Is There an Ideal Level of Platelet P2Y12-Receptor Inhibition in Patients Undergoing Percutaneous Coronary Intervention? "window" Analysis from the ADAPT-DES Study (Assessment of Dual AntiPlatelet Therapy with Drug-Eluting Stents)

Ajay J. Kirtane, Puja B. Parikh, Thomas D. Stuckey, Ke Xu, 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, Rupa Parvataneni, Akiko Maehara, Philippe Généreux, Roxana Mehran, Gregg W. Stone

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Objectives This study sought to determine whether there is an ideal level of platelet reactivity (PR) to optimize safety and efficacy within the large multicenter ADAPT-DES (Assessment of Dual AntiPlatelet Therapy With Drug-Eluting Stents) study of 8,582 patients receiving successful drug-eluting stent implantation. Background Patients with high PR on clopidogrel have a greater incidence of adverse ischemic events after stent implantation, whereas low PR may increase bleeding. Due to limited sample size, previous studies have not been able to adjust for differences in baseline characteristics that may confound the relationship of PR and outcomes. Methods In the ADAPT-DES study, routine platelet function testing (VerifyNow) was performed following clopidogrel loading. To characterize the independent association between PR and clinical events, patients were stratified into quintiles of P2Y12 reaction units (PRU). Results The PRU medians of the 5 quintiles were 57, 130, 187, 244, and 317 (most to least inhibited). There was a monotonic association between successively higher PRU quintiles and stent thrombosis, whereas for clinically relevant bleeding, the greatest risk occurred in the lowest PRU quintile, with similar risks across the 4 higher quintiles. These relationships remained significant in fully adjusted multivariable analyses (adjusted hazard ratio [HR] for stent thrombosis in Q5 versus Q1: 2.32; 95% confidence interval [CI]: 1.17 to 4.59; p = 0.02; adjusted HR for clinically relevant bleeding in Q5 versus Q1: 0.61; 95% CI: 0.47 to 0.77; p < 0.001). However, there were no significant independent associations between the level of PRU and mortality. Conclusions In this large observational study, increasing PRU was associated with a monotonic increase in stent thrombosis, whereas bleeding risk was confined to the lowest PRU quintile, suggesting an optimal therapeutic window of platelet inhibition at moderately inhibited PRU. However, there was no demonstrable threshold effect for PRU and mortality in adjusted analyses, perhaps due to the offsetting impact of bleeding and ischemia across the spectrum of platelet inhibition. (Assessment of Dual AntiPlatelet Therapy With Drug-Eluting Stents [ADAPT-DES]; NCT00638794)

Original languageEnglish (US)
Pages (from-to)1978-1987
Number of pages10
JournalJACC: Cardiovascular Interventions
Volume8
Issue number15
DOIs
StatePublished - Dec 28 2015
Externally publishedYes

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Drug-Eluting Stents
Percutaneous Coronary Intervention
Blood Platelets
clopidogrel
Stents
Hemorrhage
Thrombosis
Therapeutics
Confidence Intervals
Mortality
Sample Size
Observational Studies
Ischemia
Safety
Incidence

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

Cite this

Kirtane, Ajay J. ; Parikh, Puja B. ; Stuckey, Thomas D. ; Xu, Ke ; Witzenbichler, Bernhard ; Weisz, Giora ; Rinaldi, Michael J. ; Neumann, Franz Josef ; Metzger, D. Christopher ; Henry, Timothy D. ; Cox, David A. ; Duffy, Peter L. ; Brodie, Bruce R. ; Mazzaferri, Ernest L. ; Parvataneni, Rupa ; Maehara, Akiko ; Généreux, Philippe ; Mehran, Roxana ; Stone, Gregg W. / Is There an Ideal Level of Platelet P2Y12-Receptor Inhibition in Patients Undergoing Percutaneous Coronary Intervention? "window" Analysis from the ADAPT-DES Study (Assessment of Dual AntiPlatelet Therapy with Drug-Eluting Stents). In: JACC: Cardiovascular Interventions. 2015 ; Vol. 8, No. 15. pp. 1978-1987.
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title = "Is There an Ideal Level of Platelet P2Y12-Receptor Inhibition in Patients Undergoing Percutaneous Coronary Intervention? {"}window{"} Analysis from the ADAPT-DES Study (Assessment of Dual AntiPlatelet Therapy with Drug-Eluting Stents)",
abstract = "Objectives This study sought to determine whether there is an ideal level of platelet reactivity (PR) to optimize safety and efficacy within the large multicenter ADAPT-DES (Assessment of Dual AntiPlatelet Therapy With Drug-Eluting Stents) study of 8,582 patients receiving successful drug-eluting stent implantation. Background Patients with high PR on clopidogrel have a greater incidence of adverse ischemic events after stent implantation, whereas low PR may increase bleeding. Due to limited sample size, previous studies have not been able to adjust for differences in baseline characteristics that may confound the relationship of PR and outcomes. Methods In the ADAPT-DES study, routine platelet function testing (VerifyNow) was performed following clopidogrel loading. To characterize the independent association between PR and clinical events, patients were stratified into quintiles of P2Y12 reaction units (PRU). Results The PRU medians of the 5 quintiles were 57, 130, 187, 244, and 317 (most to least inhibited). There was a monotonic association between successively higher PRU quintiles and stent thrombosis, whereas for clinically relevant bleeding, the greatest risk occurred in the lowest PRU quintile, with similar risks across the 4 higher quintiles. These relationships remained significant in fully adjusted multivariable analyses (adjusted hazard ratio [HR] for stent thrombosis in Q5 versus Q1: 2.32; 95{\%} confidence interval [CI]: 1.17 to 4.59; p = 0.02; adjusted HR for clinically relevant bleeding in Q5 versus Q1: 0.61; 95{\%} CI: 0.47 to 0.77; p < 0.001). However, there were no significant independent associations between the level of PRU and mortality. Conclusions In this large observational study, increasing PRU was associated with a monotonic increase in stent thrombosis, whereas bleeding risk was confined to the lowest PRU quintile, suggesting an optimal therapeutic window of platelet inhibition at moderately inhibited PRU. However, there was no demonstrable threshold effect for PRU and mortality in adjusted analyses, perhaps due to the offsetting impact of bleeding and ischemia across the spectrum of platelet inhibition. (Assessment of Dual AntiPlatelet Therapy With Drug-Eluting Stents [ADAPT-DES]; NCT00638794)",
author = "Kirtane, {Ajay J.} and Parikh, {Puja B.} and Stuckey, {Thomas D.} and Ke Xu 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 Rupa Parvataneni and Akiko Maehara and Philippe G{\'e}n{\'e}reux and Roxana Mehran and Stone, {Gregg W.}",
year = "2015",
month = "12",
day = "28",
doi = "10.1016/j.jcin.2015.08.032",
language = "English (US)",
volume = "8",
pages = "1978--1987",
journal = "JACC: Cardiovascular Interventions",
issn = "1936-8798",
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Kirtane, AJ, Parikh, PB, Stuckey, TD, Xu, K, Witzenbichler, B, Weisz, G, Rinaldi, MJ, Neumann, FJ, Metzger, DC, Henry, TD, Cox, DA, Duffy, PL, Brodie, BR, Mazzaferri, EL, Parvataneni, R, Maehara, A, Généreux, P, Mehran, R & Stone, GW 2015, 'Is There an Ideal Level of Platelet P2Y12-Receptor Inhibition in Patients Undergoing Percutaneous Coronary Intervention? "window" Analysis from the ADAPT-DES Study (Assessment of Dual AntiPlatelet Therapy with Drug-Eluting Stents)', JACC: Cardiovascular Interventions, vol. 8, no. 15, pp. 1978-1987. https://doi.org/10.1016/j.jcin.2015.08.032

Is There an Ideal Level of Platelet P2Y12-Receptor Inhibition in Patients Undergoing Percutaneous Coronary Intervention? "window" Analysis from the ADAPT-DES Study (Assessment of Dual AntiPlatelet Therapy with Drug-Eluting Stents). / Kirtane, Ajay J.; Parikh, Puja B.; Stuckey, Thomas D.; Xu, Ke; Witzenbichler, Bernhard; Weisz, Giora; Rinaldi, Michael J.; Neumann, Franz Josef; Metzger, D. Christopher; Henry, Timothy D.; Cox, David A.; Duffy, Peter L.; Brodie, Bruce R.; Mazzaferri, Ernest L.; Parvataneni, Rupa; Maehara, Akiko; Généreux, Philippe; Mehran, Roxana; Stone, Gregg W.

In: JACC: Cardiovascular Interventions, Vol. 8, No. 15, 28.12.2015, p. 1978-1987.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Is There an Ideal Level of Platelet P2Y12-Receptor Inhibition in Patients Undergoing Percutaneous Coronary Intervention? "window" Analysis from the ADAPT-DES Study (Assessment of Dual AntiPlatelet Therapy with Drug-Eluting Stents)

AU - Kirtane, Ajay J.

AU - Parikh, Puja B.

AU - Stuckey, Thomas D.

AU - Xu, Ke

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 - Parvataneni, Rupa

AU - Maehara, Akiko

AU - Généreux, Philippe

AU - Mehran, Roxana

AU - Stone, Gregg W.

PY - 2015/12/28

Y1 - 2015/12/28

N2 - Objectives This study sought to determine whether there is an ideal level of platelet reactivity (PR) to optimize safety and efficacy within the large multicenter ADAPT-DES (Assessment of Dual AntiPlatelet Therapy With Drug-Eluting Stents) study of 8,582 patients receiving successful drug-eluting stent implantation. Background Patients with high PR on clopidogrel have a greater incidence of adverse ischemic events after stent implantation, whereas low PR may increase bleeding. Due to limited sample size, previous studies have not been able to adjust for differences in baseline characteristics that may confound the relationship of PR and outcomes. Methods In the ADAPT-DES study, routine platelet function testing (VerifyNow) was performed following clopidogrel loading. To characterize the independent association between PR and clinical events, patients were stratified into quintiles of P2Y12 reaction units (PRU). Results The PRU medians of the 5 quintiles were 57, 130, 187, 244, and 317 (most to least inhibited). There was a monotonic association between successively higher PRU quintiles and stent thrombosis, whereas for clinically relevant bleeding, the greatest risk occurred in the lowest PRU quintile, with similar risks across the 4 higher quintiles. These relationships remained significant in fully adjusted multivariable analyses (adjusted hazard ratio [HR] for stent thrombosis in Q5 versus Q1: 2.32; 95% confidence interval [CI]: 1.17 to 4.59; p = 0.02; adjusted HR for clinically relevant bleeding in Q5 versus Q1: 0.61; 95% CI: 0.47 to 0.77; p < 0.001). However, there were no significant independent associations between the level of PRU and mortality. Conclusions In this large observational study, increasing PRU was associated with a monotonic increase in stent thrombosis, whereas bleeding risk was confined to the lowest PRU quintile, suggesting an optimal therapeutic window of platelet inhibition at moderately inhibited PRU. However, there was no demonstrable threshold effect for PRU and mortality in adjusted analyses, perhaps due to the offsetting impact of bleeding and ischemia across the spectrum of platelet inhibition. (Assessment of Dual AntiPlatelet Therapy With Drug-Eluting Stents [ADAPT-DES]; NCT00638794)

AB - Objectives This study sought to determine whether there is an ideal level of platelet reactivity (PR) to optimize safety and efficacy within the large multicenter ADAPT-DES (Assessment of Dual AntiPlatelet Therapy With Drug-Eluting Stents) study of 8,582 patients receiving successful drug-eluting stent implantation. Background Patients with high PR on clopidogrel have a greater incidence of adverse ischemic events after stent implantation, whereas low PR may increase bleeding. Due to limited sample size, previous studies have not been able to adjust for differences in baseline characteristics that may confound the relationship of PR and outcomes. Methods In the ADAPT-DES study, routine platelet function testing (VerifyNow) was performed following clopidogrel loading. To characterize the independent association between PR and clinical events, patients were stratified into quintiles of P2Y12 reaction units (PRU). Results The PRU medians of the 5 quintiles were 57, 130, 187, 244, and 317 (most to least inhibited). There was a monotonic association between successively higher PRU quintiles and stent thrombosis, whereas for clinically relevant bleeding, the greatest risk occurred in the lowest PRU quintile, with similar risks across the 4 higher quintiles. These relationships remained significant in fully adjusted multivariable analyses (adjusted hazard ratio [HR] for stent thrombosis in Q5 versus Q1: 2.32; 95% confidence interval [CI]: 1.17 to 4.59; p = 0.02; adjusted HR for clinically relevant bleeding in Q5 versus Q1: 0.61; 95% CI: 0.47 to 0.77; p < 0.001). However, there were no significant independent associations between the level of PRU and mortality. Conclusions In this large observational study, increasing PRU was associated with a monotonic increase in stent thrombosis, whereas bleeding risk was confined to the lowest PRU quintile, suggesting an optimal therapeutic window of platelet inhibition at moderately inhibited PRU. However, there was no demonstrable threshold effect for PRU and mortality in adjusted analyses, perhaps due to the offsetting impact of bleeding and ischemia across the spectrum of platelet inhibition. (Assessment of Dual AntiPlatelet Therapy With Drug-Eluting Stents [ADAPT-DES]; NCT00638794)

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