. 44 95% CI 0. 20-0. 93; P = 0. 03). This subgroup was also found to contain significant larger proportions of patients with elevated body mass index, patients with diabetes mellitus, and smokers (P < 0. 001). Old patients also showed differences in bleeding outcomes. Serious extracranial hemorrhage requiring transfusion or hospitalization occurred significantly more frequently in the aspirin-treated group than in the non-aspirin-treated group (35 0. 88% vs 18 0. 45%; HR 1. 96 1. 11-3. 46; P = 0. 020). Gastrointestinal hemorrhage occurred significantly more frequently in the aspirin-treated group than the non-aspirin-treated group (63 1. 58% vs 18 0. 45%; relative risk RR 3. 5 2. 08-5. 90; P < 0. 0001). Cerebral hemorrhage (intracranial hemorrhage) tended to occur more frequently in the aspirin-treated group than the non-aspirin-treated group (22 0. 55% vs 11 0. 28%; RR 2. 01 0. 97-4. 14; P = 0. 058). Cerebral hemorrhage occurred significantly more frequently in old patients than in young-old patients (33 0. 41% vs 10 0. 15%; HR 2. 7 1. 34-5. 53; P = 0. 0055). Gastrointestinal hemorrhage occurred in a slightly higher proportion of old patients compared with young-old patients (81 1. 02% vs 53 0. 82%; RR 1. 2 0. 88-1. 76; P = 0. 21). DISCUSSION/CONCLUSIONS: Aspirin did not reduce the risk of the primary or secondary outcomes in old patients. Aspirin treatment may have reduced CVEs within a high CVE risk elderly population subgroup. Aspirin treatment in such a group requires caution, because of the increased risk of intracranial hemorrhage, severe extracranial hemorrhage requiring hospitalization or transfusion, and gastrointestinal bleeding in old patients receiving aspirin therapy. CLINICAL TRIAL REGISTRATION: The study is registered at ClinicalTrials. gov NCT00225849.