Aspirin With or Without Statin in Individuals Without Atherosclerotic Cardiovascular Disease Across Risk Categories

Safi U. Khan; Ahmad N. Lone; Neal S. Kleiman; Adeel Arshad; Vardhmaan Jain; Mahmoud Al Rifai; Hassaan B. Arshad; Sourbha S. Dani; Amit Khera; Pamela B. Morris; Vera Bittner; Khurram Nasir; Salim S. Virani

doi:10.1016/j.jacadv.2022.100197

Aspirin With or Without Statin in Individuals Without Atherosclerotic Cardiovascular Disease Across Risk Categories

Safi U. Khan, Ahmad N. Lone, Neal S. Kleiman, Adeel Arshad, Vardhmaan Jain, Mahmoud Al Rifai, Hassaan B. Arshad, Sourbha S. Dani, Amit Khera, Pamela B. Morris, Vera Bittner, Khurram Nasir, Salim S. Virani

Research output: Contribution to journal › Article › peer-review

4 Scopus citations

Abstract

Background: The effects of aspirin in adults without atherosclerotic cardiovascular disease (ASCVD), stratified by statin use across different ASCVD risks, remain uncertain. Objectives: The purpose of this study was to examine the effects of aspirin in adults without ASCVD, stratified by statin use across different ASCVD risks. Methods: We searched databases through March 2022 and selected randomized controlled trials of aspirin without ASCVD and follow-up of ≥1 year. We used random-effects models and estimated relative and absolute risks for cardiovascular outcomes, major bleeding, and mortality over 5 years. We calculated absolute risk differences assuming constant relative risks (RRs) across statin use and ASCVD risks. The Cholesterol Treatment Trialists Collaboration, and the ASCEND (A Study of Cardiovascular Events in Diabetes) trial were used to estimate baseline risks. Results: In 16 trials [171,215 individuals; median age, 64 (Q1-Q3: 60-65) years], aspirin vs control reduced myocardial infarction (MI) [RR: 0.85 (95% CI: 0.77-0.95)] but increased major bleeding [RR: 1.48 (95% CI: 1.32-1.66)]. Aspirin did not reduce mortality. Statin vs no statin was associated with lower bleeding and MI risk; the bleeding and MI risk were proportional to ASCVD risk. For every 10,000 adults, aspirin reduced MI (very low risk: 3 events as monotherapy or 1 event with statin; very high risk: 49 events as monotherapy or 37 events with statin) and increased major bleeding (very low risk: 21 events as monotherapy or 20 events with statin; very high risk: 98 events as monotherapy or 94 events with statin) proportional to baseline ASCVD risk. Conclusions: In adults without ASCVD, concomitant statin appeared to significantly reduce absolute risk reduction for MI associated with aspirin without influencing bleeding risk. The anticipated absolute risk of major bleeding with aspirin exceeds absolute MI benefits for every level of ASCVD risk.

Original language	English (US)
Article number	100197
Journal	JACC: Advances
Volume	2
Issue number	2
DOIs	https://doi.org/10.1016/j.jacadv.2022.100197
State	Published - Mar 2023

Keywords

aspirin
meta-analysis
primary prevention
statin

ASJC Scopus subject areas

Cardiology and Cardiovascular Medicine
Dentistry (miscellaneous)

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10.1016/j.jacadv.2022.100197

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Khan, S. U., Lone, A. N., Kleiman, N. S., Arshad, A., Jain, V., Al Rifai, M., Arshad, H. B., Dani, S. S., Khera, A., Morris, P. B., Bittner, V., Nasir, K., & Virani, S. S. (2023). Aspirin With or Without Statin in Individuals Without Atherosclerotic Cardiovascular Disease Across Risk Categories. JACC: Advances, 2(2), Article 100197. https://doi.org/10.1016/j.jacadv.2022.100197

@article{24ee255d2b42406f8d03e93da9601356,

title = "Aspirin With or Without Statin in Individuals Without Atherosclerotic Cardiovascular Disease Across Risk Categories",

abstract = "Background: The effects of aspirin in adults without atherosclerotic cardiovascular disease (ASCVD), stratified by statin use across different ASCVD risks, remain uncertain. Objectives: The purpose of this study was to examine the effects of aspirin in adults without ASCVD, stratified by statin use across different ASCVD risks. Methods: We searched databases through March 2022 and selected randomized controlled trials of aspirin without ASCVD and follow-up of ≥1 year. We used random-effects models and estimated relative and absolute risks for cardiovascular outcomes, major bleeding, and mortality over 5 years. We calculated absolute risk differences assuming constant relative risks (RRs) across statin use and ASCVD risks. The Cholesterol Treatment Trialists Collaboration, and the ASCEND (A Study of Cardiovascular Events in Diabetes) trial were used to estimate baseline risks. Results: In 16 trials [171,215 individuals; median age, 64 (Q1-Q3: 60-65) years], aspirin vs control reduced myocardial infarction (MI) [RR: 0.85 (95% CI: 0.77-0.95)] but increased major bleeding [RR: 1.48 (95% CI: 1.32-1.66)]. Aspirin did not reduce mortality. Statin vs no statin was associated with lower bleeding and MI risk; the bleeding and MI risk were proportional to ASCVD risk. For every 10,000 adults, aspirin reduced MI (very low risk: 3 events as monotherapy or 1 event with statin; very high risk: 49 events as monotherapy or 37 events with statin) and increased major bleeding (very low risk: 21 events as monotherapy or 20 events with statin; very high risk: 98 events as monotherapy or 94 events with statin) proportional to baseline ASCVD risk. Conclusions: In adults without ASCVD, concomitant statin appeared to significantly reduce absolute risk reduction for MI associated with aspirin without influencing bleeding risk. The anticipated absolute risk of major bleeding with aspirin exceeds absolute MI benefits for every level of ASCVD risk.",

keywords = "aspirin, meta-analysis, primary prevention, statin",

author = "Khan, {Safi U.} and Lone, {Ahmad N.} and Kleiman, {Neal S.} and Adeel Arshad and Vardhmaan Jain and {Al Rifai}, Mahmoud and Arshad, {Hassaan B.} and Dani, {Sourbha S.} and Amit Khera and Morris, {Pamela B.} and Vera Bittner and Khurram Nasir and Virani, {Salim S.}",

note = "Funding Information: Dr Virani has received research support from Department of Veterans Affairs, World Heart Federation, and Tahir and Jooma Family Honorarium: American College of Cardiology (Associate Editor for Innovations, acc.org). Dr Bittner has contracts between the University of Alabama at Birmingham and the respective sponsors; is on the Steering Committee of ODYSSEY OUTCOMES TRIAL (Sanofi and Regeneron); is the National Coordinator for the CLEAR OUTCOMES TRIAL (Esperion), DalGene Trial (Dalcor), and the STRENGTH Trial (AstraZeneca); is the site PI for the ORION trial (Novartis); is the coinvestigator for Academic; has Industry Collaboration between the School of Public Health and Amgen (PI: Muntner); has received direct payments for being a Senior Guest Editor for Circulation (American Heart Association); is an ongoing Editor in Chief for ACC SAP (American College of Cardiology); is on the Advisory Board for Pfizer (concluded at the end of 2021). All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Publisher Copyright: {\textcopyright} 2023 The Authors",

year = "2023",

month = mar,

doi = "10.1016/j.jacadv.2022.100197",

language = "English (US)",

volume = "2",

journal = "JACC: Advances",

issn = "2772-963X",

number = "2",

}

TY - JOUR

T1 - Aspirin With or Without Statin in Individuals Without Atherosclerotic Cardiovascular Disease Across Risk Categories

AU - Khan, Safi U.

AU - Lone, Ahmad N.

AU - Kleiman, Neal S.

AU - Arshad, Adeel

AU - Jain, Vardhmaan

AU - Al Rifai, Mahmoud

AU - Arshad, Hassaan B.

AU - Dani, Sourbha S.

AU - Khera, Amit

AU - Morris, Pamela B.

AU - Bittner, Vera

AU - Nasir, Khurram

AU - Virani, Salim S.

N1 - Funding Information: Dr Virani has received research support from Department of Veterans Affairs, World Heart Federation, and Tahir and Jooma Family Honorarium: American College of Cardiology (Associate Editor for Innovations, acc.org). Dr Bittner has contracts between the University of Alabama at Birmingham and the respective sponsors; is on the Steering Committee of ODYSSEY OUTCOMES TRIAL (Sanofi and Regeneron); is the National Coordinator for the CLEAR OUTCOMES TRIAL (Esperion), DalGene Trial (Dalcor), and the STRENGTH Trial (AstraZeneca); is the site PI for the ORION trial (Novartis); is the coinvestigator for Academic; has Industry Collaboration between the School of Public Health and Amgen (PI: Muntner); has received direct payments for being a Senior Guest Editor for Circulation (American Heart Association); is an ongoing Editor in Chief for ACC SAP (American College of Cardiology); is on the Advisory Board for Pfizer (concluded at the end of 2021). All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Publisher Copyright: © 2023 The Authors

PY - 2023/3

Y1 - 2023/3

N2 - Background: The effects of aspirin in adults without atherosclerotic cardiovascular disease (ASCVD), stratified by statin use across different ASCVD risks, remain uncertain. Objectives: The purpose of this study was to examine the effects of aspirin in adults without ASCVD, stratified by statin use across different ASCVD risks. Methods: We searched databases through March 2022 and selected randomized controlled trials of aspirin without ASCVD and follow-up of ≥1 year. We used random-effects models and estimated relative and absolute risks for cardiovascular outcomes, major bleeding, and mortality over 5 years. We calculated absolute risk differences assuming constant relative risks (RRs) across statin use and ASCVD risks. The Cholesterol Treatment Trialists Collaboration, and the ASCEND (A Study of Cardiovascular Events in Diabetes) trial were used to estimate baseline risks. Results: In 16 trials [171,215 individuals; median age, 64 (Q1-Q3: 60-65) years], aspirin vs control reduced myocardial infarction (MI) [RR: 0.85 (95% CI: 0.77-0.95)] but increased major bleeding [RR: 1.48 (95% CI: 1.32-1.66)]. Aspirin did not reduce mortality. Statin vs no statin was associated with lower bleeding and MI risk; the bleeding and MI risk were proportional to ASCVD risk. For every 10,000 adults, aspirin reduced MI (very low risk: 3 events as monotherapy or 1 event with statin; very high risk: 49 events as monotherapy or 37 events with statin) and increased major bleeding (very low risk: 21 events as monotherapy or 20 events with statin; very high risk: 98 events as monotherapy or 94 events with statin) proportional to baseline ASCVD risk. Conclusions: In adults without ASCVD, concomitant statin appeared to significantly reduce absolute risk reduction for MI associated with aspirin without influencing bleeding risk. The anticipated absolute risk of major bleeding with aspirin exceeds absolute MI benefits for every level of ASCVD risk.

AB - Background: The effects of aspirin in adults without atherosclerotic cardiovascular disease (ASCVD), stratified by statin use across different ASCVD risks, remain uncertain. Objectives: The purpose of this study was to examine the effects of aspirin in adults without ASCVD, stratified by statin use across different ASCVD risks. Methods: We searched databases through March 2022 and selected randomized controlled trials of aspirin without ASCVD and follow-up of ≥1 year. We used random-effects models and estimated relative and absolute risks for cardiovascular outcomes, major bleeding, and mortality over 5 years. We calculated absolute risk differences assuming constant relative risks (RRs) across statin use and ASCVD risks. The Cholesterol Treatment Trialists Collaboration, and the ASCEND (A Study of Cardiovascular Events in Diabetes) trial were used to estimate baseline risks. Results: In 16 trials [171,215 individuals; median age, 64 (Q1-Q3: 60-65) years], aspirin vs control reduced myocardial infarction (MI) [RR: 0.85 (95% CI: 0.77-0.95)] but increased major bleeding [RR: 1.48 (95% CI: 1.32-1.66)]. Aspirin did not reduce mortality. Statin vs no statin was associated with lower bleeding and MI risk; the bleeding and MI risk were proportional to ASCVD risk. For every 10,000 adults, aspirin reduced MI (very low risk: 3 events as monotherapy or 1 event with statin; very high risk: 49 events as monotherapy or 37 events with statin) and increased major bleeding (very low risk: 21 events as monotherapy or 20 events with statin; very high risk: 98 events as monotherapy or 94 events with statin) proportional to baseline ASCVD risk. Conclusions: In adults without ASCVD, concomitant statin appeared to significantly reduce absolute risk reduction for MI associated with aspirin without influencing bleeding risk. The anticipated absolute risk of major bleeding with aspirin exceeds absolute MI benefits for every level of ASCVD risk.

KW - aspirin

KW - meta-analysis

KW - primary prevention

KW - statin

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U2 - 10.1016/j.jacadv.2022.100197

DO - 10.1016/j.jacadv.2022.100197

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SN - 2772-963X

VL - 2

JO - JACC: Advances

JF - JACC: Advances

IS - 2

M1 - 100197

ER -

Aspirin With or Without Statin in Individuals Without Atherosclerotic Cardiovascular Disease Across Risk Categories

Abstract

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