1. JAMA. 2014 Dec 17;312(23):2510-20. doi: 10.1001/jama.2014.15690.

Low-dose aspirin for primary prevention of cardiovascular events in Japanese
patients 60 years or older with atherosclerotic risk factors: a randomized
clinical trial.

Ikeda Y(1), Shimada K(2), Teramoto T(3), Uchiyama S(4), Yamazaki T(5), Oikawa
S(6), Sugawara M(7), Ando K(8), Murata M(9), Yokoyama K(10), Ishizuka N(11).

Author information: 
(1)Graduate School of Advanced Science and Engineering, Waseda University, Tokyo,
Japan.
(2)Department of Cardiology, Shin-Oyama City Hospital, Tochigi, Japan.
(3)Teikyo Academic Research Center, Teikyo University, Tokyo, Japan.
(4)Clinical Research Center for Medicine, International University of Health and 
Welfare, Tokyo, Japan.
(5)Clinical Research Support Center, Center for Epidemiology and Preventive
Medicine, The University of Tokyo Hospital, Japan.
(6)Diabetes and Lifestyle Disease Center, Fukujuji Hospital, Tokyo, Japan.
(7)Department of Internal Medicine, Sugawara Medical Clinic, Tokyo, Japan.
(8)Department of Internal Medicine, Kitamura Memorial Clinic, Tokyo, Japan.
(9)Department of Laboratory Medicine, Keio University School of Medicine, Tokyo, 
Japan.
(10)Department of Hematology, Tokai University Hachioji Hospital, Tokyo, Japan.
(11)Clinical Trial Department, Cancer Institute Hospital, Tokyo, Japan.

Comment in
    JAMA. 2014 Dec 17;312(23):2503-4.
    Nat Rev Cardiol. 2015 Jan;12(1):3.
    Praxis (Bern 1994). 2015 Feb 11;104(4):205-6.
    JAMA. 2015 Apr 14;313(14):1473.
    JAMA. 2015 Apr 14;313(14):1473-4.
    JAMA. 2015 Apr 14;313(14):1473.

IMPORTANCE: 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.
DESIGN, SETTING, AND PARTICIPANTS: 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.
INTERVENTIONS: Patients were randomized 1:1 to enteric-coated aspirin 100 mg/d or
no aspirin in addition to ongoing medications.
MAIN OUTCOMES AND MEASURES: 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 AND RELEVANCE: 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.
TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00225849.

DOI: 10.1001/jama.2014.15690 
PMID: 25401325  [Indexed for MEDLINE]