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Safety and efficacy of prasugrel in East Asian patients with acute coronary syndromes
G Model
JJCC-1537; No. of Pages 2 Journal of Cardiology xxx (2017) xxx–xxx
Contents lists available at ScienceDirect
Journal of Cardiology journal homepage: www.elsevier.com/locate/jjcc
Letter to the Editor Safety and efficacy of prasugrel in East Asian patients with acute coronary syndromes
Keywords: Prasugrel Clopidogrel Acute coronary syndrome Revascularization PCI
Dear Editor, We read with great interest the article by Park et al. [1] titled “Comparison of prasugrel versus clopidogrel in Korean patients with acute myocardial infarction undergoing successful revascularization.” The authors investigated the safety and efficacy of prasugrel in Korean patients with acute myocardial infarction (AMI) undergoing successful revascularization [1]. The authors concluded that the recommended dose of prasugrel had significantly higher in-hospital bleeding complications without reducing ischemic events in comparison to clopidogrel [1]. However, is this true? We performed a thorough search of the literature which resulted in a significant number of recent studies and guideline recommendations demonstrating the safety and efficacy of prasugrel in East Asian patients with acute coronary syndromes (ACS) [2–5]. A multicenter, double-blind, randomized study by Saito et al. demonstrated that prasugrel administered at the adjusted dose is associated with a low incidence of major adverse cardiac events (cardiovascular death, non-fatal MI, and non-fatal ischemic stroke) [2]. The incidence of major events at 24 weeks was 9.4% in the prasugrel group and 11.8% in the clopidogrel group and the incidence of major bleeding was similar in the two groups (1.9% vs. 2.2% at 24 weeks) [2]. Furthermore, in the high bleeding risk group of patients aged 75 years or weighing 60 kg, the percentage of bleeding complications was also comparable between groups [2]. Lee et al. in a double-blind, prospective study verified the efficacy of platelet inhibition by the recommended dose of prasugrel in Korean patients with ST-segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI) [3]. Lee et al. also did not observe adverse events or side effects in the prasugrel group during the 30-day follow-up period [3]. Nishikawa et al. in a review of current published data and new analyses of the trials of patients undergoing PCI for ACS concluded that the bleeding risk with prasugrel was the same with the standard dose of clopidogrel, including bleeding events re-classified
using the Bleeding Academic Research Consortium criteria [4]. The post hoc analyses revealed no relationship between the pharmacodynamics of prasugrel and the risk of bleeding events [4]. The study [1] has methodological flaws such as the use of femoral access artery and the use of glycoprotein IIb/IIIa inhibitors, which may have influenced the results. The risk of bleeding during PCI could be reduced using a radial access artery rather than a femoral access artery and the use of glycoprotein IIb/IIIa inhibitors in STEMI patients has no clinical benefit [4,5]. The South Korean guidelines for antiplatelet therapy in patients with ACS mostly parallel recommendations in the European Society of Cardiology (ESC) and American Heart Association/American College of Cardiology (ACC/AHA) guidelines on antiplatelet therapy [5]. The guidelines recommend the use of prasugrel (Class I, level of evidence B) in patients undergoing primary PCI, as has proven to be associated with a lower number of recurrences of ACS or death compared to clopidogrel [5]. The ‘East Asian paradox’ describes a phenomenon in which, despite an increased level of platelet reactivity during treatment with clopidogrel, East Asian patients have a similar or even lower rate of ischemic events after PCI compared with Caucasian patients [5]. The slow onset of action of clopidogrel could be actually harmful in clinical practice of ACS treatment and several patients complicated by stent thrombosis might be poor metabolizers of CYP2C19 substrates, carrying genetic polymorphisms. Prasugrel has a much faster onset and a more potent antiplatelet inhibition and is currently a first-line agent in ACS patients. We agree that further large-scale prospective randomized clinical studies are required before we can actually identify the optimal dose of prasugrel in East Asian patients with ACS. Conflict of interest None declared. References [1] Park KH, Jeong MH, Kim HK, Ahn TH, Seung KB, Oh DJ, Choi DJ, Kim HS, Gwon HC, Seong IW, Hwang KK, Chae SC, Kim KB, Kim YJ, Cha KS, et al. Comparison of prasugrel versus clopidogrel in Korean patients with acute myocardial infarction undergoing successful revascularization. J Cardiol 2017;69:272–9. [2] Saito S, Isshiki T, Kimura T, Ogawa H, Yokoi H, Nanto S, Takayama M, Kitagawa K, Nishikawa M, Miyazaki S, Nakamura M. Efficacy and safety of adjusted-dose prasugrel compared with clopidogrel in Japanese patients with acute coronary syndrome: the PRASFIT-ACS study. Circ J 2014;78:1684–92. [3] Lee YS, Jin CD, Kim MH, Guo LZ, Cho YR, Park K, Park JS, Park TH, Kim YD. Comparison of prasugrel and ticagrelor antiplatelet effects in Korean patients presenting with ST-segment elevation myocardial infarction. Circ J 2015;79:1248–54. [4] Nishikawa M, Isshiki T, Kimura T, Ogawa H, Yokoi H, Miyazaki S, Ikeda Y, Nakamura M, Tanaka Y, Saito S. Risk of bleeding and repeated bleeding events in prasugrel-treated patients: a review of data from the Japanese PRASFIT studies. Cardiovasc Interv Ther 2017;32:93–105. [5] Levine GN, Jeong YH, Goto S, Anderson JL, Huo Y, Mega JL, Taubert K, Smith Jr SC. Expert consensus document: World Heart Federation expert consensus statement on antiplatelet therapy in East Asian patients with ACS or undergoing PCI. Nat Rev Cardiol 2014;11:597–606.
http://dx.doi.org/10.1016/j.jjcc.2017.07.016 0914-5087/© 2017 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.
Please cite this article in press as: Spartalis M, et al. Safety and efficacy of prasugrel in East Asian patients with acute coronary syndromes. J Cardiol (2017), http://dx.doi.org/10.1016/j.jjcc.2017.07.016
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JJCC-1537; No. of Pages 2 2
Letter to the Editor / Journal of Cardiology xxx (2017) xxx–xxx
Michael Spartalis (MD, MSc, PhD)* Eleni Tzatzaki (MD, PhD) Division of Cardiology, Onassis Cardiac Surgery Center, Athens, Greece Antonios Athanasiou (MD, MSc, PhD) Department of Surgery, Mercy University Hospital, Cork, Ireland
EleniTzatzaki(MD, PhD) *Corresponding author at: Fokidos 42, Athens 115 27, Greece E-mail address: [email protected] (M. Spartalis). Received 6 July 2017
Please cite this article in press as: Spartalis M, et al. Safety and efficacy of prasugrel in East Asian patients with acute coronary syndromes. J Cardiol (2017), http://dx.doi.org/10.1016/j.jjcc.2017.07.016
JJCC-1537; No. of Pages 2 Journal of Cardiology xxx (2017) xxx–xxx
Contents lists available at ScienceDirect
Journal of Cardiology journal homepage: www.elsevier.com/locate/jjcc
Letter to the Editor Safety and efficacy of prasugrel in East Asian patients with acute coronary syndromes
Keywords: Prasugrel Clopidogrel Acute coronary syndrome Revascularization PCI
Dear Editor, We read with great interest the article by Park et al. [1] titled “Comparison of prasugrel versus clopidogrel in Korean patients with acute myocardial infarction undergoing successful revascularization.” The authors investigated the safety and efficacy of prasugrel in Korean patients with acute myocardial infarction (AMI) undergoing successful revascularization [1]. The authors concluded that the recommended dose of prasugrel had significantly higher in-hospital bleeding complications without reducing ischemic events in comparison to clopidogrel [1]. However, is this true? We performed a thorough search of the literature which resulted in a significant number of recent studies and guideline recommendations demonstrating the safety and efficacy of prasugrel in East Asian patients with acute coronary syndromes (ACS) [2–5]. A multicenter, double-blind, randomized study by Saito et al. demonstrated that prasugrel administered at the adjusted dose is associated with a low incidence of major adverse cardiac events (cardiovascular death, non-fatal MI, and non-fatal ischemic stroke) [2]. The incidence of major events at 24 weeks was 9.4% in the prasugrel group and 11.8% in the clopidogrel group and the incidence of major bleeding was similar in the two groups (1.9% vs. 2.2% at 24 weeks) [2]. Furthermore, in the high bleeding risk group of patients aged 75 years or weighing 60 kg, the percentage of bleeding complications was also comparable between groups [2]. Lee et al. in a double-blind, prospective study verified the efficacy of platelet inhibition by the recommended dose of prasugrel in Korean patients with ST-segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI) [3]. Lee et al. also did not observe adverse events or side effects in the prasugrel group during the 30-day follow-up period [3]. Nishikawa et al. in a review of current published data and new analyses of the trials of patients undergoing PCI for ACS concluded that the bleeding risk with prasugrel was the same with the standard dose of clopidogrel, including bleeding events re-classified
using the Bleeding Academic Research Consortium criteria [4]. The post hoc analyses revealed no relationship between the pharmacodynamics of prasugrel and the risk of bleeding events [4]. The study [1] has methodological flaws such as the use of femoral access artery and the use of glycoprotein IIb/IIIa inhibitors, which may have influenced the results. The risk of bleeding during PCI could be reduced using a radial access artery rather than a femoral access artery and the use of glycoprotein IIb/IIIa inhibitors in STEMI patients has no clinical benefit [4,5]. The South Korean guidelines for antiplatelet therapy in patients with ACS mostly parallel recommendations in the European Society of Cardiology (ESC) and American Heart Association/American College of Cardiology (ACC/AHA) guidelines on antiplatelet therapy [5]. The guidelines recommend the use of prasugrel (Class I, level of evidence B) in patients undergoing primary PCI, as has proven to be associated with a lower number of recurrences of ACS or death compared to clopidogrel [5]. The ‘East Asian paradox’ describes a phenomenon in which, despite an increased level of platelet reactivity during treatment with clopidogrel, East Asian patients have a similar or even lower rate of ischemic events after PCI compared with Caucasian patients [5]. The slow onset of action of clopidogrel could be actually harmful in clinical practice of ACS treatment and several patients complicated by stent thrombosis might be poor metabolizers of CYP2C19 substrates, carrying genetic polymorphisms. Prasugrel has a much faster onset and a more potent antiplatelet inhibition and is currently a first-line agent in ACS patients. We agree that further large-scale prospective randomized clinical studies are required before we can actually identify the optimal dose of prasugrel in East Asian patients with ACS. Conflict of interest None declared. References [1] Park KH, Jeong MH, Kim HK, Ahn TH, Seung KB, Oh DJ, Choi DJ, Kim HS, Gwon HC, Seong IW, Hwang KK, Chae SC, Kim KB, Kim YJ, Cha KS, et al. Comparison of prasugrel versus clopidogrel in Korean patients with acute myocardial infarction undergoing successful revascularization. J Cardiol 2017;69:272–9. [2] Saito S, Isshiki T, Kimura T, Ogawa H, Yokoi H, Nanto S, Takayama M, Kitagawa K, Nishikawa M, Miyazaki S, Nakamura M. Efficacy and safety of adjusted-dose prasugrel compared with clopidogrel in Japanese patients with acute coronary syndrome: the PRASFIT-ACS study. Circ J 2014;78:1684–92. [3] Lee YS, Jin CD, Kim MH, Guo LZ, Cho YR, Park K, Park JS, Park TH, Kim YD. Comparison of prasugrel and ticagrelor antiplatelet effects in Korean patients presenting with ST-segment elevation myocardial infarction. Circ J 2015;79:1248–54. [4] Nishikawa M, Isshiki T, Kimura T, Ogawa H, Yokoi H, Miyazaki S, Ikeda Y, Nakamura M, Tanaka Y, Saito S. Risk of bleeding and repeated bleeding events in prasugrel-treated patients: a review of data from the Japanese PRASFIT studies. Cardiovasc Interv Ther 2017;32:93–105. [5] Levine GN, Jeong YH, Goto S, Anderson JL, Huo Y, Mega JL, Taubert K, Smith Jr SC. Expert consensus document: World Heart Federation expert consensus statement on antiplatelet therapy in East Asian patients with ACS or undergoing PCI. Nat Rev Cardiol 2014;11:597–606.
http://dx.doi.org/10.1016/j.jjcc.2017.07.016 0914-5087/© 2017 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.
Please cite this article in press as: Spartalis M, et al. Safety and efficacy of prasugrel in East Asian patients with acute coronary syndromes. J Cardiol (2017), http://dx.doi.org/10.1016/j.jjcc.2017.07.016
G Model
JJCC-1537; No. of Pages 2 2
Letter to the Editor / Journal of Cardiology xxx (2017) xxx–xxx
Michael Spartalis (MD, MSc, PhD)* Eleni Tzatzaki (MD, PhD) Division of Cardiology, Onassis Cardiac Surgery Center, Athens, Greece Antonios Athanasiou (MD, MSc, PhD) Department of Surgery, Mercy University Hospital, Cork, Ireland
EleniTzatzaki(MD, PhD) *Corresponding author at: Fokidos 42, Athens 115 27, Greece E-mail address: [email protected] (M. Spartalis). Received 6 July 2017
Please cite this article in press as: Spartalis M, et al. Safety and efficacy of prasugrel in East Asian patients with acute coronary syndromes. J Cardiol (2017), http://dx.doi.org/10.1016/j.jjcc.2017.07.016