Aspirin with or without clopidogrel after transcatheter aortic-valve implantation

J. Brouwer; V. J. Nijenhuis; R. Delewi; R. S. Hermanides; W. Holvoet; C. L.F. Dubois; P. Frambach; B. de Bruyne; G. K. van Houwelingen; J. A.S. van der Heyden; P. Toušek; F. van der Kley; I. Buysschaert; C. E. Schotborgh; B. Ferdinande; P. van der Harst; J. Roosen; J. Peper; F. W.F. Thielen; L. Veenstra; D. R.P.P. Chan Pin Yin; M. J. Swaans; B. J.W.M. Rensing; A. W.J. van't Hof; L. Timmers; J. C. Kelder; P. R. Stella; J. Baan; J. M. ten Berg

doi:10.1056/NEJMoa2017815

Aspirin with or without clopidogrel after transcatheter aortic-valve implantation

J. Brouwer, V. J. Nijenhuis, R. Delewi, R. S. Hermanides, W. Holvoet, C. L.F. Dubois, P. Frambach, B. de Bruyne, G. K. van Houwelingen, J. A.S. van der Heyden, P. Toušek, F. van der Kley, I. Buysschaert, C. E. Schotborgh, B. Ferdinande, P. van der Harst, J. Roosen, J. Peper, F. W.F. Thielen, L. VeenstraD. R.P.P. Chan Pin Yin, M. J. Swaans, B. J.W.M. Rensing, A. W.J. van't Hof, L. Timmers, J. C. Kelder, P. R. Stella, J. Baan, J. M. ten Berg^*

^*Corresponding author for this work

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

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Abstract

BACKGROUND The effect of single as compared with dual antiplatelet treatment on bleeding and thromboembolic events after transcatheter aortic-valve implantation (TAVI) in patients who do not have an indication for long-term anticoagulation has not been well studied. METHODS In a randomized, controlled trial, we assigned a subgroup of patients who were undergoing TAVI and did not have an indication for long-term anticoagulation, in a 1:1 ratio, to receive aspirin alone or aspirin plus clopidogrel for 3 months. The two primary outcomes were all bleeding (including minor, major, and life-threatening or disabling bleeding) and non-procedure-related bleeding over a period of 12 months. Most bleeding at the TAVI 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 (secondary composite 1) and a composite of death from cardiovascular causes, ischemic stroke, or myocardial infarction (secondary composite 2) at 1 year, with both outcomes tested sequentially for noninferiority (noninferiority margin, 7.5 percentage points) and superiority. RESULTS A total of 331 patients were assigned to receive aspirin alone and 334 were assigned to receive aspirin plus clopidogrel. A bleeding event occurred in 50 patients (15.1%) receiving aspirin alone and in 89 (26.6%) receiving aspirin plus clopidogrel (risk ratio, 0.57; 95% confidence interval [CI], 0.42 to 0.77; P=0.001). Non-procedure-related bleeding occurred in 50 patients (15.1%) and 83 patients (24.9%), respectively (risk ratio, 0.61; 95% CI, 0.44 to 0.83; P=0.005). A secondary composite 1 event occurred in 76 patients (23.0%) receiving aspirin alone and in 104 (31.1%) receiving aspirin plus clopidogrel (difference, −8.2 percentage points; 95% CI for noninferiority, −14.9 to −1.5; P<0.001; risk ratio, 0.74; 95% CI for superiority, 0.57 to 0.95; P=0.04). A secondary composite 2 event occurred in 32 patients (9.7%) and 33 patients (9.9%), respectively (difference, −0.2 percentage points; 95% CI for noninferiority, −4.7 to 4.3; P=0.004; risk ratio, 0.98; 95% CI for superiority, 0.62 to 1.55; P=0.93). A total of 44 patients (13.3%) and 32 (9.6%), respectively, received oral anticoagulation during the trial. CONCLUSIONS Among patients undergoing TAVI who did not have an indication for oral anticoagulation, the incidence of bleeding and the composite of bleeding or thromboembolic events at 1 year were significantly less frequent with aspirin than with aspirin plus clopidogrel administered for 3 months.

Original language	English
Pages (from-to)	1447-1457
Number of pages	11
Journal	New England Journal of Medicine
Volume	383
Issue number	15
DOIs	https://doi.org/10.1056/NEJMoa2017815
Publication status	Published - 8 Oct 2020

Bibliographical note

Funding Information:
Dr. Dubois reports receiving consulting fees from Boston Scientific and Edwards Lifesciences; Dr. De Bruyne, receiving grant support and consulting fees, paid to Cardiovascular Center Aalst, from Abbott Vascular and Boston Scientific, receiving grant support, paid to Cardiovascular Center Aalst, from Bio-tronik, owning stock in Edwards Lifesciences, General Electric, Philips, and Siemens, and owning stock options in HeartFlow; Dr. Swaans, receiving consulting fees and lecture fees from Abbott Vascular, BioVentrix, Boston Scientific, and Philips Healthcare; Dr. van ’t Hof, receiving grant support, paid to Stichting Perfusie, from Abbott Pharmaceuticals, grant support, paid to Isala Academy, from AstraZeneca, and grant support, paid to the Cardiovascular Research Institute Maastricht, from Medtronic; and Dr. ten Berg, receiving grant support, paid to St. Antonius Hospital, and lecture fees from AstraZeneca, travel support from Bayer, and lecture fees from Boehringer Ingelheim and Pfizer. No other potential conflict of interest relevant to this article was reported.

Funding Information:
Supported by the Netherlands Organization for Health Research and Development.

Publisher Copyright:
© 2020 Massachusetts Medical Society.

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Aspirin with or without ClopidogrelAccepted author manuscript, 622 KBLicence: Article 25fa Dutch Copyright Act

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Brouwer, J., Nijenhuis, V. J., Delewi, R., Hermanides, R. S., Holvoet, W., Dubois, C. L. F., Frambach, P., de Bruyne, B., van Houwelingen, G. K., van der Heyden, J. A. S., Toušek, P., van der Kley, F., Buysschaert, I., Schotborgh, C. E., Ferdinande, B., van der Harst, P., Roosen, J., Peper, J., Thielen, F. W. F., ... ten Berg, J. M. (2020). Aspirin with or without clopidogrel after transcatheter aortic-valve implantation. New England Journal of Medicine, 383(15), 1447-1457. https://doi.org/10.1056/NEJMoa2017815

@article{510a66ecd35e432095a26aef323efeb9,

title = "Aspirin with or without clopidogrel after transcatheter aortic-valve implantation",

abstract = "BACKGROUND The effect of single as compared with dual antiplatelet treatment on bleeding and thromboembolic events after transcatheter aortic-valve implantation (TAVI) in patients who do not have an indication for long-term anticoagulation has not been well studied. METHODS In a randomized, controlled trial, we assigned a subgroup of patients who were undergoing TAVI and did not have an indication for long-term anticoagulation, in a 1:1 ratio, to receive aspirin alone or aspirin plus clopidogrel for 3 months. The two primary outcomes were all bleeding (including minor, major, and life-threatening or disabling bleeding) and non-procedure-related bleeding over a period of 12 months. Most bleeding at the TAVI 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 (secondary composite 1) and a composite of death from cardiovascular causes, ischemic stroke, or myocardial infarction (secondary composite 2) at 1 year, with both outcomes tested sequentially for noninferiority (noninferiority margin, 7.5 percentage points) and superiority. RESULTS A total of 331 patients were assigned to receive aspirin alone and 334 were assigned to receive aspirin plus clopidogrel. A bleeding event occurred in 50 patients (15.1%) receiving aspirin alone and in 89 (26.6%) receiving aspirin plus clopidogrel (risk ratio, 0.57; 95% confidence interval [CI], 0.42 to 0.77; P=0.001). Non-procedure-related bleeding occurred in 50 patients (15.1%) and 83 patients (24.9%), respectively (risk ratio, 0.61; 95% CI, 0.44 to 0.83; P=0.005). A secondary composite 1 event occurred in 76 patients (23.0%) receiving aspirin alone and in 104 (31.1%) receiving aspirin plus clopidogrel (difference, −8.2 percentage points; 95% CI for noninferiority, −14.9 to −1.5; P<0.001; risk ratio, 0.74; 95% CI for superiority, 0.57 to 0.95; P=0.04). A secondary composite 2 event occurred in 32 patients (9.7%) and 33 patients (9.9%), respectively (difference, −0.2 percentage points; 95% CI for noninferiority, −4.7 to 4.3; P=0.004; risk ratio, 0.98; 95% CI for superiority, 0.62 to 1.55; P=0.93). A total of 44 patients (13.3%) and 32 (9.6%), respectively, received oral anticoagulation during the trial. CONCLUSIONS Among patients undergoing TAVI who did not have an indication for oral anticoagulation, the incidence of bleeding and the composite of bleeding or thromboembolic events at 1 year were significantly less frequent with aspirin than with aspirin plus clopidogrel administered for 3 months.",

author = "J. Brouwer and Nijenhuis, {V. J.} and R. Delewi and Hermanides, {R. S.} and W. Holvoet and Dubois, {C. L.F.} and P. Frambach and {de Bruyne}, B. and {van Houwelingen}, {G. K.} and {van der Heyden}, {J. A.S.} and P. Tou{\v s}ek and {van der Kley}, F. and I. Buysschaert and Schotborgh, {C. E.} and B. Ferdinande and {van der Harst}, P. and J. Roosen and J. Peper and Thielen, {F. W.F.} and L. Veenstra and {Chan Pin Yin}, {D. R.P.P.} and Swaans, {M. J.} and Rensing, {B. J.W.M.} and {van't Hof}, {A. W.J.} and L. Timmers and Kelder, {J. C.} and Stella, {P. R.} and J. Baan and {ten Berg}, {J. M.}",

note = "Funding Information: Dr. Dubois reports receiving consulting fees from Boston Scientific and Edwards Lifesciences; Dr. De Bruyne, receiving grant support and consulting fees, paid to Cardiovascular Center Aalst, from Abbott Vascular and Boston Scientific, receiving grant support, paid to Cardiovascular Center Aalst, from Bio-tronik, owning stock in Edwards Lifesciences, General Electric, Philips, and Siemens, and owning stock options in HeartFlow; Dr. Swaans, receiving consulting fees and lecture fees from Abbott Vascular, BioVentrix, Boston Scientific, and Philips Healthcare; Dr. van {\textquoteright}t Hof, receiving grant support, paid to Stichting Perfusie, from Abbott Pharmaceuticals, grant support, paid to Isala Academy, from AstraZeneca, and grant support, paid to the Cardiovascular Research Institute Maastricht, from Medtronic; and Dr. ten Berg, receiving grant support, paid to St. Antonius Hospital, and lecture fees from AstraZeneca, travel support from Bayer, and lecture fees from Boehringer Ingelheim and Pfizer. No other potential conflict of interest relevant to this article was reported. Funding Information: Supported by the Netherlands Organization for Health Research and Development. Publisher Copyright: {\textcopyright} 2020 Massachusetts Medical Society.",

year = "2020",

month = oct,

day = "8",

doi = "10.1056/NEJMoa2017815",

language = "English",

volume = "383",

pages = "1447--1457",

journal = "New England Journal of Medicine",

issn = "0028-4793",

publisher = "Massachussetts Medical Society",

number = "15",

}

Brouwer, J, Nijenhuis, VJ, Delewi, R, Hermanides, RS, Holvoet, W, Dubois, CLF, Frambach, P, de Bruyne, B, van Houwelingen, GK, van der Heyden, JAS, Toušek, P, van der Kley, F, Buysschaert, I, Schotborgh, CE, Ferdinande, B, van der Harst, P, Roosen, J, Peper, J, Thielen, FWF, Veenstra, L, Chan Pin Yin, DRPP, Swaans, MJ, Rensing, BJWM, van't Hof, AWJ, Timmers, L, Kelder, JC, Stella, PR, Baan, J & ten Berg, JM 2020, 'Aspirin with or without clopidogrel after transcatheter aortic-valve implantation', New England Journal of Medicine, vol. 383, no. 15, pp. 1447-1457. https://doi.org/10.1056/NEJMoa2017815

TY - JOUR

T1 - Aspirin with or without clopidogrel after transcatheter aortic-valve implantation

AU - Brouwer, J.

AU - Nijenhuis, V. 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 - Toušek, 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 - Chan Pin Yin, D. R.P.P.

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: Dr. Dubois reports receiving consulting fees from Boston Scientific and Edwards Lifesciences; Dr. De Bruyne, receiving grant support and consulting fees, paid to Cardiovascular Center Aalst, from Abbott Vascular and Boston Scientific, receiving grant support, paid to Cardiovascular Center Aalst, from Bio-tronik, owning stock in Edwards Lifesciences, General Electric, Philips, and Siemens, and owning stock options in HeartFlow; Dr. Swaans, receiving consulting fees and lecture fees from Abbott Vascular, BioVentrix, Boston Scientific, and Philips Healthcare; Dr. van ’t Hof, receiving grant support, paid to Stichting Perfusie, from Abbott Pharmaceuticals, grant support, paid to Isala Academy, from AstraZeneca, and grant support, paid to the Cardiovascular Research Institute Maastricht, from Medtronic; and Dr. ten Berg, receiving grant support, paid to St. Antonius Hospital, and lecture fees from AstraZeneca, travel support from Bayer, and lecture fees from Boehringer Ingelheim and Pfizer. No other potential conflict of interest relevant to this article was reported. Funding Information: Supported by the Netherlands Organization for Health Research and Development. Publisher Copyright: © 2020 Massachusetts Medical Society.

PY - 2020/10/8

Y1 - 2020/10/8

N2 - BACKGROUND The effect of single as compared with dual antiplatelet treatment on bleeding and thromboembolic events after transcatheter aortic-valve implantation (TAVI) in patients who do not have an indication for long-term anticoagulation has not been well studied. METHODS In a randomized, controlled trial, we assigned a subgroup of patients who were undergoing TAVI and did not have an indication for long-term anticoagulation, in a 1:1 ratio, to receive aspirin alone or aspirin plus clopidogrel for 3 months. The two primary outcomes were all bleeding (including minor, major, and life-threatening or disabling bleeding) and non-procedure-related bleeding over a period of 12 months. Most bleeding at the TAVI 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 (secondary composite 1) and a composite of death from cardiovascular causes, ischemic stroke, or myocardial infarction (secondary composite 2) at 1 year, with both outcomes tested sequentially for noninferiority (noninferiority margin, 7.5 percentage points) and superiority. RESULTS A total of 331 patients were assigned to receive aspirin alone and 334 were assigned to receive aspirin plus clopidogrel. A bleeding event occurred in 50 patients (15.1%) receiving aspirin alone and in 89 (26.6%) receiving aspirin plus clopidogrel (risk ratio, 0.57; 95% confidence interval [CI], 0.42 to 0.77; P=0.001). Non-procedure-related bleeding occurred in 50 patients (15.1%) and 83 patients (24.9%), respectively (risk ratio, 0.61; 95% CI, 0.44 to 0.83; P=0.005). A secondary composite 1 event occurred in 76 patients (23.0%) receiving aspirin alone and in 104 (31.1%) receiving aspirin plus clopidogrel (difference, −8.2 percentage points; 95% CI for noninferiority, −14.9 to −1.5; P<0.001; risk ratio, 0.74; 95% CI for superiority, 0.57 to 0.95; P=0.04). A secondary composite 2 event occurred in 32 patients (9.7%) and 33 patients (9.9%), respectively (difference, −0.2 percentage points; 95% CI for noninferiority, −4.7 to 4.3; P=0.004; risk ratio, 0.98; 95% CI for superiority, 0.62 to 1.55; P=0.93). A total of 44 patients (13.3%) and 32 (9.6%), respectively, received oral anticoagulation during the trial. CONCLUSIONS Among patients undergoing TAVI who did not have an indication for oral anticoagulation, the incidence of bleeding and the composite of bleeding or thromboembolic events at 1 year were significantly less frequent with aspirin than with aspirin plus clopidogrel administered for 3 months.

AB - BACKGROUND The effect of single as compared with dual antiplatelet treatment on bleeding and thromboembolic events after transcatheter aortic-valve implantation (TAVI) in patients who do not have an indication for long-term anticoagulation has not been well studied. METHODS In a randomized, controlled trial, we assigned a subgroup of patients who were undergoing TAVI and did not have an indication for long-term anticoagulation, in a 1:1 ratio, to receive aspirin alone or aspirin plus clopidogrel for 3 months. The two primary outcomes were all bleeding (including minor, major, and life-threatening or disabling bleeding) and non-procedure-related bleeding over a period of 12 months. Most bleeding at the TAVI 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 (secondary composite 1) and a composite of death from cardiovascular causes, ischemic stroke, or myocardial infarction (secondary composite 2) at 1 year, with both outcomes tested sequentially for noninferiority (noninferiority margin, 7.5 percentage points) and superiority. RESULTS A total of 331 patients were assigned to receive aspirin alone and 334 were assigned to receive aspirin plus clopidogrel. A bleeding event occurred in 50 patients (15.1%) receiving aspirin alone and in 89 (26.6%) receiving aspirin plus clopidogrel (risk ratio, 0.57; 95% confidence interval [CI], 0.42 to 0.77; P=0.001). Non-procedure-related bleeding occurred in 50 patients (15.1%) and 83 patients (24.9%), respectively (risk ratio, 0.61; 95% CI, 0.44 to 0.83; P=0.005). A secondary composite 1 event occurred in 76 patients (23.0%) receiving aspirin alone and in 104 (31.1%) receiving aspirin plus clopidogrel (difference, −8.2 percentage points; 95% CI for noninferiority, −14.9 to −1.5; P<0.001; risk ratio, 0.74; 95% CI for superiority, 0.57 to 0.95; P=0.04). A secondary composite 2 event occurred in 32 patients (9.7%) and 33 patients (9.9%), respectively (difference, −0.2 percentage points; 95% CI for noninferiority, −4.7 to 4.3; P=0.004; risk ratio, 0.98; 95% CI for superiority, 0.62 to 1.55; P=0.93). A total of 44 patients (13.3%) and 32 (9.6%), respectively, received oral anticoagulation during the trial. CONCLUSIONS Among patients undergoing TAVI who did not have an indication for oral anticoagulation, the incidence of bleeding and the composite of bleeding or thromboembolic events at 1 year were significantly less frequent with aspirin than with aspirin plus clopidogrel administered for 3 months.

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DO - 10.1056/NEJMoa2017815

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AN - SCOPUS:85090759061

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JO - New England Journal of Medicine

JF - New England Journal of Medicine

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ER -

Aspirin with or without clopidogrel after transcatheter aortic-valve implantation

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