Comparison of Reduced-Dose Prasugrel and Standard-Dose Clopidogrel in Elderly Patients With Acute Coronary Syndromes Undergoing Early Percutaneous Revascularization

Elderly ACS-2 Investigators

Research output: Contribution to journalArticle

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.

CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01777503.

Original languageEnglish
Pages (from-to)2435-2445
Number of pages11
JournalCirculation
Volume137
Issue number23
DOIs
Publication statusPublished - Jun 5 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

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Comparison of Reduced-Dose Prasugrel and Standard-Dose Clopidogrel in Elderly Patients With Acute Coronary Syndromes Undergoing Early Percutaneous Revascularization. / Elderly ACS-2 Investigators.

In: Circulation, Vol. 137, No. 23, 05.06.2018, p. 2435-2445.

Research output: Contribution to journalArticle

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title = "Comparison of Reduced-Dose Prasugrel and Standard-Dose Clopidogrel in Elderly Patients With Acute Coronary Syndromes Undergoing Early Percutaneous Revascularization",
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.CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01777503.",
author = "{Elderly ACS-2 Investigators} and Stefano Savonitto and Ferri, {Luca A} and Luigi Piatti and Daniele Grosseto and Giancarlo Piovaccari and Nuccia Morici and Irene Bossi and Paolo Sganzerla and Giovanni Tortorella and Michele Cacucci and Maurizio Ferrario and Ernesto Murena and Girolamo Sibilio and Stefano Tondi and Anna Toso and Sergio Bongioanni and Amelia Ravera and Elena Corrada and Matteo Mariani and {Di Ascenzo}, Leonardo and Petronio, {A Sonia} and Claudio Cavallini and Giancarlo Vitrella and Renata Rogacka and Roberto Antonicelli and Cesana, {Bruno M} and {De Luca}, Leonardo and Filippo Ottani and {De Luca}, Giuseppe and Federico Piscione and Nadia Moffa and {De Servi}, Stefano",
note = "{\circledC} 2018 American Heart Association, Inc.",
year = "2018",
month = "6",
day = "5",
doi = "10.1161/CIRCULATIONAHA.117.032180",
language = "English",
volume = "137",
pages = "2435--2445",
journal = "Circulation",
issn = "0009-7322",
publisher = "Lippincott Williams and Wilkins",
number = "23",

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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 - Elderly ACS-2 Investigators

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 - Petronio, A Sonia

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

N1 - © 2018 American Heart Association, Inc.

PY - 2018/6/5

Y1 - 2018/6/5

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.CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01777503.

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.CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01777503.

U2 - 10.1161/CIRCULATIONAHA.117.032180

DO - 10.1161/CIRCULATIONAHA.117.032180

M3 - Article

C2 - 29459361

VL - 137

SP - 2435

EP - 2445

JO - Circulation

JF - Circulation

SN - 0009-7322

IS - 23

ER -