Aspirin Dosing for Secondary Prevention of Atherosclerotic Cardiovascular Disease in Patients Treated With P2Y12 Inhibitors

Saket Girotra; Amanda Stebbins; Lisa Wruck; Guillaume Marquis-Gravel; Kamal Gupta; Peter Farrehi; Catherine P. Benziger; Mark B. Effron; Jeffrey Whittle; Daniel Muñoz; Sunil Kripalani; R. David Anderson; Sandeep K. Jain; Tamar S. Polonsky; Faraz S. Ahmad; Matthew T. Roe; Russell L. Rothman; Robert A. Harrington; Adrian F. Hernandez; W. Schuyler Jones

doi:10.1161/JAHA.123.030385

Aspirin Dosing for Secondary Prevention of Atherosclerotic Cardiovascular Disease in Patients Treated With P2Y12 Inhibitors

Saket Girotra^*, Amanda Stebbins, Lisa Wruck, Guillaume Marquis-Gravel, Kamal Gupta, Peter Farrehi, Catherine P. Benziger, Mark B. Effron, Jeffrey Whittle, Daniel Muñoz, Sunil Kripalani, R. David Anderson, Sandeep K. Jain, Tamar S. Polonsky, Faraz S. Ahmad, Matthew T. Roe, Russell L. Rothman, Robert A. Harrington, Adrian F. Hernandez, W. Schuyler Jones

^*Corresponding author for this work

Medicine, Cardiology Division

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

1 Scopus citations

Abstract

BACKGROUND: The ADAPTABLE (Aspirin Dosing: A Patient-Centric Trial Assessing Benefits and Long-Term Effectiveness) was a large, pragmatic, randomized controlled trial that found no difference between high-versus low-dose aspirin for secondary prevention of atherosclerotic cardiovascular disease. Whether concomitant P2Y12 inhibitor therapy modifies the effect of aspirin dose on clinical events remains unclear. METHODS AND RESULTS: Participants in ADAPTABLE were stratified according to baseline use of clopidogrel or prasugrel (P2Y12 group). The primary effectiveness end point was a composite of death, myocardial infarction, or stroke; and the primary safety end point was major bleeding requiring blood transfusions. We used multivariable Cox regression to compare the relative effectiveness and safety of aspirin dose within P2Y12 and non-P2Y12 groups. Of 13 815 (91.6%) participants with available data, 3051 (22.1%) were receiving clopidogrel (2849 [93.4%]) or prasugrel (203 [6.7%]) at baseline. P2Y12 inhibitor use was associated with higher risk of the primary effectiveness end point (10.86% versus 6.31%; adjusted hazard ratio [HR], 1.40 [95% CI, 1.22–1.62]) but was not associated with bleeding (0.95% versus 0.53%; adjusted HR, 1.42 [95% CI, 0.91–2.22]). We found no interaction in the relative effectiveness and safety of high-versus low-dose aspirin by P2Y12 inhibitor use. Overall, dose switching or discontinuation was more common in the high-dose compared with low-dose aspirin group, but the pattern was not modified by P2Y12 inhibitor use. CONCLUSIONS: In this prespecified analysis of ADAPTABLE, we found that the relative effectiveness and safety of high-versus low-dose aspirin was not modified by baseline P2Y12 inhibitor use. REGISTRATION: https://www.clinical.trials.gov. Unique identifier: NCT02697916.

Original language	English (US)
Article number	e030385
Journal	Journal of the American Heart Association
Volume	12
Issue number	20
DOIs	https://doi.org/10.1161/JAHA.123.030385
State	Published - Oct 17 2023

Funding

Dr Girotra receives funding from the American Heart Association for editorial work. Dr Marquis-Gravel reports compensation for consultant services from Cardiovascular Systems Inc, Canadian Heart Research Center, KYE, Novartis, Pfizer, JAMP Pharma, HLS Ther, and Bristol-Myers Squibb Canada, Bayer, Pendophar, Boston Scientific Corporation, and Amgen Canada. Dr. Marquis-Gravel also receives compensation from Novartis for other services and grants from Bayer. Dr Effron reports compensation from Eli Lilly and Company for other services and stock holdings in Eli Lilly and Company. Dr Whittle reports grants from Patient-Centered Outcomes Research Institute and employment by US Department of Veterans Affairs. Dr Jain reports grants from Boston Scientific Corporation and grants from Medtronic USA, Inc. Dr Roe reports stock holdings in AstraZeneca; compensation from F. Hoffmann-La Roche for data and safety monitoring services; stock options in Verana Health; employment by AstraZeneca; compensation from Novo Nordisk for end point review committee services; and compensation from Regeneron Pharmaceuticals, Inc for data and safety monitoring services. Dr Rothman reports grants from Patient-Centered Outcomes Research Institute. Dr Harrington reports grants from The Medicines Company; service as Board of Directors for Cytokinetics; grants from Janssen Global Services, LLC; grants from AstraZeneca; employment by Robert A Harrington; and compensation from Bristol-Myers Squibb for consultant services. Dr Hernandez reports grants from Intellia Therapeutics; compensation from Prolaio for consultant services; grants from Bayer; compensation from Eli Lilly and Company for consultant services; compensation from Novo Nordisk for consultant services; employment by Duke Clinical Research Institute; compensation from Intercept Pharmaceuticals, Inc, for data and safety monitoring services; grants from Boehringer Ingelheim; compensation from CSL Behring for consultant services; compensation from Boehringer Ingelheim for consultant services; compensation from Amgen for consultant services; compensation from Novartis for consultant services; grants from Verily; compensation from Merck for consultant services; grants from American Regent; compensation from AstraZeneca for consultant services; compensation from Eidos for data and safety monitoring services; compensation from Cytokinetics for consultant services; grants from Novo Nordisk Inc; grants from Novartis; grants from Merck; compensation from Bayer for consultant services; grants from AstraZeneca; compensation from Boston Scientific Corporation for consultant services; and compensation from Intellia Therapeutics for consultant services. Dr Jones reports grants from Bayer. The remaining authors have no disclosures to report. Dr Girotra is supported by the National Heart, Lung, and Blood Institute (NHLBI; 1R01HL160734, 1R01HL166305, and R56HL158803). Dr Ahmad is supported by grants from the NHLBI (K23HL155970) and the American Heart Association (number 856917).

Keywords

aspirin
atherosclerotic cardiovascular disease
secondary prevention

ASJC Scopus subject areas

Cardiology and Cardiovascular Medicine

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1161/JAHA.123.030385

Cite this

Girotra, S., Stebbins, A., Wruck, L., Marquis-Gravel, G., Gupta, K., Farrehi, P., Benziger, C. P., Effron, M. B., Whittle, J., Muñoz, D., Kripalani, S., Anderson, R. D., Jain, S. K., Polonsky, T. S., Ahmad, F. S., Roe, M. T., Rothman, R. L., Harrington, R. A., Hernandez, A. F., & Jones, W. S. (2023). Aspirin Dosing for Secondary Prevention of Atherosclerotic Cardiovascular Disease in Patients Treated With P2Y12 Inhibitors. Journal of the American Heart Association, 12(20), Article e030385. https://doi.org/10.1161/JAHA.123.030385

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title = "Aspirin Dosing for Secondary Prevention of Atherosclerotic Cardiovascular Disease in Patients Treated With P2Y12 Inhibitors",

abstract = "BACKGROUND: The ADAPTABLE (Aspirin Dosing: A Patient-Centric Trial Assessing Benefits and Long-Term Effectiveness) was a large, pragmatic, randomized controlled trial that found no difference between high-versus low-dose aspirin for secondary prevention of atherosclerotic cardiovascular disease. Whether concomitant P2Y12 inhibitor therapy modifies the effect of aspirin dose on clinical events remains unclear. METHODS AND RESULTS: Participants in ADAPTABLE were stratified according to baseline use of clopidogrel or prasugrel (P2Y12 group). The primary effectiveness end point was a composite of death, myocardial infarction, or stroke; and the primary safety end point was major bleeding requiring blood transfusions. We used multivariable Cox regression to compare the relative effectiveness and safety of aspirin dose within P2Y12 and non-P2Y12 groups. Of 13 815 (91.6%) participants with available data, 3051 (22.1%) were receiving clopidogrel (2849 [93.4%]) or prasugrel (203 [6.7%]) at baseline. P2Y12 inhibitor use was associated with higher risk of the primary effectiveness end point (10.86% versus 6.31%; adjusted hazard ratio [HR], 1.40 [95% CI, 1.22–1.62]) but was not associated with bleeding (0.95% versus 0.53%; adjusted HR, 1.42 [95% CI, 0.91–2.22]). We found no interaction in the relative effectiveness and safety of high-versus low-dose aspirin by P2Y12 inhibitor use. Overall, dose switching or discontinuation was more common in the high-dose compared with low-dose aspirin group, but the pattern was not modified by P2Y12 inhibitor use. CONCLUSIONS: In this prespecified analysis of ADAPTABLE, we found that the relative effectiveness and safety of high-versus low-dose aspirin was not modified by baseline P2Y12 inhibitor use. REGISTRATION: https://www.clinical.trials.gov. Unique identifier: NCT02697916.",

keywords = "aspirin, atherosclerotic cardiovascular disease, secondary prevention",

author = "Saket Girotra and Amanda Stebbins and Lisa Wruck and Guillaume Marquis-Gravel and Kamal Gupta and Peter Farrehi and Benziger, {Catherine P.} and Effron, {Mark B.} and Jeffrey Whittle and Daniel Mu{\~n}oz and Sunil Kripalani and Anderson, {R. David} and Jain, {Sandeep K.} and Polonsky, {Tamar S.} and Ahmad, {Faraz S.} and Roe, {Matthew T.} and Rothman, {Russell L.} and Harrington, {Robert A.} and Hernandez, {Adrian F.} and Jones, {W. Schuyler}",

note = "Publisher Copyright: {\textcopyright} 2023 The Authors.",

year = "2023",

month = oct,

day = "17",

doi = "10.1161/JAHA.123.030385",

language = "English (US)",

volume = "12",

journal = "Journal of the American Heart Association",

issn = "2047-9980",

publisher = "American Heart Association Inc.",

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Girotra, S, Stebbins, A, Wruck, L, Marquis-Gravel, G, Gupta, K, Farrehi, P, Benziger, CP, Effron, MB, Whittle, J, Muñoz, D, Kripalani, S, Anderson, RD, Jain, SK, Polonsky, TS, Ahmad, FS, Roe, MT, Rothman, RL, Harrington, RA, Hernandez, AF & Jones, WS 2023, 'Aspirin Dosing for Secondary Prevention of Atherosclerotic Cardiovascular Disease in Patients Treated With P2Y12 Inhibitors', Journal of the American Heart Association, vol. 12, no. 20, e030385. https://doi.org/10.1161/JAHA.123.030385

TY - JOUR

T1 - Aspirin Dosing for Secondary Prevention of Atherosclerotic Cardiovascular Disease in Patients Treated With P2Y12 Inhibitors

AU - Girotra, Saket

AU - Stebbins, Amanda

AU - Wruck, Lisa

AU - Marquis-Gravel, Guillaume

AU - Gupta, Kamal

AU - Farrehi, Peter

AU - Benziger, Catherine P.

AU - Effron, Mark B.

AU - Whittle, Jeffrey

AU - Muñoz, Daniel

AU - Kripalani, Sunil

AU - Anderson, R. David

AU - Jain, Sandeep K.

AU - Polonsky, Tamar S.

AU - Ahmad, Faraz S.

AU - Roe, Matthew T.

AU - Rothman, Russell L.

AU - Harrington, Robert A.

AU - Hernandez, Adrian F.

AU - Jones, W. Schuyler

PY - 2023/10/17

Y1 - 2023/10/17

N2 - BACKGROUND: The ADAPTABLE (Aspirin Dosing: A Patient-Centric Trial Assessing Benefits and Long-Term Effectiveness) was a large, pragmatic, randomized controlled trial that found no difference between high-versus low-dose aspirin for secondary prevention of atherosclerotic cardiovascular disease. Whether concomitant P2Y12 inhibitor therapy modifies the effect of aspirin dose on clinical events remains unclear. METHODS AND RESULTS: Participants in ADAPTABLE were stratified according to baseline use of clopidogrel or prasugrel (P2Y12 group). The primary effectiveness end point was a composite of death, myocardial infarction, or stroke; and the primary safety end point was major bleeding requiring blood transfusions. We used multivariable Cox regression to compare the relative effectiveness and safety of aspirin dose within P2Y12 and non-P2Y12 groups. Of 13 815 (91.6%) participants with available data, 3051 (22.1%) were receiving clopidogrel (2849 [93.4%]) or prasugrel (203 [6.7%]) at baseline. P2Y12 inhibitor use was associated with higher risk of the primary effectiveness end point (10.86% versus 6.31%; adjusted hazard ratio [HR], 1.40 [95% CI, 1.22–1.62]) but was not associated with bleeding (0.95% versus 0.53%; adjusted HR, 1.42 [95% CI, 0.91–2.22]). We found no interaction in the relative effectiveness and safety of high-versus low-dose aspirin by P2Y12 inhibitor use. Overall, dose switching or discontinuation was more common in the high-dose compared with low-dose aspirin group, but the pattern was not modified by P2Y12 inhibitor use. CONCLUSIONS: In this prespecified analysis of ADAPTABLE, we found that the relative effectiveness and safety of high-versus low-dose aspirin was not modified by baseline P2Y12 inhibitor use. REGISTRATION: https://www.clinical.trials.gov. Unique identifier: NCT02697916.

AB - BACKGROUND: The ADAPTABLE (Aspirin Dosing: A Patient-Centric Trial Assessing Benefits and Long-Term Effectiveness) was a large, pragmatic, randomized controlled trial that found no difference between high-versus low-dose aspirin for secondary prevention of atherosclerotic cardiovascular disease. Whether concomitant P2Y12 inhibitor therapy modifies the effect of aspirin dose on clinical events remains unclear. METHODS AND RESULTS: Participants in ADAPTABLE were stratified according to baseline use of clopidogrel or prasugrel (P2Y12 group). The primary effectiveness end point was a composite of death, myocardial infarction, or stroke; and the primary safety end point was major bleeding requiring blood transfusions. We used multivariable Cox regression to compare the relative effectiveness and safety of aspirin dose within P2Y12 and non-P2Y12 groups. Of 13 815 (91.6%) participants with available data, 3051 (22.1%) were receiving clopidogrel (2849 [93.4%]) or prasugrel (203 [6.7%]) at baseline. P2Y12 inhibitor use was associated with higher risk of the primary effectiveness end point (10.86% versus 6.31%; adjusted hazard ratio [HR], 1.40 [95% CI, 1.22–1.62]) but was not associated with bleeding (0.95% versus 0.53%; adjusted HR, 1.42 [95% CI, 0.91–2.22]). We found no interaction in the relative effectiveness and safety of high-versus low-dose aspirin by P2Y12 inhibitor use. Overall, dose switching or discontinuation was more common in the high-dose compared with low-dose aspirin group, but the pattern was not modified by P2Y12 inhibitor use. CONCLUSIONS: In this prespecified analysis of ADAPTABLE, we found that the relative effectiveness and safety of high-versus low-dose aspirin was not modified by baseline P2Y12 inhibitor use. REGISTRATION: https://www.clinical.trials.gov. Unique identifier: NCT02697916.

KW - aspirin

KW - atherosclerotic cardiovascular disease

KW - secondary prevention

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UR - http://www.scopus.com/inward/citedby.url?scp=85175549903&partnerID=8YFLogxK

U2 - 10.1161/JAHA.123.030385

DO - 10.1161/JAHA.123.030385

M3 - Article

C2 - 37830344

AN - SCOPUS:85175549903

SN - 2047-9980

VL - 12

JO - Journal of the American Heart Association

JF - Journal of the American Heart Association

IS - 20

M1 - e030385

ER -

Aspirin Dosing for Secondary Prevention of Atherosclerotic Cardiovascular Disease in Patients Treated With P2Y12 Inhibitors

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UN SDGs

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