Comparative Effectiveness of Aspirin Dosing in Cardiovascular Disease.
Aged
Aspirin
/ administration & dosage
Atherosclerosis
/ drug therapy
Cardiovascular Diseases
/ drug therapy
Female
Hemorrhage
/ chemically induced
Hospitalization
Humans
Male
Medication Adherence
/ statistics & numerical data
Middle Aged
Myocardial Infarction
/ epidemiology
Platelet Aggregation Inhibitors
/ administration & dosage
Secondary Prevention
Stroke
/ epidemiology
Journal
The New England journal of medicine
ISSN: 1533-4406
Titre abrégé: N Engl J Med
Pays: United States
ID NLM: 0255562
Informations de publication
Date de publication:
27 05 2021
27 05 2021
Historique:
pubmed:
18
5
2021
medline:
11
6
2021
entrez:
17
5
2021
Statut:
ppublish
Résumé
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. 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. 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]). 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. (Funded by the Patient-Centered Outcomes Research Institute; ADAPTABLE ClinicalTrials.gov number, NCT02697916.).
Sections du résumé
BACKGROUND
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. (Funded by the Patient-Centered Outcomes Research Institute; ADAPTABLE ClinicalTrials.gov number, NCT02697916.).
Identifiants
pubmed: 33999548
doi: 10.1056/NEJMoa2102137
pmc: PMC9908069
mid: NIHMS1864598
doi:
Substances chimiques
Platelet Aggregation Inhibitors
0
Aspirin
R16CO5Y76E
Banques de données
ClinicalTrials.gov
['NCT02697916']
Types de publication
Comparative Study
Journal Article
Multicenter Study
Pragmatic Clinical Trial
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1981-1990Subventions
Organisme : AHRQ HHS
ID : K12 HS026385
Pays : United States
Organisme : NHLBI NIH HHS
ID : K23 HL155970
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001422
Pays : United States
Organisme : Patient-Centered Outcomes Research Institute
ID : Award (ASP-1502-27029)
Pays : United States
Investigateurs
Robert A Harrington
(RA)
Russell Rothman
(R)
Adrian F Hernandez
(AF)
W Schuyler Jones
(WS)
Lesley H Curtis
(LH)
Greg Marcus
(G)
Henry Cruz
(H)
Patient Partner
(P)
Jacqueline Alikhaani
(J)
Matthew Roe
(M)
Lisa Berdan
(L)
Holly Robertson
(H)
Amber Sharlow
(A)
Brad Hammill
(B)
Debra Harris
(D)
Laura Qualls
(L)
Hillary Mulder
(H)
Lisa Wruck
(L)
Michael Pencina
(M)
Guillaume Marquis-Gravel
(G)
Clyde Yancy
(C)
Dave Demets
(D)
Judith Hochman
(J)
Bernard Gersh
(B)
Alice Jacobs
(A)
Debbe McCall
(D)
Hugo Campos
(H)
Desiree Davidson
(D)
Kevin Edgley
(K)
Greg Merritt
(G)
Linda Brown
(L)
Henry Cruz
(H)
Nadine Zemon
(N)
Tom McCormick
(T)
Ken Gregoire
(K)
Abel Kho
(A)
Russ Waitman
(R)
Veronique Roger
(V)
Rainu Kaushal
(R)
Elizabeth Shenkman
(E)
Kathleen McTigue
(K)
Douglas Bell
(D)
Thomas Carton
(T)
A Kho
(A)
M Nodal
(M)
D Fintel
(D)
F Ahmad
(F)
A Williams
(A)
R C Shah
(RC)
A Flores
(A)
M Jansen
(M)
T Polonsky
(T)
D Hood
(D)
J French
(J)
P Dexter
(P)
D Riley
(D)
N Smith
(N)
S Girotra
(S)
R Waitman
(R)
S Chandaka
(S)
T McMahon
(T)
K Greening
(K)
Y Murr
(Y)
K Munshi
(K)
H Sandoval
(H)
K Gupta
(K)
L Verhagen
(L)
T Foss
(T)
J VanWormer
(J)
K Osinski
(K)
A Schwarz
(A)
S Cornell
(S)
M Berendt
(M)
J Whittle
(J)
A Mosa
(A)
V Mandhadi
(V)
L Lawrence
(L)
A Kumar
(A)
D Mehr
(D)
J McClay
(J)
P Guda
(P)
A Wolfe
(A)
C Geary
(C)
K Ostlund
(K)
L Larson
(L)
R Harper
(R)
J Campbell
(J)
L Manuel
(L)
O Suarez
(O)
J Polanco
(J)
A Tirado-Ramos
(A)
S Tsai
(S)
J Cai
(J)
M Bell
(M)
P Reeder
(P)
T Bosler
(T)
K Wilkinson
(K)
S Antony
(S)
S Das
(S)
K Hanson
(K)
C Rodgers
(C)
E Ebere
(E)
S Bradley
(S)
M Miedema
(M)
R Thiel
(R)
B Lemke
(B)
I Haller
(I)
C Benziger
(C)
S Rea
(S)
D Ward
(D)
H Maestas
(H)
N Garbe
(N)
L Evans
(L)
P Haug
(P)
K Knowlton
(K)
V Roger
(V)
E Koepsell
(E)
S Brue
(S)
J Bauman
(J)
B Bucknell
(B)
H Jouni
(H)
M Jindra
(M)
J Harper
(J)
M Bright
(M)
B Lampert
(B)
S Fernandez
(S)
J Ryan
(J)
S Brougher
(S)
M Harris
(M)
A Fishstom
(A)
L Ferguson
(L)
D Braswell
(D)
K Shah
(K)
B Nallamothu
(B)
C Friedman
(C)
D Williams
(D)
P Farrehi
(P)
W S Jones
(WS)
J Curtis
(J)
J Hamill
(J)
B O'Brien
(B)
M B Summers
(MB)
X Idriss
(X)
W Pohlman
(W)
K Thompson
(K)
D Dewalt
(D)
R Bradford
(R)
T Barber
(T)
D Crenshaw
(D)
K Goggins
(K)
W Hucke
(W)
S Kripalani
(S)
S McCrate
(S)
J Moore
(J)
D Muñoz
(D)
C O'Donnell
(C)
C Pritchett
(C)
C Roumie
(C)
R Servis
(R)
K Worley
(K)
J Borgman
(J)
L Doomy
(L)
K Blinson
(K)
G Rosenthal
(G)
L Zhou
(L)
O A Sandu
(OA)
Y Goldberg
(Y)
E Fass
(E)
D McKee
(D)
J Lin
(J)
C Pulgarin
(C)
S Blecker
(S)
R Kaushal
(R)
A Cohen
(A)
N Goldberg
(N)
S Chaudhary
(S)
A LaMar
(A)
T Haque
(T)
K LaScalea
(K)
R Kim
(R)
T Campion
(T)
B Shenkman
(B)
B Roth
(B)
D Bright
(D)
J Hensley
(J)
T Chou
(T)
J-A Norton
(JA)
C Garrett
(C)
C Pepine
(C)
D Anderson
(D)
E Handberg
(E)
B Johnson
(B)
T Robinson
(T)
D Allen
(D)
M Warrington
(M)
H Seifein
(H)
H Noel
(H)
V K Kasi
(VK)
D Gumas
(D)
H Lehmann
(H)
M Gauvey-Kern
(M)
D Ford
(D)
T Metkus
(T)
J McCullough
(J)
K Confer
(K)
C Chuang
(C)
J Kraschnewski
(J)
M Weiner
(M)
J Turella
(J)
A Paranjape
(A)
K McTigue
(K)
N Cappella
(N)
P Kant
(P)
A Arita
(A)
E Klawson
(E)
S Jain
(S)
A Huffman
(A)
C Moynier
(C)
T Greimes
(T)
B Steinberg
(B)
R Hess
(R)
M Zachariah
(M)
D Bell
(D)
G Fonarow
(G)
T Carton
(T)
B Nauman
(B)
L Rudov
(L)
L Hall
(L)
L Clariday
(L)
R Baker
(R)
P McCullough
(P)
C Parke
(C)
D Rachal
(D)
R Jenkins
(R)
S Cohen
(S)
G Liu
(G)
M Effron
(M)
R Re
(R)
A Irimpen
(A)
M Pletcher
(M)
M Faulkner
(M)
M Cziraky
(M)
Q Shi
(Q)
A Marshall
(A)
E R Kennedy
(ER)
K Haynes
(K)
V Nair
(V)
Commentaires et corrections
Type : CommentIn
Type : CommentIn
Type : CommentIn
Type : CommentIn
Type : CommentIn
Type : CommentIn
Type : CommentIn
Informations de copyright
Copyright © 2021 Massachusetts Medical Society.
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