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

• Published in: JAMA : the journal of the American Medical Association 2014-12, Vol.312 (23), p.2510-2520
• Main Authors: Ikeda, Yasuo, Shimada, Kazuyuki, Teramoto, Tamio, Uchiyama, Shinichiro, Yamazaki, Tsutomu, Oikawa, Shinichi, Sugawara, Masahiro, Ando, Katsuyuki, Murata, Mitsuru, Yokoyama, Kenji, Ishizuka, Naoki
• Format: Article
• Language: English
• Subjects: Aged; Aged, 80 and over; Aspirin; Aspirin - administration & dosage; Aspirin - adverse effects; Atherosclerosis (general aspects, experimental research); Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; Cardiovascular disease; Cardiovascular Diseases - prevention & control; Clinical trials; Diabetes Mellitus; Disease prevention; Double-Blind Method; Dyslipidemias - complications; Female; General aspects; Hemorrhage - chemically induced; Humans; Hypertension - complications; Japan; Male; Medical sciences; Middle Aged; Myocardial Infarction - prevention & control; Older people; Platelet Aggregation Inhibitors - administration & dosage; Platelet Aggregation Inhibitors - adverse effects; Prevention and actions; Primary Prevention; Public health. Hygiene; Public health. Hygiene-occupational medicine; Risk Factors; Survival Analysis
• ISSN: 0098-7484; 1538-3598
• DOI: 10.1001/jama.2014.15690

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 requirin