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].