Comparative effectiveness of aspirin dosing in cardiovascular disease

W. Schuyler Jones; Hillary Mulder; Lisa M. Wruck; Michael J. Pencina; Sunil Kripalani; Daniel Muñoz; David L. Crenshaw; Mark B. Effron; Richard N. Re; Kamal Gupta; R. David Anderson; Carl J. Pepine; Eileen M. Handberg; Brittney R. Manning; Sandeep K. Jain; Saket Girotra; Danielle Riley; Darren A. DeWalt; Jeff Whittle; Ythan H. Goldberg; Veronique L. Roger; Rachel Hess; Catherine P. Benziger; Peter Farrehi; Li Zhou; Daniel E. Ford; Kevin Haynes; Jeffrey J. VanWormer; Kirk U. Knowlton; Jennifer L. Kraschnewski; Tamar S. Polonsky; Dan J. Fintel; Faraz S. Ahmad; James C. McClay; James R. Campbell; Douglas S. Bell; Gregg C. Fonarow; Steven M. Bradley; Anuradha Paranjape; Matthew T. Roe; Holly R. Robertson; Lesley H. Curtis; Amber G. Sharlow; Lisa G. Berdan; Bradley G. Hammill; Debra F. Harris; Laura G. Qualls; Guillaume Marquis-Gravel; Madelaine F. Modrow; Gregory M. Marcus; Thomas W. Carton; Elizabeth Nauman; Lemuel R. Waitman; Abel N. Kho; Elizabeth A. Shenkman; Kathleen M. McTigue; Rainu Kaushal; Frederick A. Masoudi; Elliott M. Antman; Desiree R. Davidson; Kevin Edgley; James G. Merritt; Linda S. Brown; Doris N. Zemon; Thomas E. McCormick; Jacqueline D. Alikhaani; Kenneth C. Gregoire; Russell L. Rothman; Robert A. Harrington; Adrian F. Hernandez; Oana A. Sandu

doi:10.1056/NEJMoa2102137

Comparative effectiveness of aspirin dosing in cardiovascular disease

W. Schuyler Jones, Hillary Mulder, Lisa M. Wruck, Michael J. Pencina, Sunil Kripalani, Daniel Muñoz, David L. Crenshaw, Mark B. Effron, Richard N. Re, Kamal Gupta, R. David Anderson, Carl J. Pepine, Eileen M. Handberg, Brittney R. Manning, Sandeep K. Jain, Saket Girotra, Danielle Riley, Darren A. DeWalt, Jeff Whittle, Ythan H. GoldbergVeronique L. Roger, Rachel Hess, Catherine P. Benziger, Peter Farrehi, Li Zhou, Daniel E. Ford, Kevin Haynes, Jeffrey J. VanWormer, Kirk U. Knowlton, Jennifer L. Kraschnewski, Tamar S. Polonsky, Dan J. Fintel, Faraz S. Ahmad, James C. McClay, James R. Campbell, Douglas S. Bell, Gregg C. Fonarow, Steven M. Bradley, Anuradha Paranjape, Matthew T. Roe, Holly R. Robertson, Lesley H. Curtis, Amber G. Sharlow, Lisa G. Berdan, Bradley G. Hammill, Debra F. Harris, Laura G. Qualls, Guillaume Marquis-Gravel, Madelaine F. Modrow, Gregory M. Marcus, Thomas W. Carton, Elizabeth Nauman, Lemuel R. Waitman, Abel N. Kho, Elizabeth A. Shenkman, Kathleen M. McTigue, Rainu Kaushal, Frederick A. Masoudi, Elliott M. Antman, Desiree R. Davidson, Kevin Edgley, James G. Merritt, Linda S. Brown, Doris N. Zemon, Thomas E. McCormick, Jacqueline D. Alikhaani, Kenneth C. Gregoire, Russell L. Rothman, Robert A. Harrington, Adrian F. Hernandez, Oana A. Sandu

Quantitative Health Sciences

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

Abstract

The appropriate dose of aspirin to lower the risk of death, myocardial infarction, and stroke and to minimize major bleeding in patients with established atherosclerotic cardiovascular disease is a subject of controversy. METHODS Using an open-label, pragmatic design, we randomly assigned patients with established atherosclerotic cardiovascular disease to a strategy of 81 mg or 325 mg of aspirin per day. The primary effectiveness outcome was a composite of death from any cause, hospitalization for myocardial infarction, or hospitalization for stroke, assessed in a time-to-event analysis. The primary safety outcome was hospitalization for major bleeding, also assessed in a time-to-event analysis. RESULTS A total of 15,076 patients were followed for a median of 26.2 months (interquartile range [IQR], 19.0 to 34.9). Before randomization, 13,537 (96.0% of those with available information on previous aspirin use) were already taking aspirin, and 85.3% of these patients were previously taking 81 mg of daily aspirin. Death, hospitalization for myocardial infarction, or hospitalization for stroke occurred in 590 patients (estimated percentage, 7.28%) in the 81-mg group and 569 patients (estimated percentage, 7.51%) in the 325-mg group (hazard ratio, 1.02; 95% confidence interval [CI], 0.91 to 1.14). Hospitalization for major bleeding occurred in 53 patients (estimated percentage, 0.63%) in the 81-mg group and 44 patients (estimated percentage, 0.60%) in the 325-mg group (hazard ratio, 1.18; 95% CI, 0.79 to 1.77). Patients assigned to 325 mg had a higher incidence of dose switching than those assigned to 81 mg (41.6% vs. 7.1%) and fewer median days of exposure to the assigned dose (434 days [IQR, 139 to 737] vs. 650 days [IQR, 415 to 922]). CONCLUSIONS In this pragmatic trial involving patients with established cardiovascular disease, there was substantial dose switching to 81 mg of daily aspirin and no significant differences in cardiovascular events or major bleeding between patients assigned to 81 mg and those assigned to 325 mg of aspirin daily.

Original language	English (US)
Pages (from-to)	1981-1990
Number of pages	10
Journal	New England Journal of Medicine
Volume	384
Issue number	21
DOIs	https://doi.org/10.1056/NEJMoa2102137
State	Published - May 27 2021

ASJC Scopus subject areas

General Medicine

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10.1056/NEJMoa2102137

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Jones, W. S., Mulder, H., Wruck, L. M., Pencina, M. J., Kripalani, S., Muñoz, D., Crenshaw, D. L., Effron, M. B., Re, R. N., Gupta, K., David Anderson, R., Pepine, C. J., Handberg, E. M., Manning, B. R., Jain, S. K., Girotra, S., Riley, D., DeWalt, D. A., Whittle, J., ... Sandu, O. A. (2021). Comparative effectiveness of aspirin dosing in cardiovascular disease. New England Journal of Medicine, 384(21), 1981-1990. https://doi.org/10.1056/NEJMoa2102137

Jones, WS, Mulder, H, Wruck, LM, Pencina, MJ, Kripalani, S, Muñoz, D, Crenshaw, DL, Effron, MB, Re, RN, Gupta, K, David Anderson, R, Pepine, CJ, Handberg, EM, Manning, BR, Jain, SK, Girotra, S, Riley, D, DeWalt, DA, Whittle, J, Goldberg, YH, Roger, VL, Hess, R, Benziger, CP, Farrehi, P, Zhou, L, Ford, DE, Haynes, K, VanWormer, JJ, Knowlton, KU, Kraschnewski, JL, Polonsky, TS, Fintel, DJ, Ahmad, FS, McClay, JC, Campbell, JR, Bell, DS, Fonarow, GC, Bradley, SM, Paranjape, A, Roe, MT, Robertson, HR, Curtis, LH, Sharlow, AG, Berdan, LG, Hammill, BG, Harris, DF, Qualls, LG, Marquis-Gravel, G, Modrow, MF, Marcus, GM, Carton, TW, Nauman, E, Waitman, LR, Kho, AN, Shenkman, EA, McTigue, KM, Kaushal, R, Masoudi, FA, Antman, EM, Davidson, DR, Edgley, K, Merritt, JG, Brown, LS, Zemon, DN, McCormick, TE, Alikhaani, JD, Gregoire, KC, Rothman, RL, Harrington, RA, Hernandez, AF & Sandu, OA 2021, 'Comparative effectiveness of aspirin dosing in cardiovascular disease', New England Journal of Medicine, vol. 384, no. 21, pp. 1981-1990. https://doi.org/10.1056/NEJMoa2102137

@article{d2f17a21f0ed47b2a0274874ba96adaf,

title = "Comparative effectiveness of aspirin dosing in cardiovascular disease",

abstract = "The appropriate dose of aspirin to lower the risk of death, myocardial infarction, and stroke and to minimize major bleeding in patients with established atherosclerotic cardiovascular disease is a subject of controversy. METHODS Using an open-label, pragmatic design, we randomly assigned patients with established atherosclerotic cardiovascular disease to a strategy of 81 mg or 325 mg of aspirin per day. The primary effectiveness outcome was a composite of death from any cause, hospitalization for myocardial infarction, or hospitalization for stroke, assessed in a time-to-event analysis. The primary safety outcome was hospitalization for major bleeding, also assessed in a time-to-event analysis. RESULTS A total of 15,076 patients were followed for a median of 26.2 months (interquartile range [IQR], 19.0 to 34.9). Before randomization, 13,537 (96.0% of those with available information on previous aspirin use) were already taking aspirin, and 85.3% of these patients were previously taking 81 mg of daily aspirin. Death, hospitalization for myocardial infarction, or hospitalization for stroke occurred in 590 patients (estimated percentage, 7.28%) in the 81-mg group and 569 patients (estimated percentage, 7.51%) in the 325-mg group (hazard ratio, 1.02; 95% confidence interval [CI], 0.91 to 1.14). Hospitalization for major bleeding occurred in 53 patients (estimated percentage, 0.63%) in the 81-mg group and 44 patients (estimated percentage, 0.60%) in the 325-mg group (hazard ratio, 1.18; 95% CI, 0.79 to 1.77). Patients assigned to 325 mg had a higher incidence of dose switching than those assigned to 81 mg (41.6% vs. 7.1%) and fewer median days of exposure to the assigned dose (434 days [IQR, 139 to 737] vs. 650 days [IQR, 415 to 922]). CONCLUSIONS In this pragmatic trial involving patients with established cardiovascular disease, there was substantial dose switching to 81 mg of daily aspirin and no significant differences in cardiovascular events or major bleeding between patients assigned to 81 mg and those assigned to 325 mg of aspirin daily.",

author = "Jones, {W. Schuyler} and Hillary Mulder and Wruck, {Lisa M.} and Pencina, {Michael J.} and Sunil Kripalani and Daniel Mu{\~n}oz and Crenshaw, {David L.} and Effron, {Mark B.} and Re, {Richard N.} and Kamal Gupta and {David Anderson}, R. and Pepine, {Carl J.} and Handberg, {Eileen M.} and Manning, {Brittney R.} and Jain, {Sandeep K.} and Saket Girotra and Danielle Riley and DeWalt, {Darren A.} and Jeff Whittle and Goldberg, {Ythan H.} and Roger, {Veronique L.} and Rachel Hess and Benziger, {Catherine P.} and Peter Farrehi and Li Zhou and Ford, {Daniel E.} and Kevin Haynes and VanWormer, {Jeffrey J.} and Knowlton, {Kirk U.} and Kraschnewski, {Jennifer L.} and Polonsky, {Tamar S.} and Fintel, {Dan J.} and Ahmad, {Faraz S.} and McClay, {James C.} and Campbell, {James R.} and Bell, {Douglas S.} and Fonarow, {Gregg C.} and Bradley, {Steven M.} and Anuradha Paranjape and Roe, {Matthew T.} and Robertson, {Holly R.} and Curtis, {Lesley H.} and Sharlow, {Amber G.} and Berdan, {Lisa G.} and Hammill, {Bradley G.} and Harris, {Debra F.} and Qualls, {Laura G.} and Guillaume Marquis-Gravel and Modrow, {Madelaine F.} and Marcus, {Gregory M.} and Carton, {Thomas W.} and Elizabeth Nauman and Waitman, {Lemuel R.} and Kho, {Abel N.} and Shenkman, {Elizabeth A.} and McTigue, {Kathleen M.} and Rainu Kaushal and Masoudi, {Frederick A.} and Antman, {Elliott M.} and Davidson, {Desiree R.} and Kevin Edgley and Merritt, {James G.} and Brown, {Linda S.} and Zemon, {Doris N.} and McCormick, {Thomas E.} and Alikhaani, {Jacqueline D.} and Gregoire, {Kenneth C.} and Rothman, {Russell L.} and Harrington, {Robert A.} and Hernandez, {Adrian F.} and Sandu, {Oana A.}",

note = "Publisher Copyright: Copyright {\textcopyright} 2021 Massachusetts Medical Society.",

year = "2021",

month = may,

day = "27",

doi = "10.1056/NEJMoa2102137",

language = "English (US)",

volume = "384",

pages = "1981--1990",

journal = "New England Journal of Medicine",

issn = "0028-4793",

publisher = "Massachussetts Medical Society",

number = "21",

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TY - JOUR

T1 - Comparative effectiveness of aspirin dosing in cardiovascular disease

AU - Jones, W. Schuyler

AU - Mulder, Hillary

AU - Wruck, Lisa M.

AU - Pencina, Michael J.

AU - Kripalani, Sunil

AU - Muñoz, Daniel

AU - Crenshaw, David L.

AU - Effron, Mark B.

AU - Re, Richard N.

AU - Gupta, Kamal

AU - David Anderson, R.

AU - Pepine, Carl J.

AU - Handberg, Eileen M.

AU - Manning, Brittney R.

AU - Jain, Sandeep K.

AU - Girotra, Saket

AU - Riley, Danielle

AU - DeWalt, Darren A.

AU - Whittle, Jeff

AU - Goldberg, Ythan H.

AU - Roger, Veronique L.

AU - Hess, Rachel

AU - Benziger, Catherine P.

AU - Farrehi, Peter

AU - Zhou, Li

AU - Ford, Daniel E.

AU - Haynes, Kevin

AU - VanWormer, Jeffrey J.

AU - Knowlton, Kirk U.

AU - Kraschnewski, Jennifer L.

AU - Polonsky, Tamar S.

AU - Fintel, Dan J.

AU - Ahmad, Faraz S.

AU - McClay, James C.

AU - Campbell, James R.

AU - Bell, Douglas S.

AU - Fonarow, Gregg C.

AU - Bradley, Steven M.

AU - Paranjape, Anuradha

AU - Roe, Matthew T.

AU - Robertson, Holly R.

AU - Curtis, Lesley H.

AU - Sharlow, Amber G.

AU - Berdan, Lisa G.

AU - Hammill, Bradley G.

AU - Harris, Debra F.

AU - Qualls, Laura G.

AU - Marquis-Gravel, Guillaume

AU - Modrow, Madelaine F.

AU - Marcus, Gregory M.

AU - Carton, Thomas W.

AU - Nauman, Elizabeth

AU - Waitman, Lemuel R.

AU - Kho, Abel N.

AU - Shenkman, Elizabeth A.

AU - McTigue, Kathleen M.

AU - Kaushal, Rainu

AU - Masoudi, Frederick A.

AU - Antman, Elliott M.

AU - Davidson, Desiree R.

AU - Edgley, Kevin

AU - Merritt, James G.

AU - Brown, Linda S.

AU - Zemon, Doris N.

AU - McCormick, Thomas E.

AU - Alikhaani, Jacqueline D.

AU - Gregoire, Kenneth C.

AU - Rothman, Russell L.

AU - Harrington, Robert A.

AU - Hernandez, Adrian F.

AU - Sandu, Oana A.

PY - 2021/5/27

Y1 - 2021/5/27

N2 - The appropriate dose of aspirin to lower the risk of death, myocardial infarction, and stroke and to minimize major bleeding in patients with established atherosclerotic cardiovascular disease is a subject of controversy. METHODS Using an open-label, pragmatic design, we randomly assigned patients with established atherosclerotic cardiovascular disease to a strategy of 81 mg or 325 mg of aspirin per day. The primary effectiveness outcome was a composite of death from any cause, hospitalization for myocardial infarction, or hospitalization for stroke, assessed in a time-to-event analysis. The primary safety outcome was hospitalization for major bleeding, also assessed in a time-to-event analysis. RESULTS A total of 15,076 patients were followed for a median of 26.2 months (interquartile range [IQR], 19.0 to 34.9). Before randomization, 13,537 (96.0% of those with available information on previous aspirin use) were already taking aspirin, and 85.3% of these patients were previously taking 81 mg of daily aspirin. Death, hospitalization for myocardial infarction, or hospitalization for stroke occurred in 590 patients (estimated percentage, 7.28%) in the 81-mg group and 569 patients (estimated percentage, 7.51%) in the 325-mg group (hazard ratio, 1.02; 95% confidence interval [CI], 0.91 to 1.14). Hospitalization for major bleeding occurred in 53 patients (estimated percentage, 0.63%) in the 81-mg group and 44 patients (estimated percentage, 0.60%) in the 325-mg group (hazard ratio, 1.18; 95% CI, 0.79 to 1.77). Patients assigned to 325 mg had a higher incidence of dose switching than those assigned to 81 mg (41.6% vs. 7.1%) and fewer median days of exposure to the assigned dose (434 days [IQR, 139 to 737] vs. 650 days [IQR, 415 to 922]). CONCLUSIONS In this pragmatic trial involving patients with established cardiovascular disease, there was substantial dose switching to 81 mg of daily aspirin and no significant differences in cardiovascular events or major bleeding between patients assigned to 81 mg and those assigned to 325 mg of aspirin daily.

AB - The appropriate dose of aspirin to lower the risk of death, myocardial infarction, and stroke and to minimize major bleeding in patients with established atherosclerotic cardiovascular disease is a subject of controversy. METHODS Using an open-label, pragmatic design, we randomly assigned patients with established atherosclerotic cardiovascular disease to a strategy of 81 mg or 325 mg of aspirin per day. The primary effectiveness outcome was a composite of death from any cause, hospitalization for myocardial infarction, or hospitalization for stroke, assessed in a time-to-event analysis. The primary safety outcome was hospitalization for major bleeding, also assessed in a time-to-event analysis. RESULTS A total of 15,076 patients were followed for a median of 26.2 months (interquartile range [IQR], 19.0 to 34.9). Before randomization, 13,537 (96.0% of those with available information on previous aspirin use) were already taking aspirin, and 85.3% of these patients were previously taking 81 mg of daily aspirin. Death, hospitalization for myocardial infarction, or hospitalization for stroke occurred in 590 patients (estimated percentage, 7.28%) in the 81-mg group and 569 patients (estimated percentage, 7.51%) in the 325-mg group (hazard ratio, 1.02; 95% confidence interval [CI], 0.91 to 1.14). Hospitalization for major bleeding occurred in 53 patients (estimated percentage, 0.63%) in the 81-mg group and 44 patients (estimated percentage, 0.60%) in the 325-mg group (hazard ratio, 1.18; 95% CI, 0.79 to 1.77). Patients assigned to 325 mg had a higher incidence of dose switching than those assigned to 81 mg (41.6% vs. 7.1%) and fewer median days of exposure to the assigned dose (434 days [IQR, 139 to 737] vs. 650 days [IQR, 415 to 922]). CONCLUSIONS In this pragmatic trial involving patients with established cardiovascular disease, there was substantial dose switching to 81 mg of daily aspirin and no significant differences in cardiovascular events or major bleeding between patients assigned to 81 mg and those assigned to 325 mg of aspirin daily.

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U2 - 10.1056/NEJMoa2102137

DO - 10.1056/NEJMoa2102137

M3 - Article

C2 - 33999548

AN - SCOPUS:85106488259

SN - 0028-4793

VL - 384

SP - 1981

EP - 1990

JO - New England Journal of Medicine

JF - New England Journal of Medicine

IS - 21

ER -

Comparative effectiveness of aspirin dosing in cardiovascular disease

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