Optimizing P2Y12 receptor inhibition in patients with acute coronary syndrome on the basis of platelet function testing: Impact of prasugrel and high-dose clopidogrel

D. Aradi, Adrienn Tornyos, Tünde Pintér, András Vorobcsuk, Attila Kónyi, József Faluközy, Gábor Veress, Balázs Magyari, I. Horváth, A. Komócsi

Research output: Contribution to journalArticle

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Abstract

Objectives: This study sought to evaluate the impact of treatment with prasugrel and high-dose clopidogrel on the basis of platelet function testing in patients with acute coronary syndrome (ACS) who are undergoing percutaneous coronary intervention (PCI). Background: The clinical impact of treatment with prasugrel in patients with ACS who have high platelet reactivity (HPR) is unknown. Methods: Patients with ACS who were pre-treated with clopidogrel and undergoing successful PCI were enrolled in a single-center, prospective registry. Platelet function was measured 12 to 36 h after PCI with the Multiplate device (Roche Diagnostics GmbH, Mannheim, Germany). Patients with HPR (>46 U) were switched to prasugrel or treated with high-dose clopidogrel, and those without HPR continued treatment with 75 mg of clopidogrel. Results: A total of 741 consecutive patients were enrolled in the study between September 2011 and August 2012, and 219 of these patients (29.5%) had HPR. Although platelet reactivity decreased after treatment adjustments in those with HPR, prasugrel provided significantly more potent platelet inhibition compared with high-dose clopidogrel (p <0.0001). Compared with patients without HPR, the risk of all-cause death, myocardial infarction, stent thrombosis, or stroke at 1 year was significantly higher in the high-dose clopidogrel group (hazard ratio [HR]: 2.27; 95% confidence interval [CI]: 1.45 to 3.55; p <0.0001), and patients who were switched to prasugrel had similar outcomes (HR: 0.90; 95% CI: 0.44 to 1.81; p = 0.76). Bleeding Academic Research Consortium (BARC) type 3/5 bleeding was also more frequent in patients treated with high-dose clopidogrel (HR: 2.09; 95% CI: 1.05 to 4.17; p = 0.04) than in patients switched to prasugrel (HR: 0.45; 95% CI: 0.11 to 1.91; p = 0.28). In a multivariate model, HPR with high-dose clopidogrel, but not with prasugrel, was an independent predictor of the composite ischemic endpoint (HR: 1.90; 95% CI: 1.17 to 3.08; p = 0.01). Conclusions: Switching patients with ACS who have HPR to treatment with prasugrel reduces thrombotic and bleeding events to a level similar to that of those without HPR; however, there is a higher risk of both thrombotic and bleeding complications with high-dose clopidogrel.

Original languageEnglish
Pages (from-to)1061-1070
Number of pages10
JournalJournal of the American College of Cardiology
Volume63
Issue number11
DOIs
Publication statusPublished - Mar 25 2014

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clopidogrel
Acute Coronary Syndrome
Blood Platelets
Confidence Intervals
Percutaneous Coronary Intervention
Hemorrhage
Prasugrel Hydrochloride

Keywords

  • bleeding
  • high platelet reactivity
  • high-dose clopidogrel
  • mortality
  • PCI
  • platelet function testing
  • prasugrel
  • stent thrombosis

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Optimizing P2Y12 receptor inhibition in patients with acute coronary syndrome on the basis of platelet function testing : Impact of prasugrel and high-dose clopidogrel. / Aradi, D.; Tornyos, Adrienn; Pintér, Tünde; Vorobcsuk, András; Kónyi, Attila; Faluközy, József; Veress, Gábor; Magyari, Balázs; Horváth, I.; Komócsi, A.

In: Journal of the American College of Cardiology, Vol. 63, No. 11, 25.03.2014, p. 1061-1070.

Research output: Contribution to journalArticle

Aradi, D. ; Tornyos, Adrienn ; Pintér, Tünde ; Vorobcsuk, András ; Kónyi, Attila ; Faluközy, József ; Veress, Gábor ; Magyari, Balázs ; Horváth, I. ; Komócsi, A. / Optimizing P2Y12 receptor inhibition in patients with acute coronary syndrome on the basis of platelet function testing : Impact of prasugrel and high-dose clopidogrel. In: Journal of the American College of Cardiology. 2014 ; Vol. 63, No. 11. pp. 1061-1070.
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abstract = "Objectives: This study sought to evaluate the impact of treatment with prasugrel and high-dose clopidogrel on the basis of platelet function testing in patients with acute coronary syndrome (ACS) who are undergoing percutaneous coronary intervention (PCI). Background: The clinical impact of treatment with prasugrel in patients with ACS who have high platelet reactivity (HPR) is unknown. Methods: Patients with ACS who were pre-treated with clopidogrel and undergoing successful PCI were enrolled in a single-center, prospective registry. Platelet function was measured 12 to 36 h after PCI with the Multiplate device (Roche Diagnostics GmbH, Mannheim, Germany). Patients with HPR (>46 U) were switched to prasugrel or treated with high-dose clopidogrel, and those without HPR continued treatment with 75 mg of clopidogrel. Results: A total of 741 consecutive patients were enrolled in the study between September 2011 and August 2012, and 219 of these patients (29.5{\%}) had HPR. Although platelet reactivity decreased after treatment adjustments in those with HPR, prasugrel provided significantly more potent platelet inhibition compared with high-dose clopidogrel (p <0.0001). Compared with patients without HPR, the risk of all-cause death, myocardial infarction, stent thrombosis, or stroke at 1 year was significantly higher in the high-dose clopidogrel group (hazard ratio [HR]: 2.27; 95{\%} confidence interval [CI]: 1.45 to 3.55; p <0.0001), and patients who were switched to prasugrel had similar outcomes (HR: 0.90; 95{\%} CI: 0.44 to 1.81; p = 0.76). Bleeding Academic Research Consortium (BARC) type 3/5 bleeding was also more frequent in patients treated with high-dose clopidogrel (HR: 2.09; 95{\%} CI: 1.05 to 4.17; p = 0.04) than in patients switched to prasugrel (HR: 0.45; 95{\%} CI: 0.11 to 1.91; p = 0.28). In a multivariate model, HPR with high-dose clopidogrel, but not with prasugrel, was an independent predictor of the composite ischemic endpoint (HR: 1.90; 95{\%} CI: 1.17 to 3.08; p = 0.01). Conclusions: Switching patients with ACS who have HPR to treatment with prasugrel reduces thrombotic and bleeding events to a level similar to that of those without HPR; however, there is a higher risk of both thrombotic and bleeding complications with high-dose clopidogrel.",
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TY - JOUR

T1 - Optimizing P2Y12 receptor inhibition in patients with acute coronary syndrome on the basis of platelet function testing

T2 - Impact of prasugrel and high-dose clopidogrel

AU - Aradi, D.

AU - Tornyos, Adrienn

AU - Pintér, Tünde

AU - Vorobcsuk, András

AU - Kónyi, Attila

AU - Faluközy, József

AU - Veress, Gábor

AU - Magyari, Balázs

AU - Horváth, I.

AU - Komócsi, A.

PY - 2014/3/25

Y1 - 2014/3/25

N2 - Objectives: This study sought to evaluate the impact of treatment with prasugrel and high-dose clopidogrel on the basis of platelet function testing in patients with acute coronary syndrome (ACS) who are undergoing percutaneous coronary intervention (PCI). Background: The clinical impact of treatment with prasugrel in patients with ACS who have high platelet reactivity (HPR) is unknown. Methods: Patients with ACS who were pre-treated with clopidogrel and undergoing successful PCI were enrolled in a single-center, prospective registry. Platelet function was measured 12 to 36 h after PCI with the Multiplate device (Roche Diagnostics GmbH, Mannheim, Germany). Patients with HPR (>46 U) were switched to prasugrel or treated with high-dose clopidogrel, and those without HPR continued treatment with 75 mg of clopidogrel. Results: A total of 741 consecutive patients were enrolled in the study between September 2011 and August 2012, and 219 of these patients (29.5%) had HPR. Although platelet reactivity decreased after treatment adjustments in those with HPR, prasugrel provided significantly more potent platelet inhibition compared with high-dose clopidogrel (p <0.0001). Compared with patients without HPR, the risk of all-cause death, myocardial infarction, stent thrombosis, or stroke at 1 year was significantly higher in the high-dose clopidogrel group (hazard ratio [HR]: 2.27; 95% confidence interval [CI]: 1.45 to 3.55; p <0.0001), and patients who were switched to prasugrel had similar outcomes (HR: 0.90; 95% CI: 0.44 to 1.81; p = 0.76). Bleeding Academic Research Consortium (BARC) type 3/5 bleeding was also more frequent in patients treated with high-dose clopidogrel (HR: 2.09; 95% CI: 1.05 to 4.17; p = 0.04) than in patients switched to prasugrel (HR: 0.45; 95% CI: 0.11 to 1.91; p = 0.28). In a multivariate model, HPR with high-dose clopidogrel, but not with prasugrel, was an independent predictor of the composite ischemic endpoint (HR: 1.90; 95% CI: 1.17 to 3.08; p = 0.01). Conclusions: Switching patients with ACS who have HPR to treatment with prasugrel reduces thrombotic and bleeding events to a level similar to that of those without HPR; however, there is a higher risk of both thrombotic and bleeding complications with high-dose clopidogrel.

AB - Objectives: This study sought to evaluate the impact of treatment with prasugrel and high-dose clopidogrel on the basis of platelet function testing in patients with acute coronary syndrome (ACS) who are undergoing percutaneous coronary intervention (PCI). Background: The clinical impact of treatment with prasugrel in patients with ACS who have high platelet reactivity (HPR) is unknown. Methods: Patients with ACS who were pre-treated with clopidogrel and undergoing successful PCI were enrolled in a single-center, prospective registry. Platelet function was measured 12 to 36 h after PCI with the Multiplate device (Roche Diagnostics GmbH, Mannheim, Germany). Patients with HPR (>46 U) were switched to prasugrel or treated with high-dose clopidogrel, and those without HPR continued treatment with 75 mg of clopidogrel. Results: A total of 741 consecutive patients were enrolled in the study between September 2011 and August 2012, and 219 of these patients (29.5%) had HPR. Although platelet reactivity decreased after treatment adjustments in those with HPR, prasugrel provided significantly more potent platelet inhibition compared with high-dose clopidogrel (p <0.0001). Compared with patients without HPR, the risk of all-cause death, myocardial infarction, stent thrombosis, or stroke at 1 year was significantly higher in the high-dose clopidogrel group (hazard ratio [HR]: 2.27; 95% confidence interval [CI]: 1.45 to 3.55; p <0.0001), and patients who were switched to prasugrel had similar outcomes (HR: 0.90; 95% CI: 0.44 to 1.81; p = 0.76). Bleeding Academic Research Consortium (BARC) type 3/5 bleeding was also more frequent in patients treated with high-dose clopidogrel (HR: 2.09; 95% CI: 1.05 to 4.17; p = 0.04) than in patients switched to prasugrel (HR: 0.45; 95% CI: 0.11 to 1.91; p = 0.28). In a multivariate model, HPR with high-dose clopidogrel, but not with prasugrel, was an independent predictor of the composite ischemic endpoint (HR: 1.90; 95% CI: 1.17 to 3.08; p = 0.01). Conclusions: Switching patients with ACS who have HPR to treatment with prasugrel reduces thrombotic and bleeding events to a level similar to that of those without HPR; however, there is a higher risk of both thrombotic and bleeding complications with high-dose clopidogrel.

KW - bleeding

KW - high platelet reactivity

KW - high-dose clopidogrel

KW - mortality

KW - PCI

KW - platelet function testing

KW - prasugrel

KW - stent thrombosis

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