Impact of hemoglobin a1c levels on residual platelet reactivity and outcomes after insertion of coronary drug-eluting stents (from the ADAPT-DES Study)

Mikkel M. Schoos; George D. Dangas; Roxana Mehran; Ajay J. Kirtane; Jennifer Yu; Claire Litherland; Peter Clemmensen; Thomas D. Stuckey; Bernhard Witzenbichler; Giora Weisz; Michael J. Rinaldi; Franz Josef Neumann; D. Christopher Metzger; Timothy D. Henry; David A. Cox; Peter L. Duffy; Bruce R. Brodie; Ernest L. Mazzaferri; Akiko Maehara; Gregg W. Stone

doi:10.1016/j.amjcard.2015.10.037

Impact of hemoglobin a1c levels on residual platelet reactivity and outcomes after insertion of coronary drug-eluting stents (from the ADAPT-DES Study)

Mikkel M. Schoos, George D. Dangas, Roxana Mehran, Ajay J. Kirtane, Jennifer Yu, Claire Litherland, Peter Clemmensen, Thomas D. Stuckey, Bernhard Witzenbichler, Giora Weisz, Michael J. Rinaldi, Franz Josef Neumann, D. Christopher Metzger, Timothy D. Henry, David A. Cox, Peter L. Duffy, Bruce R. Brodie, Ernest L. Mazzaferri, Akiko Maehara, Gregg W. Stone

Medicine - Cardiology Division

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15 Scopus citations

Abstract

An increasing hemoglobin A1c (HbA1c) level portends an adverse cardiovascular prognosis; however, the association between glycemic control, platelet reactivity, and outcomes after percutaneous coronary intervention (PCI) with drug-eluting stents (DES) is unknown. We sought to investigate whether HbA1c levels are associated with high platelet reactivity (HPR) in patients loaded with clopidogrel and aspirin, thereby constituting an argument for intensified antiplatelet therapy in patients with poor glycemic control. In the prospective, multicenter Assessment of Dual Antiplatelet Therapy With Drug Eluting Stents registry, HbA1c levels were measured as clinically indicated in 1,145 of 8,582 patients, stratified by HbA1c <6.5% (n = 551, 48.12%), 6.5% to 8.5% (n = 423, 36.9%), and >8.5% (n = 171, 14.9%). HPR on clopidogrel and aspirin was defined after PCI as P2Y12 reaction units (PRU) >208 and aspirin reaction units >550, respectively. HPR on clopidogrel was frequent (48.3%), whereas HPR on aspirin was not (3.9%). Patients with HbA1c >8.5% were younger, more likely non-Caucasian, had a greater body mass index, and more insulin-treated diabetes and acute coronary syndromes. Proportions of PRU >208 (42.5%, 50.2%, and 62.3%, p <0.001) and rates of definite or probable stent thrombosis (ST; 0.9%, 2.7%, and 4.2%, p = 0.02) increased progressively with HbA1c groups. Clinically relevant bleeding was greatest in the intermediate HbA1c group (8.2% vs 13.1% vs 9.5%, p = 0.04). In adjusted models that included PRU, high HbA1c levels (>8.5) remained associated with ST (hazard ratio 3.92, 95% CI 1.29 to 12.66, p = 0.02) and cardiac death (hazard ratio 4.24, 95% CI 1.41 to 12.70) but not bleeding at 2-year follow-up. There was no association between aspirin reaction units >550 and HbA1c levels. In conclusion, in this large-scale study, HbA1c and HPR were positively associated, but the clinical effect on adverse outcome was driven by poor glycemic control, which predicted ST and cardiac death after PCI regardless of PRU levels, warranting efforts to improve glycemic control after DES implantation in patients with diabetes mellitus.

Original language	English (US)
Pages (from-to)	192-200
Number of pages	9
Journal	American Journal of Cardiology
Volume	117
Issue number	2
DOIs	https://doi.org/10.1016/j.amjcard.2015.10.037
State	Published - 2016

Bibliographical note

Funding Information:
Drs. Dangas and Mehran receives institutional research grant support from The Medicines Company, Bristol-Myers Squibb/Sanofi and Eli Lilly, and Company/Daiichi Sankyo and are a consultant to Abbott Vascular, AstraZeneca, Boston Scientific, Covidien, Janssen Pharmaceuticals, Regado Biosciences, Maya Medical, Merck & Co., and The Medicines Company. Dr. Kirtane receives institutional research grants to Columbia University from Boston Scientific, Medtronic, Abbott Vascular, Abiomed, St. Jude Medical, Vascular Dynamics, and Eli Lilly. Dr. Clemmensen has been involved in research contracts with Abbott, AstraZeneca, Aventis, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Eli Lilly, Pfizer, The Medicines Company, Nycomed, Janssen, Medtronic, Organon, Merck, Myogen, Pharmacia, Regado, Sanofi, Searle, Servier and consulting with Evolva, Fibrex, AstraZeneca, Bayer, Boehringer Ingelheim, Mitsubishi Pharma and received speakers fee from Aventis, Bayer, Bristol-Myers Squibb, Daiichi Sankyo, Eli Lilly, Merck, Medtronic, Philips, The Medicines Company, Nycomed, Pfizer, Sanofi, and Servier. Dr. Stuckey: Advisory board–Boston Scientific; speaker honoraria–Boston Scientific, Eli Lilly/Daiichi Sankyo. Dr. Witzenbichler is a consultant for Volcano and receives lecture fees from Elixir Medical Corp, Atrium Medical. Dr. Weisz: Advisory board–Angioslide, AstraZeneca, Calore Medical, Corindus, Medivizor, Medtronic. Dr. Rinaldi is a consultant for Abbott, Boston Scientific, St. Jude Medical. Dr. Metzger: Symposium honoraria–Abbott Vascular, Boston Scientific, Bard and receives hand on proctor fees from Abbott Vascular, TriVascular. Dr. Henry: Scientific advisory goard–Abbott Vascular, Boston Scientific, and The Medicines Company; steering committee–TRANSLATE sponsored by Eli Lilly and Company/Daiichi Sankyo. Dr. Cox is a consultant for Abbott Vascular, Boston Scientific Corporation, Medtronic, The Medicines Company. Dr. Duffy is a consultant/speaker for Philips Medical/Volcano Corporation. Dr. Maehara receives grant support from Boston Scientific, is a consultant for Boston Scientific, ACIST and receives speaker fee from St. Jude Medical.

Publisher Copyright:
© 2016 Elsevier Inc.

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Schoos, M. M., Dangas, G. D., Mehran, R., Kirtane, A. J., Yu, J., Litherland, C., Clemmensen, P., Stuckey, T. D., Witzenbichler, B., Weisz, G., Rinaldi, M. J., Neumann, F. J., Metzger, D. C., Henry, T. D., Cox, D. A., Duffy, P. L., Brodie, B. R., Mazzaferri, E. L., Maehara, A., & Stone, G. W. (2016). Impact of hemoglobin a1c levels on residual platelet reactivity and outcomes after insertion of coronary drug-eluting stents (from the ADAPT-DES Study). American Journal of Cardiology, 117(2), 192-200. https://doi.org/10.1016/j.amjcard.2015.10.037

Schoos, MM, Dangas, GD, Mehran, R, Kirtane, AJ, Yu, J, Litherland, C, Clemmensen, P, Stuckey, TD, Witzenbichler, B, Weisz, G, Rinaldi, MJ, Neumann, FJ, Metzger, DC, Henry, TD, Cox, DA, Duffy, PL, Brodie, BR, Mazzaferri, EL, Maehara, A & Stone, GW 2016, 'Impact of hemoglobin a1c levels on residual platelet reactivity and outcomes after insertion of coronary drug-eluting stents (from the ADAPT-DES Study)', American Journal of Cardiology, vol. 117, no. 2, pp. 192-200. https://doi.org/10.1016/j.amjcard.2015.10.037

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title = "Impact of hemoglobin a1c levels on residual platelet reactivity and outcomes after insertion of coronary drug-eluting stents (from the ADAPT-DES Study)",

abstract = "An increasing hemoglobin A1c (HbA1c) level portends an adverse cardiovascular prognosis; however, the association between glycemic control, platelet reactivity, and outcomes after percutaneous coronary intervention (PCI) with drug-eluting stents (DES) is unknown. We sought to investigate whether HbA1c levels are associated with high platelet reactivity (HPR) in patients loaded with clopidogrel and aspirin, thereby constituting an argument for intensified antiplatelet therapy in patients with poor glycemic control. In the prospective, multicenter Assessment of Dual Antiplatelet Therapy With Drug Eluting Stents registry, HbA1c levels were measured as clinically indicated in 1,145 of 8,582 patients, stratified by HbA1c <6.5% (n = 551, 48.12%), 6.5% to 8.5% (n = 423, 36.9%), and >8.5% (n = 171, 14.9%). HPR on clopidogrel and aspirin was defined after PCI as P2Y12 reaction units (PRU) >208 and aspirin reaction units >550, respectively. HPR on clopidogrel was frequent (48.3%), whereas HPR on aspirin was not (3.9%). Patients with HbA1c >8.5% were younger, more likely non-Caucasian, had a greater body mass index, and more insulin-treated diabetes and acute coronary syndromes. Proportions of PRU >208 (42.5%, 50.2%, and 62.3%, p <0.001) and rates of definite or probable stent thrombosis (ST; 0.9%, 2.7%, and 4.2%, p = 0.02) increased progressively with HbA1c groups. Clinically relevant bleeding was greatest in the intermediate HbA1c group (8.2% vs 13.1% vs 9.5%, p = 0.04). In adjusted models that included PRU, high HbA1c levels (>8.5) remained associated with ST (hazard ratio 3.92, 95% CI 1.29 to 12.66, p = 0.02) and cardiac death (hazard ratio 4.24, 95% CI 1.41 to 12.70) but not bleeding at 2-year follow-up. There was no association between aspirin reaction units >550 and HbA1c levels. In conclusion, in this large-scale study, HbA1c and HPR were positively associated, but the clinical effect on adverse outcome was driven by poor glycemic control, which predicted ST and cardiac death after PCI regardless of PRU levels, warranting efforts to improve glycemic control after DES implantation in patients with diabetes mellitus.",

author = "Schoos, {Mikkel M.} and Dangas, {George D.} and Roxana Mehran and Kirtane, {Ajay J.} and Jennifer Yu and Claire Litherland and Peter Clemmensen and Stuckey, {Thomas D.} and Bernhard Witzenbichler and Giora Weisz and Rinaldi, {Michael J.} and Neumann, {Franz Josef} and Metzger, {D. Christopher} and Henry, {Timothy D.} and Cox, {David A.} and Duffy, {Peter L.} and Brodie, {Bruce R.} and Mazzaferri, {Ernest L.} and Akiko Maehara and Stone, {Gregg W.}",

note = "Funding Information: Drs. Dangas and Mehran receives institutional research grant support from The Medicines Company, Bristol-Myers Squibb/Sanofi and Eli Lilly, and Company/Daiichi Sankyo and are a consultant to Abbott Vascular, AstraZeneca, Boston Scientific, Covidien, Janssen Pharmaceuticals, Regado Biosciences, Maya Medical, Merck & Co., and The Medicines Company. Dr. Kirtane receives institutional research grants to Columbia University from Boston Scientific, Medtronic, Abbott Vascular, Abiomed, St. Jude Medical, Vascular Dynamics, and Eli Lilly. Dr. Clemmensen has been involved in research contracts with Abbott, AstraZeneca, Aventis, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Eli Lilly, Pfizer, The Medicines Company, Nycomed, Janssen, Medtronic, Organon, Merck, Myogen, Pharmacia, Regado, Sanofi, Searle, Servier and consulting with Evolva, Fibrex, AstraZeneca, Bayer, Boehringer Ingelheim, Mitsubishi Pharma and received speakers fee from Aventis, Bayer, Bristol-Myers Squibb, Daiichi Sankyo, Eli Lilly, Merck, Medtronic, Philips, The Medicines Company, Nycomed, Pfizer, Sanofi, and Servier. Dr. Stuckey: Advisory board–Boston Scientific; speaker honoraria–Boston Scientific, Eli Lilly/Daiichi Sankyo. Dr. Witzenbichler is a consultant for Volcano and receives lecture fees from Elixir Medical Corp, Atrium Medical. Dr. Weisz: Advisory board–Angioslide, AstraZeneca, Calore Medical, Corindus, Medivizor, Medtronic. Dr. Rinaldi is a consultant for Abbott, Boston Scientific, St. Jude Medical. Dr. Metzger: Symposium honoraria–Abbott Vascular, Boston Scientific, Bard and receives hand on proctor fees from Abbott Vascular, TriVascular. Dr. Henry: Scientific advisory goard–Abbott Vascular, Boston Scientific, and The Medicines Company; steering committee–TRANSLATE sponsored by Eli Lilly and Company/Daiichi Sankyo. Dr. Cox is a consultant for Abbott Vascular, Boston Scientific Corporation, Medtronic, The Medicines Company. Dr. Duffy is a consultant/speaker for Philips Medical/Volcano Corporation. Dr. Maehara receives grant support from Boston Scientific, is a consultant for Boston Scientific, ACIST and receives speaker fee from St. Jude Medical. Publisher Copyright: {\textcopyright} 2016 Elsevier Inc.",

year = "2016",

doi = "10.1016/j.amjcard.2015.10.037",

language = "English (US)",

volume = "117",

pages = "192--200",

journal = "American Journal of Cardiology",

issn = "0002-9149",

publisher = "Elsevier Inc.",

number = "2",

}

TY - JOUR

T1 - Impact of hemoglobin a1c levels on residual platelet reactivity and outcomes after insertion of coronary drug-eluting stents (from the ADAPT-DES Study)

AU - Schoos, Mikkel M.

AU - Dangas, George D.

AU - Mehran, Roxana

AU - Kirtane, Ajay J.

AU - Yu, Jennifer

AU - Litherland, Claire

AU - Clemmensen, Peter

AU - Stuckey, Thomas D.

AU - Witzenbichler, Bernhard

AU - Weisz, Giora

AU - Rinaldi, Michael J.

AU - Neumann, Franz Josef

AU - Metzger, D. Christopher

AU - Henry, Timothy D.

AU - Cox, David A.

AU - Duffy, Peter L.

AU - Brodie, Bruce R.

AU - Mazzaferri, Ernest L.

AU - Maehara, Akiko

AU - Stone, Gregg W.

N1 - Funding Information: Drs. Dangas and Mehran receives institutional research grant support from The Medicines Company, Bristol-Myers Squibb/Sanofi and Eli Lilly, and Company/Daiichi Sankyo and are a consultant to Abbott Vascular, AstraZeneca, Boston Scientific, Covidien, Janssen Pharmaceuticals, Regado Biosciences, Maya Medical, Merck & Co., and The Medicines Company. Dr. Kirtane receives institutional research grants to Columbia University from Boston Scientific, Medtronic, Abbott Vascular, Abiomed, St. Jude Medical, Vascular Dynamics, and Eli Lilly. Dr. Clemmensen has been involved in research contracts with Abbott, AstraZeneca, Aventis, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Eli Lilly, Pfizer, The Medicines Company, Nycomed, Janssen, Medtronic, Organon, Merck, Myogen, Pharmacia, Regado, Sanofi, Searle, Servier and consulting with Evolva, Fibrex, AstraZeneca, Bayer, Boehringer Ingelheim, Mitsubishi Pharma and received speakers fee from Aventis, Bayer, Bristol-Myers Squibb, Daiichi Sankyo, Eli Lilly, Merck, Medtronic, Philips, The Medicines Company, Nycomed, Pfizer, Sanofi, and Servier. Dr. Stuckey: Advisory board–Boston Scientific; speaker honoraria–Boston Scientific, Eli Lilly/Daiichi Sankyo. Dr. Witzenbichler is a consultant for Volcano and receives lecture fees from Elixir Medical Corp, Atrium Medical. Dr. Weisz: Advisory board–Angioslide, AstraZeneca, Calore Medical, Corindus, Medivizor, Medtronic. Dr. Rinaldi is a consultant for Abbott, Boston Scientific, St. Jude Medical. Dr. Metzger: Symposium honoraria–Abbott Vascular, Boston Scientific, Bard and receives hand on proctor fees from Abbott Vascular, TriVascular. Dr. Henry: Scientific advisory goard–Abbott Vascular, Boston Scientific, and The Medicines Company; steering committee–TRANSLATE sponsored by Eli Lilly and Company/Daiichi Sankyo. Dr. Cox is a consultant for Abbott Vascular, Boston Scientific Corporation, Medtronic, The Medicines Company. Dr. Duffy is a consultant/speaker for Philips Medical/Volcano Corporation. Dr. Maehara receives grant support from Boston Scientific, is a consultant for Boston Scientific, ACIST and receives speaker fee from St. Jude Medical. Publisher Copyright: © 2016 Elsevier Inc.

PY - 2016

Y1 - 2016

N2 - An increasing hemoglobin A1c (HbA1c) level portends an adverse cardiovascular prognosis; however, the association between glycemic control, platelet reactivity, and outcomes after percutaneous coronary intervention (PCI) with drug-eluting stents (DES) is unknown. We sought to investigate whether HbA1c levels are associated with high platelet reactivity (HPR) in patients loaded with clopidogrel and aspirin, thereby constituting an argument for intensified antiplatelet therapy in patients with poor glycemic control. In the prospective, multicenter Assessment of Dual Antiplatelet Therapy With Drug Eluting Stents registry, HbA1c levels were measured as clinically indicated in 1,145 of 8,582 patients, stratified by HbA1c <6.5% (n = 551, 48.12%), 6.5% to 8.5% (n = 423, 36.9%), and >8.5% (n = 171, 14.9%). HPR on clopidogrel and aspirin was defined after PCI as P2Y12 reaction units (PRU) >208 and aspirin reaction units >550, respectively. HPR on clopidogrel was frequent (48.3%), whereas HPR on aspirin was not (3.9%). Patients with HbA1c >8.5% were younger, more likely non-Caucasian, had a greater body mass index, and more insulin-treated diabetes and acute coronary syndromes. Proportions of PRU >208 (42.5%, 50.2%, and 62.3%, p <0.001) and rates of definite or probable stent thrombosis (ST; 0.9%, 2.7%, and 4.2%, p = 0.02) increased progressively with HbA1c groups. Clinically relevant bleeding was greatest in the intermediate HbA1c group (8.2% vs 13.1% vs 9.5%, p = 0.04). In adjusted models that included PRU, high HbA1c levels (>8.5) remained associated with ST (hazard ratio 3.92, 95% CI 1.29 to 12.66, p = 0.02) and cardiac death (hazard ratio 4.24, 95% CI 1.41 to 12.70) but not bleeding at 2-year follow-up. There was no association between aspirin reaction units >550 and HbA1c levels. In conclusion, in this large-scale study, HbA1c and HPR were positively associated, but the clinical effect on adverse outcome was driven by poor glycemic control, which predicted ST and cardiac death after PCI regardless of PRU levels, warranting efforts to improve glycemic control after DES implantation in patients with diabetes mellitus.

AB - An increasing hemoglobin A1c (HbA1c) level portends an adverse cardiovascular prognosis; however, the association between glycemic control, platelet reactivity, and outcomes after percutaneous coronary intervention (PCI) with drug-eluting stents (DES) is unknown. We sought to investigate whether HbA1c levels are associated with high platelet reactivity (HPR) in patients loaded with clopidogrel and aspirin, thereby constituting an argument for intensified antiplatelet therapy in patients with poor glycemic control. In the prospective, multicenter Assessment of Dual Antiplatelet Therapy With Drug Eluting Stents registry, HbA1c levels were measured as clinically indicated in 1,145 of 8,582 patients, stratified by HbA1c <6.5% (n = 551, 48.12%), 6.5% to 8.5% (n = 423, 36.9%), and >8.5% (n = 171, 14.9%). HPR on clopidogrel and aspirin was defined after PCI as P2Y12 reaction units (PRU) >208 and aspirin reaction units >550, respectively. HPR on clopidogrel was frequent (48.3%), whereas HPR on aspirin was not (3.9%). Patients with HbA1c >8.5% were younger, more likely non-Caucasian, had a greater body mass index, and more insulin-treated diabetes and acute coronary syndromes. Proportions of PRU >208 (42.5%, 50.2%, and 62.3%, p <0.001) and rates of definite or probable stent thrombosis (ST; 0.9%, 2.7%, and 4.2%, p = 0.02) increased progressively with HbA1c groups. Clinically relevant bleeding was greatest in the intermediate HbA1c group (8.2% vs 13.1% vs 9.5%, p = 0.04). In adjusted models that included PRU, high HbA1c levels (>8.5) remained associated with ST (hazard ratio 3.92, 95% CI 1.29 to 12.66, p = 0.02) and cardiac death (hazard ratio 4.24, 95% CI 1.41 to 12.70) but not bleeding at 2-year follow-up. There was no association between aspirin reaction units >550 and HbA1c levels. In conclusion, in this large-scale study, HbA1c and HPR were positively associated, but the clinical effect on adverse outcome was driven by poor glycemic control, which predicted ST and cardiac death after PCI regardless of PRU levels, warranting efforts to improve glycemic control after DES implantation in patients with diabetes mellitus.

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Impact of hemoglobin a1c levels on residual platelet reactivity and outcomes after insertion of coronary drug-eluting stents (from the ADAPT-DES Study)

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