TY - JOUR
T1 - Anticoagulation with or without Clopidogrel after Transcatheter Aortic-Valve Implantation
AU - Nijenhuis, V. J.
AU - Brouwer, J.
AU - Delewi, R.
AU - Hermanides, R. S.
AU - Holvoet, W.
AU - Dubois, C. L. F.
AU - Frambach, P.
AU - De Bruyne, B.
AU - van Houwelingen, G. K.
AU - Van der Heyden, J. A. S.
AU - Tousek, P.
AU - van der Kley, F.
AU - Buysschaert, I.
AU - Schotborgh, C. E.
AU - Ferdinande, B.
AU - van der Harst, P.
AU - Roosen, J.
AU - Peper, J.
AU - Thielen, F. W. F.
AU - Veenstra, L.
AU - Yin, D. R. P. P. Chan Pin
AU - Swaans, M. J.
AU - Rensing, B. J. W. M.
AU - van 't Hof, A. W. J.
AU - Timmers, L.
AU - Kelder, J. C.
AU - Stella, P. R.
AU - Baan, J.
AU - ten Berg, J. M.
N1 - Funding Information:
Supported by the Netherlands Organization for Health Research and Development. Dr. Delewi reports receiving lecture fees from Bayer; Dr. De Bruyne, receiving grant support, paid to his institution, from Abbott Vascular and Biotronik, receiving grant support and consulting fees, paid to his institution, from Boston Scientific, receiving consulting fees, paid to his institution, from Opsens, and being a shareholder in Siemens, GE, Bayer, Philips Healthcare, HeartFlow, Edwards Lifesciences, and Ceylad; Dr. Swaans, receiving consulting fees and lecture fees from Abbott Vascular, Boston Scientific, Philips Healthcare, and BioVentrix; Dr. van ’t Hof, receiving grant support from Medtronic and Abbott Vas- cular and grant support and lecture fees from AstraZeneca; and Dr. Baan, receiving grant support from Edwards Lifesciences. No other potential conflict of interest relevant to this article was reported.
Publisher Copyright:
Copyright © 2020 Massachusetts Medical Society.
PY - 2020/4/30
Y1 - 2020/4/30
N2 - In a trial comparing the addition of clopidogrel with no clopidogrel in patients receiving anticoagulation, the incidence of any bleeding and of non-procedure-related bleeding was lower in the monotherapy group. Composite cardiovascular outcomes were noninferior for the monotherapy group but were superior only for a composite that included bleeding.Background The roles of anticoagulation alone or with an antiplatelet agent after transcatheter aortic-valve implantation (TAVI) have not been well studied.Methods We performed a randomized trial of clopidogrel in patients undergoing TAVI who were receiving oral anticoagulation for appropriate indications. Patients were assigned before TAVI in a 1:1 ratio not to receive clopidogrel or to receive clopidogrel for 3 months. The two primary outcomes were all bleeding and non-procedure-related bleeding over a period of 12 months. Procedure-related bleeding was defined as Bleeding Academic Research Consortium type 4 severe bleeding, and therefore most bleeding at the puncture site was counted as non-procedure-related. The two secondary outcomes were a composite of death from cardiovascular causes, non-procedure-related bleeding, stroke, or myocardial infarction at 12 months (secondary composite 1) and a composite of death from cardiovascular causes, ischemic stroke, or myocardial infarction (secondary composite 2), both tested for noninferiority (noninferiority margin, 7.5 percentage points) and superiority.Results Bleeding occurred in 34 of the 157 patients (21.7%) receiving oral anticoagulation alone and in 54 of the 156 (34.6%) receiving oral anticoagulation plus clopidogrel (risk ratio, 0.63; 95% confidence interval [CI], 0.43 to 0.90; P=0.01); most bleeding events were at the TAVI access site. Non-procedure-related bleeding occurred in 34 patients (21.7%) and in 53 (34.0%), respectively (risk ratio, 0.64; 95% CI, 0.44 to 0.92; P=0.02). Most bleeding occurred in the first month and was minor. A secondary composite 1 event occurred in 49 patients (31.2%) receiving oral anticoagulation alone and in 71 (45.5%) receiving oral anticoagulation plus clopidogrel (difference, -14.3 percentage points; 95% CI for noninferiority, -25.0 to -3.6; risk ratio, 0.69; 95% CI for superiority, 0.51 to 0.92). A secondary composite 2 event occurred in 21 patients (13.4%) and in 27 (17.3%), respectively (difference, -3.9 percentage points; 95% CI for noninferiority, -11.9 to 4.0; risk ratio, 0.77; 95% CI for superiority, 0.46 to 1.31).Conclusions In patients undergoing TAVI who were receiving oral anticoagulation, the incidence of serious bleeding over a period of 1 month or 1 year was lower with oral anticoagulation alone than with oral anticoagulation plus clopidogrel. (Funded by the Netherlands Organization for Health Research and Development; POPular TAVI EU Clinical Trials Register number, ; ClinicalTrials.gov number, .)
AB - In a trial comparing the addition of clopidogrel with no clopidogrel in patients receiving anticoagulation, the incidence of any bleeding and of non-procedure-related bleeding was lower in the monotherapy group. Composite cardiovascular outcomes were noninferior for the monotherapy group but were superior only for a composite that included bleeding.Background The roles of anticoagulation alone or with an antiplatelet agent after transcatheter aortic-valve implantation (TAVI) have not been well studied.Methods We performed a randomized trial of clopidogrel in patients undergoing TAVI who were receiving oral anticoagulation for appropriate indications. Patients were assigned before TAVI in a 1:1 ratio not to receive clopidogrel or to receive clopidogrel for 3 months. The two primary outcomes were all bleeding and non-procedure-related bleeding over a period of 12 months. Procedure-related bleeding was defined as Bleeding Academic Research Consortium type 4 severe bleeding, and therefore most bleeding at the puncture site was counted as non-procedure-related. The two secondary outcomes were a composite of death from cardiovascular causes, non-procedure-related bleeding, stroke, or myocardial infarction at 12 months (secondary composite 1) and a composite of death from cardiovascular causes, ischemic stroke, or myocardial infarction (secondary composite 2), both tested for noninferiority (noninferiority margin, 7.5 percentage points) and superiority.Results Bleeding occurred in 34 of the 157 patients (21.7%) receiving oral anticoagulation alone and in 54 of the 156 (34.6%) receiving oral anticoagulation plus clopidogrel (risk ratio, 0.63; 95% confidence interval [CI], 0.43 to 0.90; P=0.01); most bleeding events were at the TAVI access site. Non-procedure-related bleeding occurred in 34 patients (21.7%) and in 53 (34.0%), respectively (risk ratio, 0.64; 95% CI, 0.44 to 0.92; P=0.02). Most bleeding occurred in the first month and was minor. A secondary composite 1 event occurred in 49 patients (31.2%) receiving oral anticoagulation alone and in 71 (45.5%) receiving oral anticoagulation plus clopidogrel (difference, -14.3 percentage points; 95% CI for noninferiority, -25.0 to -3.6; risk ratio, 0.69; 95% CI for superiority, 0.51 to 0.92). A secondary composite 2 event occurred in 21 patients (13.4%) and in 27 (17.3%), respectively (difference, -3.9 percentage points; 95% CI for noninferiority, -11.9 to 4.0; risk ratio, 0.77; 95% CI for superiority, 0.46 to 1.31).Conclusions In patients undergoing TAVI who were receiving oral anticoagulation, the incidence of serious bleeding over a period of 1 month or 1 year was lower with oral anticoagulation alone than with oral anticoagulation plus clopidogrel. (Funded by the Netherlands Organization for Health Research and Development; POPular TAVI EU Clinical Trials Register number, ; ClinicalTrials.gov number, .)
KW - ATRIAL-FIBRILLATION
KW - ANTIPLATELET THERAPY
KW - 1-YEAR OUTCOMES
KW - REPLACEMENT
KW - RISK
KW - TAVI
KW - MANAGEMENT
KW - DEFINITIONS
KW - GUIDELINES
KW - PREDICTORS
U2 - 10.1056/nejmoa1915152
DO - 10.1056/nejmoa1915152
M3 - Article
C2 - 32223116
SN - 0028-4793
VL - 382
SP - 1696
EP - 1707
JO - New England Journal of Medicine
JF - New England Journal of Medicine
IS - 18
ER -