Low-Dose Aspirin for Primary Prevention of Cardiovascular Events in Elderly Japanese Patients with Atherosclerotic Risk Factors: Subanalysis of a Randomized Clinical Trial (JPPP-70)

On behalf of the Japanese Primary Prevention Project (JPPP) Study Group

Research output: Contribution to journalArticle

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Abstract

Introduction: 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].

Original languageEnglish
Pages (from-to)299-311
Number of pages13
JournalAmerican Journal of Cardiovascular Drugs
Volume19
Issue number3
DOIs
Publication statusPublished - 2019 Jun 1

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Primary Prevention
Aspirin
Randomized Controlled Trials
Hemorrhage
Gastrointestinal Hemorrhage
Intracranial Hemorrhages
Cerebral Hemorrhage
Hospitalization
Confidence Intervals
Transient Ischemic Attack
Angina Pectoris
HDL Lipoproteins
Therapeutics
Standard of Care
Dyslipidemias
Cause of Death
Diabetes Mellitus
Body Mass Index
Stroke
Myocardial Infarction

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Pharmacology (medical)

Cite this

Low-Dose Aspirin for Primary Prevention of Cardiovascular Events in Elderly Japanese Patients with Atherosclerotic Risk Factors : Subanalysis of a Randomized Clinical Trial (JPPP-70). / On behalf of the Japanese Primary Prevention Project (JPPP) Study Group.

In: American Journal of Cardiovascular Drugs, Vol. 19, No. 3, 01.06.2019, p. 299-311.

Research output: Contribution to journalArticle

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title = "Low-Dose Aspirin for Primary Prevention of Cardiovascular Events in Elderly Japanese Patients with Atherosclerotic Risk Factors: Subanalysis of a Randomized Clinical Trial (JPPP-70)",
abstract = "Introduction: 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].",
author = "{On behalf of the Japanese Primary Prevention Project (JPPP) Study Group} and Masahiro Sugawara and Yoshio Goto and Tsutomu Yamazaki and Tamio Teramoto and Shinichi Oikawa and Kazuyuki Shimada and Shinichiro Uchiyama and Katsuyuki Ando and Naoki Ishizuka and Mitsuru Murata and Kenji Yokoyama and Yukari Uemura and Yasuo Ikeda and Masahiro Sugawara and Nobuhiro Yamada and Toshiro Fujita and Saichi Hosoda and Hideki Origasa and Yukito Shinohara and Akira Yamamoto and Masayasu Matsumoto and Kazuo Minematsu and Hiroyuki Daida and Hisao Ogawa",
year = "2019",
month = "6",
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TY - JOUR

T1 - Low-Dose Aspirin for Primary Prevention of Cardiovascular Events in Elderly Japanese Patients with Atherosclerotic Risk Factors

T2 - Subanalysis of a Randomized Clinical Trial (JPPP-70)

AU - On behalf of the Japanese Primary Prevention Project (JPPP) Study Group

AU - Sugawara, Masahiro

AU - Goto, Yoshio

AU - Yamazaki, Tsutomu

AU - Teramoto, Tamio

AU - Oikawa, Shinichi

AU - Shimada, Kazuyuki

AU - Uchiyama, Shinichiro

AU - Ando, Katsuyuki

AU - Ishizuka, Naoki

AU - Murata, Mitsuru

AU - Yokoyama, Kenji

AU - Uemura, Yukari

AU - Ikeda, Yasuo

AU - Sugawara, Masahiro

AU - Yamada, Nobuhiro

AU - Fujita, Toshiro

AU - Hosoda, Saichi

AU - Origasa, Hideki

AU - Shinohara, Yukito

AU - Yamamoto, Akira

AU - Matsumoto, Masayasu

AU - Minematsu, Kazuo

AU - Daida, Hiroyuki

AU - Ogawa, Hisao

PY - 2019/6/1

Y1 - 2019/6/1

N2 - Introduction: 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].

AB - Introduction: 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].

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U2 - 10.1007/s40256-018-0313-0

DO - 10.1007/s40256-018-0313-0

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AN - SCOPUS:85058942804

VL - 19

SP - 299

EP - 311

JO - American Journal of Cardiovascular Drugs

JF - American Journal of Cardiovascular Drugs

SN - 1175-3277

IS - 3

ER -