Low-dose aspirin for primary prevention of cardiovascular events in Japanese patients 60 years or older with atherosclerotic risk factors: a randomized clinical trial.
OBJECTIVE
Prevention of atherosclerotic cardiovascular diseases is an important public health priority in Japan due to an aging population.


OBJECTIVE
To determine whether daily, low-dose aspirin reduces the incidence of cardiovascular events in older Japanese patients with multiple atherosclerotic risk factors.


METHODS
The Japanese Primary Prevention Project (JPPP) was a multicenter, open-label, randomized, parallel-group trial. Patients (N = 14,464) were aged 60 to 85 years, presenting with hypertension, dyslipidemia, or diabetes mellitus recruited by primary care physicians at 1007 clinics in Japan between March 2005 and June 2007, and were followed up for up to 6.5 years, with last follow-up in May 2012. A multidisciplinary expert panel (blinded to treatment assignments) adjudicated study outcomes.


METHODS
Patients were randomized 1:1 to enteric-coated aspirin 100 mg/d or no aspirin in addition to ongoing medications.


METHODS
Composite primary outcome was death from cardiovascular causes (myocardial infarction, stroke, and other cardiovascular causes), nonfatal stroke (ischemic or hemorrhagic, including undefined cerebrovascular events), and nonfatal myocardial infarction. Secondary outcomes included individual end points.


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. Patients with an occurrence of nonfatal stroke totaled 114 in the aspirin group and 108 in the no aspirin group; of nonfatal myocardial infarction, 20 in the aspirin group and 38 in the no aspirin group; of undefined cerebrovascular events, 3 in the aspirin group and 5 in the no aspirin group. The 5-year cumulative primary outcome event rate was not significantly different between the groups (2.77% [95% 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 = .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 = .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 = .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 = .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.


BACKGROUND
clinicaltrials.gov Identifier: NCT00225849.
Graduate School of Advanced Science and Engineering, Waseda University, Tokyo, Japan.
Yasuo
Y
Ikeda
Department of Cardiology, Shin-Oyama City Hospital, Tochigi, Japan.
Kazuyuki
K
Shimada
Teikyo Academic Research Center, Teikyo University, Tokyo, Japan.
Tamio
T
Teramoto
Clinical Research Center for Medicine, International University of Health and Welfare, Tokyo, Japan.
Shinichiro
S
Uchiyama
Clinical Research Support Center, Center for Epidemiology and Preventive Medicine, The University of Tokyo Hospital, Japan.
Tsutomu
T
Yamazaki
Diabetes and Lifestyle Disease Center, Fukujuji Hospital, Tokyo, Japan.
Shinichi
S
Oikawa
Department of Internal Medicine, Sugawara Medical Clinic, Tokyo, Japan.
Masahiro
M
Sugawara
Department of Internal Medicine, Kitamura Memorial Clinic, Tokyo, Japan.
Katsuyuki
K
Ando
Department of Laboratory Medicine, Keio University School of Medicine, Tokyo, Japan.
Mitsuru
M
Murata
Department of Hematology, Tokai University Hachioji Hospital, Tokyo, Japan.
Kenji
K
Yokoyama
Clinical Trial Department, Cancer Institute Hospital, Tokyo, Japan.
Naoki
N
Ishizuka
D000368:Aged; D000369:Aged, 80 and over; D001241:Aspirin / Q000008:administration & dosage* / Q000009:adverse effects; D002318:Cardiovascular Diseases / Q000517:prevention & control*; D003920:Diabetes Mellitus; D004311:Double-Blind Method; D050171:Dyslipidemias / Q000150:complications; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D006973:Hypertension / Q000150:complications; D007564:Japan; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000517:prevention & control*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D011322:Primary Prevention; D012307:Risk Factors; D016019:Survival Analysis
D010975:Platelet Aggregation Inhibitors; D001241:Aspirin