Relation between Platelet Count and Platelet Reactivity to Thrombotic and Bleeding Risk: From the Assessment of Dual Antiplatelet Therapy with Drug-Eluting Stents Study

Gennaro Giustino; Ajay J. Kirtane; Philippe Généreux; Usman Baber; Bernhard Witzenbichler; Franz Josef Neumann; Giora Weisz; Akiko Maehara; Michael J. Rinaldi; Christopher Metzger; Timothy D. Henry; David A. Cox; Peter L. Duffy; Ernest L. Mazzaferri; Bruce R. Brodie; Thomas D. Stuckey; George D. Dangas; Dominic P. Francese; Claire Litherland; Roxana Mehran; Gregg W. Stone

doi:10.1016/j.amjcard.2016.03.001

Relation between Platelet Count and Platelet Reactivity to Thrombotic and Bleeding Risk: From the Assessment of Dual Antiplatelet Therapy with Drug-Eluting Stents Study

Gennaro Giustino, Ajay J. Kirtane, Philippe Généreux, Usman Baber, Bernhard Witzenbichler, Franz Josef Neumann, Giora Weisz, Akiko Maehara, Michael J. Rinaldi, Christopher Metzger, Timothy D. Henry, David A. Cox, Peter L. Duffy, Ernest L. Mazzaferri, Bruce R. Brodie, Thomas D. Stuckey, George D. Dangas, Dominic P. Francese, Claire Litherland, Roxana MehranGregg W. Stone

Medicine - Cardiology Division

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

17 Scopus citations

Abstract

Whether the association between platelet count (PC) and thrombotic and bleeding risk is independent of or varies by residual platelet reactivity to antiplatelet therapies is unclear. We sought to investigate the independent and combined effects of PC and platelet reactivity on thrombotic and bleeding risk after coronary artery implantation of drug-eluting stents (DES). Patients enrolled in the prospective, multicenter Assessment of Dual AntiPlatelet Therapy with Drug-Eluting Stents study were stratified by PC tertiles. The study cohort comprised 8,402 patients. By linear regression analysis, lower PC was strongly and independently associated with higher platelet reactive units (PRUs) on clopidogrel. After multivariable adjustment (including PRU and aspirin reactive units), high, but not low, PC tertile was independently associated with higher risk of thrombotic complications, including spontaneous myocardial infarction and stent thrombosis. Although no independent association was observed between PC tertiles and hemorrhagic risk, both high and low PC tertiles were associated with increased risk for all-cause mortality. After stratification of PC tertiles by tertiles of PRUs, the crude risk of thrombotic complications was highest in patients in the high PC and high PRU tertiles. By multivariable adjustment, PRU increases were uniformly associated with higher risk of thrombotic events across PC tertiles, without evidence of interaction. In conclusion, higher PCs and higher PRUs act independently and synergistically in determining thrombotic risk. Alongside PRU, PCs could be a simple hematological parameter to consider for risk stratification and in tailoring duration and potency of pharmacologic platelet inhibition after DES implantation.

Original language	English (US)
Pages (from-to)	1703-1713
Number of pages	11
Journal	American Journal of Cardiology
Volume	117
Issue number	11
DOIs	https://doi.org/10.1016/j.amjcard.2016.03.001
State	Published - Jun 1 2016

Bibliographical note

Funding Information:
Dr. Généreux receives Speaker's fee from Abbott Vascular and Edwards Lifescience; consulting fees from Cardiovascular Systems Inc.; and institutional research grant from Boston Scientific. Drs. Mehran and Dangas receives research grant support from Eli Lilly, AstraZeneca, The Medicines Company, BMS/Sanofi-Aventis; consulting fees from AstraZeneca, Bayer, CSL Behring, Janssen Pharmaceuticals, Merck, Osprey Medical Inc., Watermark Research Partners; and scientific advisory board from Abbott Laboratories, Boston Scientific, Covidien, Janssen Pharmaceuticals, The Medicines Company, Sanofi-Aventis. Dr. Kirtane: institutional research grants to Columbia University from Boston Scientific, Medtronic, Abbott Vascular, Abiomed, St. Jude Medical, Vascular Dynamics, and Eli Lilly. Dr. Witzenbichler receives consultant fees from Volcano and lecture fees from Elixir Medical Corp, Atrium Medical. Dr. Weisz: Advisory board Angioslide, AstraZeneca, Calore Medical, Corindus, Medivizor, Medtronic. Dr. Maehara receives grant support from Boston Scientific; is a consultant for Boston Scientific, ACIST; and receives speaker fee from St. Jude Medical. Dr. Rinaldi is a consultant for Abbott, Boston Scientific, St. Jude Medical, Volcano. Dr. Metzger receives symposium honoraria from Abbott Vascular, Boston Scientific, Bard; hand on proctor fees from Abbott Vascular, TriVascular. Dr. Henry: Scientific advisory board Abbott Vascular, Boston Scientific, and The Medicines Company; steering committee–TRANSLATE sponsored by Eli Lilly and 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. Stuckey is a member of Advisory board, Boston Scientific and receives speaker honoraria from Boston Scientific, Eli Lilly/Daiichi-Sankyo. The others have no conflicts of interest to disclose.

Funding Information:
The ADAPT-DES study ( NCT00638794 ) was sponsored by the Cardiovascular Research Foundation (New York, New York) and funded by research grants from Boston Scientific, Abbott Vascular, Medtronic, Cordis, Biosensors, The Medicines Company, Daiichi-Sankyo, Eli Lilly, Volcano, and Accumetrics.

Publisher Copyright:
© 2016 Elsevier Inc.

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Giustino, G., Kirtane, A. J., Généreux, P., Baber, U., Witzenbichler, B., Neumann, F. J., Weisz, G., Maehara, A., Rinaldi, M. J., Metzger, C., Henry, T. D., Cox, D. A., Duffy, P. L., Mazzaferri, E. L., Brodie, B. R., Stuckey, T. D., Dangas, G. D., Francese, D. P., Litherland, C., ... Stone, G. W. (2016). Relation between Platelet Count and Platelet Reactivity to Thrombotic and Bleeding Risk: From the Assessment of Dual Antiplatelet Therapy with Drug-Eluting Stents Study. American Journal of Cardiology, 117(11), 1703-1713. https://doi.org/10.1016/j.amjcard.2016.03.001

Relation between Platelet Count and Platelet Reactivity to Thrombotic and Bleeding Risk: From the Assessment of Dual Antiplatelet Therapy with Drug-Eluting Stents Study. / Giustino, Gennaro; Kirtane, Ajay J.; Généreux, Philippe et al.
In: American Journal of Cardiology, Vol. 117, No. 11, 01.06.2016, p. 1703-1713.

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

Giustino, G, Kirtane, AJ, Généreux, P, Baber, U, Witzenbichler, B, Neumann, FJ, Weisz, G, Maehara, A, Rinaldi, MJ, Metzger, C, Henry, TD, Cox, DA, Duffy, PL, Mazzaferri, EL, Brodie, BR, Stuckey, TD, Dangas, GD, Francese, DP, Litherland, C, Mehran, R & Stone, GW 2016, 'Relation between Platelet Count and Platelet Reactivity to Thrombotic and Bleeding Risk: From the Assessment of Dual Antiplatelet Therapy with Drug-Eluting Stents Study', American Journal of Cardiology, vol. 117, no. 11, pp. 1703-1713. https://doi.org/10.1016/j.amjcard.2016.03.001

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title = "Relation between Platelet Count and Platelet Reactivity to Thrombotic and Bleeding Risk: From the Assessment of Dual Antiplatelet Therapy with Drug-Eluting Stents Study",

abstract = "Whether the association between platelet count (PC) and thrombotic and bleeding risk is independent of or varies by residual platelet reactivity to antiplatelet therapies is unclear. We sought to investigate the independent and combined effects of PC and platelet reactivity on thrombotic and bleeding risk after coronary artery implantation of drug-eluting stents (DES). Patients enrolled in the prospective, multicenter Assessment of Dual AntiPlatelet Therapy with Drug-Eluting Stents study were stratified by PC tertiles. The study cohort comprised 8,402 patients. By linear regression analysis, lower PC was strongly and independently associated with higher platelet reactive units (PRUs) on clopidogrel. After multivariable adjustment (including PRU and aspirin reactive units), high, but not low, PC tertile was independently associated with higher risk of thrombotic complications, including spontaneous myocardial infarction and stent thrombosis. Although no independent association was observed between PC tertiles and hemorrhagic risk, both high and low PC tertiles were associated with increased risk for all-cause mortality. After stratification of PC tertiles by tertiles of PRUs, the crude risk of thrombotic complications was highest in patients in the high PC and high PRU tertiles. By multivariable adjustment, PRU increases were uniformly associated with higher risk of thrombotic events across PC tertiles, without evidence of interaction. In conclusion, higher PCs and higher PRUs act independently and synergistically in determining thrombotic risk. Alongside PRU, PCs could be a simple hematological parameter to consider for risk stratification and in tailoring duration and potency of pharmacologic platelet inhibition after DES implantation.",

author = "Gennaro Giustino and Kirtane, {Ajay J.} and Philippe G{\'e}n{\'e}reux and Usman Baber and Bernhard Witzenbichler and Neumann, {Franz Josef} and Giora Weisz and Akiko Maehara and Rinaldi, {Michael J.} and Christopher Metzger and Henry, {Timothy D.} and Cox, {David A.} and Duffy, {Peter L.} and Mazzaferri, {Ernest L.} and Brodie, {Bruce R.} and Stuckey, {Thomas D.} and Dangas, {George D.} and Francese, {Dominic P.} and Claire Litherland and Roxana Mehran and Stone, {Gregg W.}",

note = "Funding Information: Dr. G{\'e}n{\'e}reux receives Speaker's fee from Abbott Vascular and Edwards Lifescience; consulting fees from Cardiovascular Systems Inc.; and institutional research grant from Boston Scientific. Drs. Mehran and Dangas receives research grant support from Eli Lilly, AstraZeneca, The Medicines Company, BMS/Sanofi-Aventis; consulting fees from AstraZeneca, Bayer, CSL Behring, Janssen Pharmaceuticals, Merck, Osprey Medical Inc., Watermark Research Partners; and scientific advisory board from Abbott Laboratories, Boston Scientific, Covidien, Janssen Pharmaceuticals, The Medicines Company, Sanofi-Aventis. Dr. Kirtane: institutional research grants to Columbia University from Boston Scientific, Medtronic, Abbott Vascular, Abiomed, St. Jude Medical, Vascular Dynamics, and Eli Lilly. Dr. Witzenbichler receives consultant fees from Volcano and lecture fees from Elixir Medical Corp, Atrium Medical. Dr. Weisz: Advisory board Angioslide, AstraZeneca, Calore Medical, Corindus, Medivizor, Medtronic. Dr. Maehara receives grant support from Boston Scientific; is a consultant for Boston Scientific, ACIST; and receives speaker fee from St. Jude Medical. Dr. Rinaldi is a consultant for Abbott, Boston Scientific, St. Jude Medical, Volcano. Dr. Metzger receives symposium honoraria from Abbott Vascular, Boston Scientific, Bard; hand on proctor fees from Abbott Vascular, TriVascular. Dr. Henry: Scientific advisory board Abbott Vascular, Boston Scientific, and The Medicines Company; steering committee–TRANSLATE sponsored by Eli Lilly and 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. Stuckey is a member of Advisory board, Boston Scientific and receives speaker honoraria from Boston Scientific, Eli Lilly/Daiichi-Sankyo. The others have no conflicts of interest to disclose. Funding Information: The ADAPT-DES study ( NCT00638794 ) was sponsored by the Cardiovascular Research Foundation (New York, New York) and funded by research grants from Boston Scientific, Abbott Vascular, Medtronic, Cordis, Biosensors, The Medicines Company, Daiichi-Sankyo, Eli Lilly, Volcano, and Accumetrics. Publisher Copyright: {\textcopyright} 2016 Elsevier Inc.",

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language = "English (US)",

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T1 - Relation between Platelet Count and Platelet Reactivity to Thrombotic and Bleeding Risk

T2 - From the Assessment of Dual Antiplatelet Therapy with Drug-Eluting Stents Study

AU - Giustino, Gennaro

AU - Kirtane, Ajay J.

AU - Généreux, Philippe

AU - Baber, Usman

AU - Witzenbichler, Bernhard

AU - Neumann, Franz Josef

AU - Weisz, Giora

AU - Maehara, Akiko

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AU - Mazzaferri, Ernest L.

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AU - Litherland, Claire

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AU - Stone, Gregg W.

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N2 - Whether the association between platelet count (PC) and thrombotic and bleeding risk is independent of or varies by residual platelet reactivity to antiplatelet therapies is unclear. We sought to investigate the independent and combined effects of PC and platelet reactivity on thrombotic and bleeding risk after coronary artery implantation of drug-eluting stents (DES). Patients enrolled in the prospective, multicenter Assessment of Dual AntiPlatelet Therapy with Drug-Eluting Stents study were stratified by PC tertiles. The study cohort comprised 8,402 patients. By linear regression analysis, lower PC was strongly and independently associated with higher platelet reactive units (PRUs) on clopidogrel. After multivariable adjustment (including PRU and aspirin reactive units), high, but not low, PC tertile was independently associated with higher risk of thrombotic complications, including spontaneous myocardial infarction and stent thrombosis. Although no independent association was observed between PC tertiles and hemorrhagic risk, both high and low PC tertiles were associated with increased risk for all-cause mortality. After stratification of PC tertiles by tertiles of PRUs, the crude risk of thrombotic complications was highest in patients in the high PC and high PRU tertiles. By multivariable adjustment, PRU increases were uniformly associated with higher risk of thrombotic events across PC tertiles, without evidence of interaction. In conclusion, higher PCs and higher PRUs act independently and synergistically in determining thrombotic risk. Alongside PRU, PCs could be a simple hematological parameter to consider for risk stratification and in tailoring duration and potency of pharmacologic platelet inhibition after DES implantation.

AB - Whether the association between platelet count (PC) and thrombotic and bleeding risk is independent of or varies by residual platelet reactivity to antiplatelet therapies is unclear. We sought to investigate the independent and combined effects of PC and platelet reactivity on thrombotic and bleeding risk after coronary artery implantation of drug-eluting stents (DES). Patients enrolled in the prospective, multicenter Assessment of Dual AntiPlatelet Therapy with Drug-Eluting Stents study were stratified by PC tertiles. The study cohort comprised 8,402 patients. By linear regression analysis, lower PC was strongly and independently associated with higher platelet reactive units (PRUs) on clopidogrel. After multivariable adjustment (including PRU and aspirin reactive units), high, but not low, PC tertile was independently associated with higher risk of thrombotic complications, including spontaneous myocardial infarction and stent thrombosis. Although no independent association was observed between PC tertiles and hemorrhagic risk, both high and low PC tertiles were associated with increased risk for all-cause mortality. After stratification of PC tertiles by tertiles of PRUs, the crude risk of thrombotic complications was highest in patients in the high PC and high PRU tertiles. By multivariable adjustment, PRU increases were uniformly associated with higher risk of thrombotic events across PC tertiles, without evidence of interaction. In conclusion, higher PCs and higher PRUs act independently and synergistically in determining thrombotic risk. Alongside PRU, PCs could be a simple hematological parameter to consider for risk stratification and in tailoring duration and potency of pharmacologic platelet inhibition after DES implantation.

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Relation between Platelet Count and Platelet Reactivity to Thrombotic and Bleeding Risk: From the Assessment of Dual Antiplatelet Therapy with Drug-Eluting Stents Study

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