Platelet Reactivity and Risk of Ischemic Stroke After Coronary Drug-Eluting Stent Implantation: From the ADAPT-DES Study

Gennaro Giustino, Björn Redfors, Ajay J. Kirtane, Roxana Mehran, George D. Dangas, Bernhard Witzenbichler, Franz Josef Neumann, Giora Weisz, Philippe Généreux, Akiko Maehara, Thomas McAndrew, Serdar Farhan, Michael J. Rinaldi, D. Christopher Metzger, Timothy D. Henry, David A. Cox, Peter L. Duffy, Ernest L. Mazzaferri, Bruce R. Brodie, Thomas D. StuckeyPaul Gurbel, Ori Ben-Yehuda, Gregg W. Stone

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Objectives: The authors sought to investigate the association between P2Y12 reaction units (PRU) and the risk of ischemic stroke (IS) after successful coronary drug-eluting stents (DES) implantation. Background: The association between platelet reactivity on clopidogrel and the risk for ischemic cerebrovascular events remains unclear. Methods: Incidence, predictors, and prognostic impact of IS were evaluated among patients enrolled in the multicenter, prospective ADAPT-DES (Assessment of Dual AntiPlatelet Therapy With Drug Eluting Stents) study. By protocol, patients were maintained on aspirin for 2 years and clopidogrel for at least 1 year. Baseline platelet reactivity on clopidogrel and aspirin were assessed by means of VerifyNow point-of-care assay after successful DES implantation. Results: Among 8,582 patients enrolled, 68 (0.8%) had an IS during 2-year follow-up. Across the spectrum of PRU, rates of IS were progressively greater as patients transitioned from the lowest quintile of PRU (more P2Y12 receptor inhibition; 2-year rate of 0.51%) to the highest quintile of PRU (less P2Y12 receptor inhibition; 2-year rate of 1.34%; adjusted p = 0.04). PRU >208 was independently associated with higher risk of IS at 2 years (adjusted hazard ratio 1.81; 95% confidence interval 1.08 to 3.04; p = 0.03). The association between higher PRU and risk for IS was also consistent in patients with versus without high CHA2DS2-VASc score (pinteraction = 0.30) and in those on or off oral anticoagulation at discharge (pinteraction = 0.99). Occurrence of IS was strongly associated with increased risk of all-cause mortality at 2 years (adjusted HR: 4.16; 95% CI: 1.95 to 8.87; p < 0.0001). Conclusions: Higher PRU was associated with increased risk of IS after coronary DES implantation. Ensuring adequate platelet P2Y12 receptor inhibition may reduce the risk of IS in this patient population. (Assessment of Dual AntiPlatelet Therapy With Drug Eluting Stents [ADAPT-DES]; NCT00638794)

Original languageEnglish (US)
Pages (from-to)1277-1286
Number of pages10
JournalJACC: Cardiovascular Interventions
Volume11
Issue number13
DOIs
StatePublished - Jul 9 2018

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Drug-Eluting Stents
Blood Platelets
clopidogrel
Stroke
Therapeutics
Aspirin
Point-of-Care Systems
Confidence Intervals
Mortality
Incidence

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

Cite this

Giustino, G., Redfors, B., Kirtane, A. J., Mehran, R., Dangas, G. D., Witzenbichler, B., ... Stone, G. W. (2018). Platelet Reactivity and Risk of Ischemic Stroke After Coronary Drug-Eluting Stent Implantation: From the ADAPT-DES Study. JACC: Cardiovascular Interventions, 11(13), 1277-1286. https://doi.org/10.1016/j.jcin.2018.01.263
Giustino, Gennaro ; Redfors, Björn ; Kirtane, Ajay J. ; Mehran, Roxana ; Dangas, George D. ; Witzenbichler, Bernhard ; Neumann, Franz Josef ; Weisz, Giora ; Généreux, Philippe ; Maehara, Akiko ; McAndrew, Thomas ; Farhan, Serdar ; Rinaldi, Michael J. ; Metzger, D. Christopher ; Henry, Timothy D. ; Cox, David A. ; Duffy, Peter L. ; Mazzaferri, Ernest L. ; Brodie, Bruce R. ; Stuckey, Thomas D. ; Gurbel, Paul ; Ben-Yehuda, Ori ; Stone, Gregg W. / Platelet Reactivity and Risk of Ischemic Stroke After Coronary Drug-Eluting Stent Implantation : From the ADAPT-DES Study. In: JACC: Cardiovascular Interventions. 2018 ; Vol. 11, No. 13. pp. 1277-1286.
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title = "Platelet Reactivity and Risk of Ischemic Stroke After Coronary Drug-Eluting Stent Implantation: From the ADAPT-DES Study",
abstract = "Objectives: The authors sought to investigate the association between P2Y12 reaction units (PRU) and the risk of ischemic stroke (IS) after successful coronary drug-eluting stents (DES) implantation. Background: The association between platelet reactivity on clopidogrel and the risk for ischemic cerebrovascular events remains unclear. Methods: Incidence, predictors, and prognostic impact of IS were evaluated among patients enrolled in the multicenter, prospective ADAPT-DES (Assessment of Dual AntiPlatelet Therapy With Drug Eluting Stents) study. By protocol, patients were maintained on aspirin for 2 years and clopidogrel for at least 1 year. Baseline platelet reactivity on clopidogrel and aspirin were assessed by means of VerifyNow point-of-care assay after successful DES implantation. Results: Among 8,582 patients enrolled, 68 (0.8{\%}) had an IS during 2-year follow-up. Across the spectrum of PRU, rates of IS were progressively greater as patients transitioned from the lowest quintile of PRU (more P2Y12 receptor inhibition; 2-year rate of 0.51{\%}) to the highest quintile of PRU (less P2Y12 receptor inhibition; 2-year rate of 1.34{\%}; adjusted p = 0.04). PRU >208 was independently associated with higher risk of IS at 2 years (adjusted hazard ratio 1.81; 95{\%} confidence interval 1.08 to 3.04; p = 0.03). The association between higher PRU and risk for IS was also consistent in patients with versus without high CHA2DS2-VASc score (pinteraction = 0.30) and in those on or off oral anticoagulation at discharge (pinteraction = 0.99). Occurrence of IS was strongly associated with increased risk of all-cause mortality at 2 years (adjusted HR: 4.16; 95{\%} CI: 1.95 to 8.87; p < 0.0001). Conclusions: Higher PRU was associated with increased risk of IS after coronary DES implantation. Ensuring adequate platelet P2Y12 receptor inhibition may reduce the risk of IS in this patient population. (Assessment of Dual AntiPlatelet Therapy With Drug Eluting Stents [ADAPT-DES]; NCT00638794)",
author = "Gennaro Giustino and Bj{\"o}rn Redfors and Kirtane, {Ajay J.} and Roxana Mehran and Dangas, {George D.} and Bernhard Witzenbichler and Neumann, {Franz Josef} and Giora Weisz and Philippe G{\'e}n{\'e}reux and Akiko Maehara and Thomas McAndrew and Serdar Farhan and Rinaldi, {Michael J.} and Metzger, {D. Christopher} 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 Paul Gurbel and Ori Ben-Yehuda and Stone, {Gregg W.}",
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Giustino, G, Redfors, B, Kirtane, AJ, Mehran, R, Dangas, GD, Witzenbichler, B, Neumann, FJ, Weisz, G, Généreux, P, Maehara, A, McAndrew, T, Farhan, S, Rinaldi, MJ, Metzger, DC, Henry, TD, Cox, DA, Duffy, PL, Mazzaferri, EL, Brodie, BR, Stuckey, TD, Gurbel, P, Ben-Yehuda, O & Stone, GW 2018, 'Platelet Reactivity and Risk of Ischemic Stroke After Coronary Drug-Eluting Stent Implantation: From the ADAPT-DES Study', JACC: Cardiovascular Interventions, vol. 11, no. 13, pp. 1277-1286. https://doi.org/10.1016/j.jcin.2018.01.263

Platelet Reactivity and Risk of Ischemic Stroke After Coronary Drug-Eluting Stent Implantation : From the ADAPT-DES Study. / Giustino, Gennaro; Redfors, Björn; Kirtane, Ajay J.; Mehran, Roxana; Dangas, George D.; Witzenbichler, Bernhard; Neumann, Franz Josef; Weisz, Giora; Généreux, Philippe; Maehara, Akiko; McAndrew, Thomas; Farhan, Serdar; Rinaldi, Michael J.; Metzger, D. Christopher; Henry, Timothy D.; Cox, David A.; Duffy, Peter L.; Mazzaferri, Ernest L.; Brodie, Bruce R.; Stuckey, Thomas D.; Gurbel, Paul; Ben-Yehuda, Ori; Stone, Gregg W.

In: JACC: Cardiovascular Interventions, Vol. 11, No. 13, 09.07.2018, p. 1277-1286.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Platelet Reactivity and Risk of Ischemic Stroke After Coronary Drug-Eluting Stent Implantation

T2 - From the ADAPT-DES Study

AU - Giustino, Gennaro

AU - Redfors, Björn

AU - Kirtane, Ajay J.

AU - Mehran, Roxana

AU - Dangas, George D.

AU - Witzenbichler, Bernhard

AU - Neumann, Franz Josef

AU - Weisz, Giora

AU - Généreux, Philippe

AU - Maehara, Akiko

AU - McAndrew, Thomas

AU - Farhan, Serdar

AU - Rinaldi, Michael J.

AU - Metzger, D. Christopher

AU - Henry, Timothy D.

AU - Cox, David A.

AU - Duffy, Peter L.

AU - Mazzaferri, Ernest L.

AU - Brodie, Bruce R.

AU - Stuckey, Thomas D.

AU - Gurbel, Paul

AU - Ben-Yehuda, Ori

AU - Stone, Gregg W.

PY - 2018/7/9

Y1 - 2018/7/9

N2 - Objectives: The authors sought to investigate the association between P2Y12 reaction units (PRU) and the risk of ischemic stroke (IS) after successful coronary drug-eluting stents (DES) implantation. Background: The association between platelet reactivity on clopidogrel and the risk for ischemic cerebrovascular events remains unclear. Methods: Incidence, predictors, and prognostic impact of IS were evaluated among patients enrolled in the multicenter, prospective ADAPT-DES (Assessment of Dual AntiPlatelet Therapy With Drug Eluting Stents) study. By protocol, patients were maintained on aspirin for 2 years and clopidogrel for at least 1 year. Baseline platelet reactivity on clopidogrel and aspirin were assessed by means of VerifyNow point-of-care assay after successful DES implantation. Results: Among 8,582 patients enrolled, 68 (0.8%) had an IS during 2-year follow-up. Across the spectrum of PRU, rates of IS were progressively greater as patients transitioned from the lowest quintile of PRU (more P2Y12 receptor inhibition; 2-year rate of 0.51%) to the highest quintile of PRU (less P2Y12 receptor inhibition; 2-year rate of 1.34%; adjusted p = 0.04). PRU >208 was independently associated with higher risk of IS at 2 years (adjusted hazard ratio 1.81; 95% confidence interval 1.08 to 3.04; p = 0.03). The association between higher PRU and risk for IS was also consistent in patients with versus without high CHA2DS2-VASc score (pinteraction = 0.30) and in those on or off oral anticoagulation at discharge (pinteraction = 0.99). Occurrence of IS was strongly associated with increased risk of all-cause mortality at 2 years (adjusted HR: 4.16; 95% CI: 1.95 to 8.87; p < 0.0001). Conclusions: Higher PRU was associated with increased risk of IS after coronary DES implantation. Ensuring adequate platelet P2Y12 receptor inhibition may reduce the risk of IS in this patient population. (Assessment of Dual AntiPlatelet Therapy With Drug Eluting Stents [ADAPT-DES]; NCT00638794)

AB - Objectives: The authors sought to investigate the association between P2Y12 reaction units (PRU) and the risk of ischemic stroke (IS) after successful coronary drug-eluting stents (DES) implantation. Background: The association between platelet reactivity on clopidogrel and the risk for ischemic cerebrovascular events remains unclear. Methods: Incidence, predictors, and prognostic impact of IS were evaluated among patients enrolled in the multicenter, prospective ADAPT-DES (Assessment of Dual AntiPlatelet Therapy With Drug Eluting Stents) study. By protocol, patients were maintained on aspirin for 2 years and clopidogrel for at least 1 year. Baseline platelet reactivity on clopidogrel and aspirin were assessed by means of VerifyNow point-of-care assay after successful DES implantation. Results: Among 8,582 patients enrolled, 68 (0.8%) had an IS during 2-year follow-up. Across the spectrum of PRU, rates of IS were progressively greater as patients transitioned from the lowest quintile of PRU (more P2Y12 receptor inhibition; 2-year rate of 0.51%) to the highest quintile of PRU (less P2Y12 receptor inhibition; 2-year rate of 1.34%; adjusted p = 0.04). PRU >208 was independently associated with higher risk of IS at 2 years (adjusted hazard ratio 1.81; 95% confidence interval 1.08 to 3.04; p = 0.03). The association between higher PRU and risk for IS was also consistent in patients with versus without high CHA2DS2-VASc score (pinteraction = 0.30) and in those on or off oral anticoagulation at discharge (pinteraction = 0.99). Occurrence of IS was strongly associated with increased risk of all-cause mortality at 2 years (adjusted HR: 4.16; 95% CI: 1.95 to 8.87; p < 0.0001). Conclusions: Higher PRU was associated with increased risk of IS after coronary DES implantation. Ensuring adequate platelet P2Y12 receptor inhibition may reduce the risk of IS in this patient population. (Assessment of Dual AntiPlatelet Therapy With Drug Eluting Stents [ADAPT-DES]; NCT00638794)

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DO - 10.1016/j.jcin.2018.01.263

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