TY - JOUR
T1 - Antithrombotic Therapy in Patients with Atrial Fibrillation and Acute Coronary Syndrome Treated Medically or with Percutaneous Coronary Intervention or Undergoing Elective Percutaneous Coronary Intervention: Insights from the AUGUSTUS Trial
AU - Windecker, Stephan
AU - Lopes, Renato D.
AU - Massaro, Tyler
AU - Jones-Burton, Charlotte
AU - Granger, Christopher B.
AU - Aronson, Ronald
AU - Heizer, Gretchen
AU - Goodman, Shaun G.
AU - Darius, Harald
AU - Jones, W. Schuyler
AU - Aschermann, Michael
AU - Brieger, David
AU - Cura, Fernando
AU - Engstrøm, Thomas
AU - Fridrich, Viliam
AU - Halvorsen, Sigrun
AU - Huber, Kurt
AU - Kang, Hyun Jae
AU - Leiva-Pons, Jose L.
AU - Lewis, Basil S.
AU - Malaga, German
AU - Meneveau, Nicolas
AU - Merkely, Bela
AU - Milicic, Davor
AU - Morais, Joaõ
AU - Potpara, Tatjana S.
AU - Raev, Dimitar
AU - Sabaté, Manel
AU - De Waha-Thiele, Suzanne
AU - Welsh, Robert C.
AU - Xavier, Denis
AU - Mehran, Roxana
AU - Alexander, John H.
N1 - Funding Information:
The AUGUSTUS study was funded by Bristol-Myers Squibb (Princeton, NJ) and Pfizer, Inc (New York, NY). The study was designed and led by an academic steering committee whose members were responsible for the conduct of the trial. The current analyses were designed by the authors, who were responsible for the collection, analysis, and interpretation of the data; writing of the report; and the decision to submit the article for publication. The corresponding author (R.D.L.) had full access to all the data in the study and had final responsibility for the decision to submit for publication.
Funding Information:
The AUGUSTUS study was funded by Bristol-Myers Squibb (Princeton, NJ) and Pfizer, Inc (New York, NY).
Funding Information:
Dr Windecker reports institutional research and educational grants from Abbott, Amgen, Bayer, BMS, CSL Behring, Boston Scientific, Biotronik, Edwards Lifesciences, Medtronic, Polares, and Sinomed. Dr Lopes reports research grants from Bristol-Myers Squibb, Pfizer, Amgen, Inc, GlaxoSmithKline, Medtronic PLC, and Sanofi Aventis, as well as consulting fees from Bristol-Myers Squibb, Pfizer, Boehringer Ingelheim, and Bayer AG. Dr Jones-Burton is an employee of Bristol-Myers Squibb. Dr Granger reports research grants from Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Jans-sen, Pfizer, Armetheon, AstraZeneca, US Food and Drug Administration, Glaxo-SmithKline, The Medicines Company, Medtronic Foundation, Medtronic Inc, and Novartis, as well as consulting fees from Bayer, Boehringer Ingelheim, Boston Scientific, Bristol-Myers Squibb, Daiichi Sankyo, Janssen, Pfizer, Ab-bvie, Armetheon, AstraZeneca, Eli Lilly, Gilead, GlaxoSmithKline, Hoffmann-La Roche, The Medicines Company, National Institutes of Health, Novartis, Sirtex, Verseon, Apple, Medscape, LLC, Merck, Novo Nordisk, Roche Diagnostics, and Rho Pharmaceuticals. Dr Aronson is an employee of Bristol-Myers Squibb. Dr Goodman reports research grant support and/or speaker/consulting honoraria from Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, CSL Behring, Daiichi-Sankyo, Eli Lilly, Esperion, Fenix Group International, Ferring Pharmaceuticals, GlaxoSmithKline, HLS Therapeutics, Janssen/Johnson & Johnson, Luitpold Pharmaceuticals, Matrizyme, Merck, Novartis, Novo Nordisk A/C, Pfizer, Regeneron, Sanofi, Servier, Tenax Therapeutics, Heart and Stroke Foundation of Ontario/University of Toronto, Canadian Heart Research Centre and MD Primer, Canadian VIGOUR Centre, Duke Clinical Research Institute, and PERFUSE. Dr Darius reports personal fees from Bristol-Myers Squibb/ Pfizer, Boehringer Ingelheim, Bayer Healthcare, and Daiichi Sankyo. Dr Jones reports a research grant from Medtronic PLC and consulting fees from Bayer AG, Bristol-Myers Squibb, and Janssen. Dr Brieger reports travel support and honoraria from Bristol-Myers Squibb/Pfizer. Engstrøm reports personal fees from Bayer AS, Novo, Bristol-Myers Squibb, and Abbott. Dr Halvorsen reports speaker fees from Bayer, Amgen, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Pfizer, Sanofi, and Merck. Dr Huber reports lecture fees from Bristol-Myers Squibb and AstraZeneca. Dr Lewis reports research grants and personal fees from Pfizer and research grants and/or personal fees from Bayer Healthcare MSD, AstraZeneca, KOWA Pharmaceuticals, CSL Behring, and Vifor. Dr Meneveau reports consulting fees, speaker fees, and travel expenses from Bayer Healthcare, Bristol-Myers Squibb/Pfizer, Abbott, Edwards Lifesciences, Terumo, AstraZeneca, and Sanofi Aventis. Dr Morais reports personal fees from Bayer, AstraZeneca, Servier, Novartis, and Boehringer Ingelheim. Dr Potpara has been a consultant for Bayer and has received speaker fees from Pfizer. Dr Raev reports research grants from Bristol-Myers Squibb and Boehringer Ingelheim. Dr Sabaté reports institutional research grants and consulting honoraria from Abbott Vascular. Dr de Waha-Thiele reports consulting fees from Bristol-Myers Squibb. Dr Welsh reports research grants and honoraria from AstraZeneca, Bayer, and Boehringer Ingelheim and honoraria from Bristol-Myers Squibb and Pfizer. Dr Xavier reports institutional research and training grants from AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Cadila Pharma, Eli Lilly, Pfizer, Sanofi, UnitedHealth, and Wellcome Trust, as well as speaker fees from Sanofi and Eli Lilly. Dr Mehran reports institutional research grants from AstraZeneca, Bayer, Beth Israel Deaconess, Bristol-Myers Squibb/Sanofi, CSL Behring, Eli Lilly/Daiichi Sankyo, Medtronic, Novartis, and OrbusNeich; consulting fees from Boston Scientific, Abbott Vascular, Medscape, Siemens Medical Solutions, Roivant Sciences Inc, and Sanofi; consulting (no fees) from Regeneron Pharmaceuticals Inc; institutional consulting fees from Abbott Vascular, Spectranetics/Phillips/Volcano Corporation, Bristol-Myers Squibb, Novartis, and Watermark Research; executive committee member for Janssen Pharmaceuticals and Bristol-Myers Squibb; and <1% equity in Claret Medical and Elixir Medical. Dr Alexander reports research grants from Bristol-Myers Squibb, Boehringer Ingelheim, AstraZeneca, CryoLife, CSL Behring, US Food and Drug Administration, National Institutes of Health, Sanofi, and VoluMe-trix, as well as consulting fees from Pfizer, Bristol-Myers Squibb, AbbVie Pharmaceuticals, CSL Behring, Novo Nordisk, Portola Pharmaceuticals, Quantum Genomics, Teikoku Pharmaceuticals, VA Cooperative Studies, and Zafgen. The other authors report no conflicts.
Publisher Copyright:
© 2019 American Heart Association, Inc.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2019/12/3
Y1 - 2019/12/3
N2 - Background: The safety and efficacy of antithrombotic regimens may differ between patients with atrial fibrillation who have acute coronary syndromes (ACS), treated medically or with percutaneous coronary intervention (PCI), and those undergoing elective PCI. Methods: Using a 2×2 factorial design, we compared apixaban with vitamin K antagonists and aspirin with placebo in patients with atrial fibrillation who had ACS or were undergoing PCI and were receiving a P2Y12 inhibitor. We explored bleeding, death and hospitalization, as well as death and ischemic events, by antithrombotic strategy in 3 prespecified subgroups: Patients with ACS treated medically, patients with ACS treated with PCI, and those undergoing elective PCI. Results: Of 4614 patients enrolled, 1097 (23.9%) had ACS treated medically, 1714 (37.3%) had ACS treated with PCI, and 1784 (38.8%) had elective PCI. Apixaban compared with vitamin K antagonist reduced International Society on Thrombosis and Haemostasis major or clinically relevant nonmajor bleeding in patients with ACS treated medically (hazard ratio [HR], 0.44 [95% CI, 0.28-0.68]), patients with ACS treated with PCI (HR, 0.68 [95% CI, 0.52-0.89]), and patients undergoing elective PCI (HR, 0.82 [95% CI, 0.64-1.04]; Pinteraction=0.052) and reduced death or hospitalization in the ACS treated medically (HR, 0.71 [95% CI, 0.54-0.92]), ACS treated with PCI (HR, 0.88 [95% CI, 0.74-1.06]), and elective PCI (HR, 0.87 [95% CI, 0.72-1.04]; Pinteraction=0.345) groups. Compared with vitamin K antagonists, apixaban resulted in a similar effect on death and ischemic events in the ACS treated medically, ACS treated with PCI, and elective PCI groups (Pinteraction=0.356). Aspirin had a higher rate of bleeding than did placebo in patients with ACS treated medically (HR, 1.49 [95% CI, 0.98-2.26]), those with ACS treated with PCI (HR, 2.02 [95% CI, 1.53-2.67]), and those undergoing elective PCI (HR, 1.91 [95% CI, 1.48-2.47]; Pinteraction=0.479). For the same comparison, there was no difference in outcomes among the 3 groups for the composite of death or hospitalization (Pinteraction=0.787) and death and ischemic events (Pinteraction=0.710). Conclusions: An antithrombotic regimen consisting of apixaban and a P2Y12 inhibitor without aspirin provides superior safety and similar efficacy in patients with atrial fibrillation who have ACS, whether managed medically or with PCI, and those undergoing elective PCI compared with regimens that include vitamin K antagonists, aspirin, or both.
AB - Background: The safety and efficacy of antithrombotic regimens may differ between patients with atrial fibrillation who have acute coronary syndromes (ACS), treated medically or with percutaneous coronary intervention (PCI), and those undergoing elective PCI. Methods: Using a 2×2 factorial design, we compared apixaban with vitamin K antagonists and aspirin with placebo in patients with atrial fibrillation who had ACS or were undergoing PCI and were receiving a P2Y12 inhibitor. We explored bleeding, death and hospitalization, as well as death and ischemic events, by antithrombotic strategy in 3 prespecified subgroups: Patients with ACS treated medically, patients with ACS treated with PCI, and those undergoing elective PCI. Results: Of 4614 patients enrolled, 1097 (23.9%) had ACS treated medically, 1714 (37.3%) had ACS treated with PCI, and 1784 (38.8%) had elective PCI. Apixaban compared with vitamin K antagonist reduced International Society on Thrombosis and Haemostasis major or clinically relevant nonmajor bleeding in patients with ACS treated medically (hazard ratio [HR], 0.44 [95% CI, 0.28-0.68]), patients with ACS treated with PCI (HR, 0.68 [95% CI, 0.52-0.89]), and patients undergoing elective PCI (HR, 0.82 [95% CI, 0.64-1.04]; Pinteraction=0.052) and reduced death or hospitalization in the ACS treated medically (HR, 0.71 [95% CI, 0.54-0.92]), ACS treated with PCI (HR, 0.88 [95% CI, 0.74-1.06]), and elective PCI (HR, 0.87 [95% CI, 0.72-1.04]; Pinteraction=0.345) groups. Compared with vitamin K antagonists, apixaban resulted in a similar effect on death and ischemic events in the ACS treated medically, ACS treated with PCI, and elective PCI groups (Pinteraction=0.356). Aspirin had a higher rate of bleeding than did placebo in patients with ACS treated medically (HR, 1.49 [95% CI, 0.98-2.26]), those with ACS treated with PCI (HR, 2.02 [95% CI, 1.53-2.67]), and those undergoing elective PCI (HR, 1.91 [95% CI, 1.48-2.47]; Pinteraction=0.479). For the same comparison, there was no difference in outcomes among the 3 groups for the composite of death or hospitalization (Pinteraction=0.787) and death and ischemic events (Pinteraction=0.710). Conclusions: An antithrombotic regimen consisting of apixaban and a P2Y12 inhibitor without aspirin provides superior safety and similar efficacy in patients with atrial fibrillation who have ACS, whether managed medically or with PCI, and those undergoing elective PCI compared with regimens that include vitamin K antagonists, aspirin, or both.
UR - http://www.scopus.com/inward/record.url?scp=85075526111&partnerID=8YFLogxK
U2 - 10.1161/CIRCULATIONAHA.119.043308
DO - 10.1161/CIRCULATIONAHA.119.043308
M3 - Journal articles
C2 - 31557056
AN - SCOPUS:85075526111
SN - 0009-7322
VL - 140
SP - 1921
EP - 1932
JO - Circulation
JF - Circulation
IS - 23
ER -
