Low-dose aspirin for primary prevention of cardiovascular events in japanese patients 60 years or older with atherosclerotic risk factors

A randomized clinical trial

Yasuo Ikeda, Kazuyuki Shimada, Tamio Teramoto, Shinichiro Uchiyama, Tsutomu Yamazaki, Shinichi Oikawa, Masahiro Sugawara, Katsuyuki Ando, Mitsuru Murata, Kenji Yokoyama, Naoki Ishizuka

Research output: Contribution to journalArticle

154 Citations (Scopus)

Abstract

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 100mg/d or no aspirin in addition to ongoing medications.

Main Outcomes and Measures: Composite primary outcomewas death from cardiovascular causes (myocardial infarction, stroke, and other cardiovascular causes), nonfatal stroke (ischemic or hemorrhagic, including undefined cerebrovascular events), and nonfatalmyocardial infarction. Secondary outcomes included individual end points.

Results The studywas 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 nonfatalmyocardial infarction, 20in 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 nonfatalmyocardial infarction (0.30 [95%CI, 0.19- 0.47] for aspirin vs0.58 [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 vs0.49 [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 vs0.51 [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 nonfatalmyocardial infarction among Japanese patients 60 years or older with atherosclerotic risk factors.

Original languageEnglish
Pages (from-to)2510-2520
Number of pages11
JournalJAMA - Journal of the American Medical Association
Volume312
Issue number23
DOIs
Publication statusPublished - 2014 Dec 17

Fingerprint

Primary Prevention
Aspirin
Randomized Controlled Trials
Infarction
Stroke
Japan
Clinical Trials Data Monitoring Committees
Myocardial Infarction
Outcome Assessment (Health Care)
Medical Futility
Health Priorities
Transient Ischemic Attack
Incidence

ASJC Scopus subject areas

  • Medicine(all)

Cite this

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, Yasuo; Shimada, Kazuyuki; Teramoto, Tamio; Uchiyama, Shinichiro; Yamazaki, Tsutomu; Oikawa, Shinichi; Sugawara, Masahiro; Ando, Katsuyuki; Murata, Mitsuru; Yokoyama, Kenji; Ishizuka, Naoki.

In: JAMA - Journal of the American Medical Association, Vol. 312, No. 23, 17.12.2014, p. 2510-2520.

Research output: Contribution to journalArticle

Ikeda, Yasuo ; Shimada, Kazuyuki ; Teramoto, Tamio ; Uchiyama, Shinichiro ; Yamazaki, Tsutomu ; Oikawa, Shinichi ; Sugawara, Masahiro ; Ando, Katsuyuki ; Murata, Mitsuru ; Yokoyama, Kenji ; Ishizuka, Naoki. / Low-dose aspirin for primary prevention of cardiovascular events in japanese patients 60 years or older with atherosclerotic risk factors : A randomized clinical trial. In: JAMA - Journal of the American Medical Association. 2014 ; Vol. 312, No. 23. pp. 2510-2520.
@article{c12189c17a2940d0a1a74f02c71fba44,
title = "Low-dose aspirin for primary prevention of cardiovascular events in japanese patients 60 years or older with atherosclerotic risk factors: A randomized clinical trial",
abstract = "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 100mg/d or no aspirin in addition to ongoing medications.Main Outcomes and Measures: Composite primary outcomewas death from cardiovascular causes (myocardial infarction, stroke, and other cardiovascular causes), nonfatal stroke (ischemic or hemorrhagic, including undefined cerebrovascular events), and nonfatalmyocardial infarction. Secondary outcomes included individual end points.Results The studywas 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 nonfatalmyocardial infarction, 20in 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 nonfatalmyocardial infarction (0.30 [95{\%}CI, 0.19- 0.47] for aspirin vs0.58 [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 vs0.49 [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 vs0.51 [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 nonfatalmyocardial infarction among Japanese patients 60 years or older with atherosclerotic risk factors.",
author = "Yasuo Ikeda and Kazuyuki Shimada and Tamio Teramoto and Shinichiro Uchiyama and Tsutomu Yamazaki and Shinichi Oikawa and Masahiro Sugawara and Katsuyuki Ando and Mitsuru Murata and Kenji Yokoyama and Naoki Ishizuka",
year = "2014",
month = "12",
day = "17",
doi = "10.1001/jama.2014.15690",
language = "English",
volume = "312",
pages = "2510--2520",
journal = "JAMA - Journal of the American Medical Association",
issn = "0002-9955",
publisher = "American Medical Association",
number = "23",

}

TY - JOUR

T1 - Low-dose aspirin for primary prevention of cardiovascular events in japanese patients 60 years or older with atherosclerotic risk factors

T2 - A randomized clinical trial

AU - Ikeda, Yasuo

AU - Shimada, Kazuyuki

AU - Teramoto, Tamio

AU - Uchiyama, Shinichiro

AU - Yamazaki, Tsutomu

AU - Oikawa, Shinichi

AU - Sugawara, Masahiro

AU - Ando, Katsuyuki

AU - Murata, Mitsuru

AU - Yokoyama, Kenji

AU - Ishizuka, Naoki

PY - 2014/12/17

Y1 - 2014/12/17

N2 - 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 100mg/d or no aspirin in addition to ongoing medications.Main Outcomes and Measures: Composite primary outcomewas death from cardiovascular causes (myocardial infarction, stroke, and other cardiovascular causes), nonfatal stroke (ischemic or hemorrhagic, including undefined cerebrovascular events), and nonfatalmyocardial infarction. Secondary outcomes included individual end points.Results The studywas 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 nonfatalmyocardial infarction, 20in 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 nonfatalmyocardial infarction (0.30 [95%CI, 0.19- 0.47] for aspirin vs0.58 [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 vs0.49 [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 vs0.51 [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 nonfatalmyocardial infarction among Japanese patients 60 years or older with atherosclerotic risk factors.

AB - 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 100mg/d or no aspirin in addition to ongoing medications.Main Outcomes and Measures: Composite primary outcomewas death from cardiovascular causes (myocardial infarction, stroke, and other cardiovascular causes), nonfatal stroke (ischemic or hemorrhagic, including undefined cerebrovascular events), and nonfatalmyocardial infarction. Secondary outcomes included individual end points.Results The studywas 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 nonfatalmyocardial infarction, 20in 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 nonfatalmyocardial infarction (0.30 [95%CI, 0.19- 0.47] for aspirin vs0.58 [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 vs0.49 [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 vs0.51 [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 nonfatalmyocardial infarction among Japanese patients 60 years or older with atherosclerotic risk factors.

UR - http://www.scopus.com/inward/record.url?scp=84919346036&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84919346036&partnerID=8YFLogxK

U2 - 10.1001/jama.2014.15690

DO - 10.1001/jama.2014.15690

M3 - Article

VL - 312

SP - 2510

EP - 2520

JO - JAMA - Journal of the American Medical Association

JF - JAMA - Journal of the American Medical Association

SN - 0002-9955

IS - 23

ER -