Comparison of reduced-dose prasugrel and standard-dose clopidogrel in elderly patients with acute coronary syndromes undergoing early percutaneous revascularization

Stefano Savonitto, Luca A. Ferri, Luigi Piatti, Daniele Grosseto, Giancarlo Piovaccari, Nuccia Morici, Irene Bossi, Paolo Sganzerla, Giovanni Tortorella, Michele Cacucci, Maurizio Ferrario, Ernesto Murena, Girolamo Sibilio, Stefano Tondi, Anna Toso, Sergio Bongioanni, Amelia Ravera, Elena Corrada, Matteo Mariani, Leonardo Di AscenzoA. Sonia Petronio, Claudio Cavallini, Giancarlo Vitrella, Renata Rogacka, Roberto Antonicelli, Bruno M. Cesana, Leonardo De Luca, Filippo Ottani, Giuseppe De Luca, Federico Piscione, Nadia Moffa, Stefano De Servi

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

BACKGROUND: Elderly patients are at elevated risk of both ischemic and bleeding complications after an acute coronary syndrome and display higher on-clopidogrel platelet reactivity compared with younger patients. Prasugrel 5 mg provides more predictable platelet inhibition compared with clopidogrel in the elderly, suggesting the possibility of reducing ischemic events without increasing bleeding. METHODS: In a multicenter, randomized, open-label, blinded end point trial, we compared a once-daily maintenance dose of prasugrel 5 mg with the standard clopidogrel 75 mg in patients >74 years of age with acute coronary syndrome undergoing percutaneous coronary intervention. The primary end point was the composite of mortality, myocardial infarction, disabling stroke, and rehospitalization for cardiovascular causes or bleeding within 1 year. The study was designed to demonstrate superiority of prasugrel 5 mg over clopidogrel 75 mg. RESULTS: Enrollment was interrupted, according to prespecified criteria, after a planned interim analysis, when 1443 patients (40% women; mean age, 80 years) had been enrolled with a median follow-up of 12 months, because of futility for efficacy. The primary end point occurred in 121 patients (17%) with prasugrel and 121 (16.6%) with clopidogrel (hazard ratio, 1.007; 95% confidence interval, 0.78-1.30; P=0.955). Definite/ probable stent thrombosis rates were 0.7% with prasugrel versus 1.9% with clopidogrel (odds ratio, 0.36; 95% confidence interval, 0.13-1.00; P=0.06). Bleeding Academic Research Consortium types 2 and greater rates were 4.1% with prasugrel versus 2.7% with clopidogrel (odds ratio, 1.52; 95% confidence interval, 0.85-3.16; P=0.18). CONCLUSIONS: The present study in elderly patients with acute coronary syndromes showed no difference in the primary end point between reduced-dose prasugrel and standard-dose clopidogrel. However, the study should be interpreted in light of the premature termination of the trial.

Original languageEnglish
Pages (from-to)2435-2445
Number of pages11
JournalCirculation
Volume137
Issue number23
DOIs
Publication statusPublished - Jan 1 2018

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clopidogrel
Acute Coronary Syndrome
Hemorrhage
Confidence Intervals
Blood Platelets
Odds Ratio
Myocardial Infarction
Medical Futility
Prasugrel Hydrochloride
Percutaneous Coronary Intervention

Keywords

  • Acute coronary syndrome
  • Aged
  • Percutaneous coronary intervention
  • Platelet aggregation inhibitors

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Comparison of reduced-dose prasugrel and standard-dose clopidogrel in elderly patients with acute coronary syndromes undergoing early percutaneous revascularization. / Savonitto, Stefano; Ferri, Luca A.; Piatti, Luigi; Grosseto, Daniele; Piovaccari, Giancarlo; Morici, Nuccia; Bossi, Irene; Sganzerla, Paolo; Tortorella, Giovanni; Cacucci, Michele; Ferrario, Maurizio; Murena, Ernesto; Sibilio, Girolamo; Tondi, Stefano; Toso, Anna; Bongioanni, Sergio; Ravera, Amelia; Corrada, Elena; Mariani, Matteo; Di Ascenzo, Leonardo; Sonia Petronio, A.; Cavallini, Claudio; Vitrella, Giancarlo; Rogacka, Renata; Antonicelli, Roberto; Cesana, Bruno M.; De Luca, Leonardo; Ottani, Filippo; De Luca, Giuseppe; Piscione, Federico; Moffa, Nadia; De Servi, Stefano.

In: Circulation, Vol. 137, No. 23, 01.01.2018, p. 2435-2445.

Research output: Contribution to journalArticle

Savonitto, S, Ferri, LA, Piatti, L, Grosseto, D, Piovaccari, G, Morici, N, Bossi, I, Sganzerla, P, Tortorella, G, Cacucci, M, Ferrario, M, Murena, E, Sibilio, G, Tondi, S, Toso, A, Bongioanni, S, Ravera, A, Corrada, E, Mariani, M, Di Ascenzo, L, Sonia Petronio, A, Cavallini, C, Vitrella, G, Rogacka, R, Antonicelli, R, Cesana, BM, De Luca, L, Ottani, F, De Luca, G, Piscione, F, Moffa, N & De Servi, S 2018, 'Comparison of reduced-dose prasugrel and standard-dose clopidogrel in elderly patients with acute coronary syndromes undergoing early percutaneous revascularization', Circulation, vol. 137, no. 23, pp. 2435-2445. https://doi.org/10.1161/CIRCULATIONAHA.117.032180
Savonitto, Stefano ; Ferri, Luca A. ; Piatti, Luigi ; Grosseto, Daniele ; Piovaccari, Giancarlo ; Morici, Nuccia ; Bossi, Irene ; Sganzerla, Paolo ; Tortorella, Giovanni ; Cacucci, Michele ; Ferrario, Maurizio ; Murena, Ernesto ; Sibilio, Girolamo ; Tondi, Stefano ; Toso, Anna ; Bongioanni, Sergio ; Ravera, Amelia ; Corrada, Elena ; Mariani, Matteo ; Di Ascenzo, Leonardo ; Sonia Petronio, A. ; Cavallini, Claudio ; Vitrella, Giancarlo ; Rogacka, Renata ; Antonicelli, Roberto ; Cesana, Bruno M. ; De Luca, Leonardo ; Ottani, Filippo ; De Luca, Giuseppe ; Piscione, Federico ; Moffa, Nadia ; De Servi, Stefano. / Comparison of reduced-dose prasugrel and standard-dose clopidogrel in elderly patients with acute coronary syndromes undergoing early percutaneous revascularization. In: Circulation. 2018 ; Vol. 137, No. 23. pp. 2435-2445.
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TY - JOUR

T1 - Comparison of reduced-dose prasugrel and standard-dose clopidogrel in elderly patients with acute coronary syndromes undergoing early percutaneous revascularization

AU - Savonitto, Stefano

AU - Ferri, Luca A.

AU - Piatti, Luigi

AU - Grosseto, Daniele

AU - Piovaccari, Giancarlo

AU - Morici, Nuccia

AU - Bossi, Irene

AU - Sganzerla, Paolo

AU - Tortorella, Giovanni

AU - Cacucci, Michele

AU - Ferrario, Maurizio

AU - Murena, Ernesto

AU - Sibilio, Girolamo

AU - Tondi, Stefano

AU - Toso, Anna

AU - Bongioanni, Sergio

AU - Ravera, Amelia

AU - Corrada, Elena

AU - Mariani, Matteo

AU - Di Ascenzo, Leonardo

AU - Sonia Petronio, A.

AU - Cavallini, Claudio

AU - Vitrella, Giancarlo

AU - Rogacka, Renata

AU - Antonicelli, Roberto

AU - Cesana, Bruno M.

AU - De Luca, Leonardo

AU - Ottani, Filippo

AU - De Luca, Giuseppe

AU - Piscione, Federico

AU - Moffa, Nadia

AU - De Servi, Stefano

PY - 2018/1/1

Y1 - 2018/1/1

N2 - BACKGROUND: Elderly patients are at elevated risk of both ischemic and bleeding complications after an acute coronary syndrome and display higher on-clopidogrel platelet reactivity compared with younger patients. Prasugrel 5 mg provides more predictable platelet inhibition compared with clopidogrel in the elderly, suggesting the possibility of reducing ischemic events without increasing bleeding. METHODS: In a multicenter, randomized, open-label, blinded end point trial, we compared a once-daily maintenance dose of prasugrel 5 mg with the standard clopidogrel 75 mg in patients >74 years of age with acute coronary syndrome undergoing percutaneous coronary intervention. The primary end point was the composite of mortality, myocardial infarction, disabling stroke, and rehospitalization for cardiovascular causes or bleeding within 1 year. The study was designed to demonstrate superiority of prasugrel 5 mg over clopidogrel 75 mg. RESULTS: Enrollment was interrupted, according to prespecified criteria, after a planned interim analysis, when 1443 patients (40% women; mean age, 80 years) had been enrolled with a median follow-up of 12 months, because of futility for efficacy. The primary end point occurred in 121 patients (17%) with prasugrel and 121 (16.6%) with clopidogrel (hazard ratio, 1.007; 95% confidence interval, 0.78-1.30; P=0.955). Definite/ probable stent thrombosis rates were 0.7% with prasugrel versus 1.9% with clopidogrel (odds ratio, 0.36; 95% confidence interval, 0.13-1.00; P=0.06). Bleeding Academic Research Consortium types 2 and greater rates were 4.1% with prasugrel versus 2.7% with clopidogrel (odds ratio, 1.52; 95% confidence interval, 0.85-3.16; P=0.18). CONCLUSIONS: The present study in elderly patients with acute coronary syndromes showed no difference in the primary end point between reduced-dose prasugrel and standard-dose clopidogrel. However, the study should be interpreted in light of the premature termination of the trial.

AB - BACKGROUND: Elderly patients are at elevated risk of both ischemic and bleeding complications after an acute coronary syndrome and display higher on-clopidogrel platelet reactivity compared with younger patients. Prasugrel 5 mg provides more predictable platelet inhibition compared with clopidogrel in the elderly, suggesting the possibility of reducing ischemic events without increasing bleeding. METHODS: In a multicenter, randomized, open-label, blinded end point trial, we compared a once-daily maintenance dose of prasugrel 5 mg with the standard clopidogrel 75 mg in patients >74 years of age with acute coronary syndrome undergoing percutaneous coronary intervention. The primary end point was the composite of mortality, myocardial infarction, disabling stroke, and rehospitalization for cardiovascular causes or bleeding within 1 year. The study was designed to demonstrate superiority of prasugrel 5 mg over clopidogrel 75 mg. RESULTS: Enrollment was interrupted, according to prespecified criteria, after a planned interim analysis, when 1443 patients (40% women; mean age, 80 years) had been enrolled with a median follow-up of 12 months, because of futility for efficacy. The primary end point occurred in 121 patients (17%) with prasugrel and 121 (16.6%) with clopidogrel (hazard ratio, 1.007; 95% confidence interval, 0.78-1.30; P=0.955). Definite/ probable stent thrombosis rates were 0.7% with prasugrel versus 1.9% with clopidogrel (odds ratio, 0.36; 95% confidence interval, 0.13-1.00; P=0.06). Bleeding Academic Research Consortium types 2 and greater rates were 4.1% with prasugrel versus 2.7% with clopidogrel (odds ratio, 1.52; 95% confidence interval, 0.85-3.16; P=0.18). CONCLUSIONS: The present study in elderly patients with acute coronary syndromes showed no difference in the primary end point between reduced-dose prasugrel and standard-dose clopidogrel. However, the study should be interpreted in light of the premature termination of the trial.

KW - Acute coronary syndrome

KW - Aged

KW - Percutaneous coronary intervention

KW - Platelet aggregation inhibitors

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