Quantifying Ischemic Risk After Percutaneous Coronary Intervention Attributable to High Platelet Reactivity on Clopidogrel (From the Assessment of Dual Antiplatelet Therapy with Drug-Eluting Stents Study)

Björn Redfors, Ori Ben-Yehuda, Sheng Hsuan Lin, Ariel Furer, Ajay J. Kirtane, Bernhard Witzenbichler, Giora Weisz, Thomas D. Stuckey, Akiko Maehara, Philippe Genereux, Gennaro Giustino, Michael J. Rinaldi, Franz Josef Neumann, D. Christopher Metzger, Timothy D. Henry, David A. Cox, Peter L. Duffy, Ernest L. Mazzaferri, Girma Minalu Ayele, Roxana MehranGary S. Mintz, Gregg W. Stone

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Patients at high risk of thrombotic events after percutaneous coronary intervention (PCI) may potentially benefit from intensified antiplatelet therapy. However, more potent antiplatelet therapy would be expected to only overcome risk that is mediated by high platelet reactivity (PR). We used mediation analysis to determine the contribution of residual PR to the 2-year risk of major adverse cardiac events (MACE; the composite of cardiac death, myocardial infarction, or stent thrombosis) associated with clinical risk factors after PCI with drug-eluting stents (DES) in 8,374 patients from the prospective, multicenter Assessment of Dual AntiPlatelet Therapy with Drug-Eluting Stents (ADAPT-DES) registry. Residual PR on clopidogrel, as measured by the VerifyNow P2Y12 point-of-care assay, was included as a continuous linear mediator variable in Cox proportional hazards regression. Among 7 factors independently associated with 2-year MACE, residual PR partly mediated the effect of diabetes (13.4% attributable risk), anemia (22.9% attributable risk), and acute coronary syndromes (7.3% attributable risk). A PR-mediated effect inversely affected the MACE risk associated with smoking (10.4% attributable risk). The increased ischemic risk of chronic kidney disease, multivessel disease, and previous myocardial infarction were not mediated by residual PR. In conclusion, high residual PR mediates little or none of the increased 2-year MACE risk associated with baseline risk factors in patients treated with clopidogrel after successful PCI with DES. Intensifying antiplatelet therapy is therefore unlikely to substantially mitigate the excess ischemic risk from these variables.

Original languageEnglish (US)
Pages (from-to)917-923
Number of pages7
JournalAmerican Journal of Cardiology
Volume120
Issue number6
DOIs
StatePublished - Sep 15 2017
Externally publishedYes

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clopidogrel
Drug-Eluting Stents
Percutaneous Coronary Intervention
Blood Platelets
Therapeutics
Point-of-Care Systems
Myocardial Infarction

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

Cite this

Redfors, Björn ; Ben-Yehuda, Ori ; Lin, Sheng Hsuan ; Furer, Ariel ; Kirtane, Ajay J. ; Witzenbichler, Bernhard ; Weisz, Giora ; Stuckey, Thomas D. ; Maehara, Akiko ; Genereux, Philippe ; Giustino, Gennaro ; Rinaldi, Michael J. ; Neumann, Franz Josef ; Metzger, D. Christopher ; Henry, Timothy D. ; Cox, David A. ; Duffy, Peter L. ; Mazzaferri, Ernest L. ; Ayele, Girma Minalu ; Mehran, Roxana ; Mintz, Gary S. ; Stone, Gregg W. / Quantifying Ischemic Risk After Percutaneous Coronary Intervention Attributable to High Platelet Reactivity on Clopidogrel (From the Assessment of Dual Antiplatelet Therapy with Drug-Eluting Stents Study). In: American Journal of Cardiology. 2017 ; Vol. 120, No. 6. pp. 917-923.
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abstract = "Patients at high risk of thrombotic events after percutaneous coronary intervention (PCI) may potentially benefit from intensified antiplatelet therapy. However, more potent antiplatelet therapy would be expected to only overcome risk that is mediated by high platelet reactivity (PR). We used mediation analysis to determine the contribution of residual PR to the 2-year risk of major adverse cardiac events (MACE; the composite of cardiac death, myocardial infarction, or stent thrombosis) associated with clinical risk factors after PCI with drug-eluting stents (DES) in 8,374 patients from the prospective, multicenter Assessment of Dual AntiPlatelet Therapy with Drug-Eluting Stents (ADAPT-DES) registry. Residual PR on clopidogrel, as measured by the VerifyNow P2Y12 point-of-care assay, was included as a continuous linear mediator variable in Cox proportional hazards regression. Among 7 factors independently associated with 2-year MACE, residual PR partly mediated the effect of diabetes (13.4{\%} attributable risk), anemia (22.9{\%} attributable risk), and acute coronary syndromes (7.3{\%} attributable risk). A PR-mediated effect inversely affected the MACE risk associated with smoking (10.4{\%} attributable risk). The increased ischemic risk of chronic kidney disease, multivessel disease, and previous myocardial infarction were not mediated by residual PR. In conclusion, high residual PR mediates little or none of the increased 2-year MACE risk associated with baseline risk factors in patients treated with clopidogrel after successful PCI with DES. Intensifying antiplatelet therapy is therefore unlikely to substantially mitigate the excess ischemic risk from these variables.",
author = "Bj{\"o}rn Redfors and Ori Ben-Yehuda and Lin, {Sheng Hsuan} and Ariel Furer and Kirtane, {Ajay J.} and Bernhard Witzenbichler and Giora Weisz and Stuckey, {Thomas D.} and Akiko Maehara and Philippe Genereux and Gennaro Giustino 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 Mazzaferri, {Ernest L.} and Ayele, {Girma Minalu} and Roxana Mehran and Mintz, {Gary S.} and Stone, {Gregg W.}",
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Redfors, B, Ben-Yehuda, O, Lin, SH, Furer, A, Kirtane, AJ, Witzenbichler, B, Weisz, G, Stuckey, TD, Maehara, A, Genereux, P, Giustino, G, Rinaldi, MJ, Neumann, FJ, Metzger, DC, Henry, TD, Cox, DA, Duffy, PL, Mazzaferri, EL, Ayele, GM, Mehran, R, Mintz, GS & Stone, GW 2017, 'Quantifying Ischemic Risk After Percutaneous Coronary Intervention Attributable to High Platelet Reactivity on Clopidogrel (From the Assessment of Dual Antiplatelet Therapy with Drug-Eluting Stents Study)', American Journal of Cardiology, vol. 120, no. 6, pp. 917-923. https://doi.org/10.1016/j.amjcard.2017.06.019

Quantifying Ischemic Risk After Percutaneous Coronary Intervention Attributable to High Platelet Reactivity on Clopidogrel (From the Assessment of Dual Antiplatelet Therapy with Drug-Eluting Stents Study). / Redfors, Björn; Ben-Yehuda, Ori; Lin, Sheng Hsuan; Furer, Ariel; Kirtane, Ajay J.; Witzenbichler, Bernhard; Weisz, Giora; Stuckey, Thomas D.; Maehara, Akiko; Genereux, Philippe; Giustino, Gennaro; Rinaldi, Michael J.; Neumann, Franz Josef; Metzger, D. Christopher; Henry, Timothy D.; Cox, David A.; Duffy, Peter L.; Mazzaferri, Ernest L.; Ayele, Girma Minalu; Mehran, Roxana; Mintz, Gary S.; Stone, Gregg W.

In: American Journal of Cardiology, Vol. 120, No. 6, 15.09.2017, p. 917-923.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Quantifying Ischemic Risk After Percutaneous Coronary Intervention Attributable to High Platelet Reactivity on Clopidogrel (From the Assessment of Dual Antiplatelet Therapy with Drug-Eluting Stents Study)

AU - Redfors, Björn

AU - Ben-Yehuda, Ori

AU - Lin, Sheng Hsuan

AU - Furer, Ariel

AU - Kirtane, Ajay J.

AU - Witzenbichler, Bernhard

AU - Weisz, Giora

AU - Stuckey, Thomas D.

AU - Maehara, Akiko

AU - Genereux, Philippe

AU - Giustino, Gennaro

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 - Mazzaferri, Ernest L.

AU - Ayele, Girma Minalu

AU - Mehran, Roxana

AU - Mintz, Gary S.

AU - Stone, Gregg W.

PY - 2017/9/15

Y1 - 2017/9/15

N2 - Patients at high risk of thrombotic events after percutaneous coronary intervention (PCI) may potentially benefit from intensified antiplatelet therapy. However, more potent antiplatelet therapy would be expected to only overcome risk that is mediated by high platelet reactivity (PR). We used mediation analysis to determine the contribution of residual PR to the 2-year risk of major adverse cardiac events (MACE; the composite of cardiac death, myocardial infarction, or stent thrombosis) associated with clinical risk factors after PCI with drug-eluting stents (DES) in 8,374 patients from the prospective, multicenter Assessment of Dual AntiPlatelet Therapy with Drug-Eluting Stents (ADAPT-DES) registry. Residual PR on clopidogrel, as measured by the VerifyNow P2Y12 point-of-care assay, was included as a continuous linear mediator variable in Cox proportional hazards regression. Among 7 factors independently associated with 2-year MACE, residual PR partly mediated the effect of diabetes (13.4% attributable risk), anemia (22.9% attributable risk), and acute coronary syndromes (7.3% attributable risk). A PR-mediated effect inversely affected the MACE risk associated with smoking (10.4% attributable risk). The increased ischemic risk of chronic kidney disease, multivessel disease, and previous myocardial infarction were not mediated by residual PR. In conclusion, high residual PR mediates little or none of the increased 2-year MACE risk associated with baseline risk factors in patients treated with clopidogrel after successful PCI with DES. Intensifying antiplatelet therapy is therefore unlikely to substantially mitigate the excess ischemic risk from these variables.

AB - Patients at high risk of thrombotic events after percutaneous coronary intervention (PCI) may potentially benefit from intensified antiplatelet therapy. However, more potent antiplatelet therapy would be expected to only overcome risk that is mediated by high platelet reactivity (PR). We used mediation analysis to determine the contribution of residual PR to the 2-year risk of major adverse cardiac events (MACE; the composite of cardiac death, myocardial infarction, or stent thrombosis) associated with clinical risk factors after PCI with drug-eluting stents (DES) in 8,374 patients from the prospective, multicenter Assessment of Dual AntiPlatelet Therapy with Drug-Eluting Stents (ADAPT-DES) registry. Residual PR on clopidogrel, as measured by the VerifyNow P2Y12 point-of-care assay, was included as a continuous linear mediator variable in Cox proportional hazards regression. Among 7 factors independently associated with 2-year MACE, residual PR partly mediated the effect of diabetes (13.4% attributable risk), anemia (22.9% attributable risk), and acute coronary syndromes (7.3% attributable risk). A PR-mediated effect inversely affected the MACE risk associated with smoking (10.4% attributable risk). The increased ischemic risk of chronic kidney disease, multivessel disease, and previous myocardial infarction were not mediated by residual PR. In conclusion, high residual PR mediates little or none of the increased 2-year MACE risk associated with baseline risk factors in patients treated with clopidogrel after successful PCI with DES. Intensifying antiplatelet therapy is therefore unlikely to substantially mitigate the excess ischemic risk from these variables.

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