Original Investigation
Effect of Prasugrel Pre-Treatment Strategy in Patients Undergoing Percutaneous Coronary Intervention for NSTEMI: The ACCOAST-PCI Study

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Abstract

Background

After percutaneous coronary intervention (PCI) for non–ST-segment elevation myocardial infarction (NSTEMI), treatment with a P2Y12 antagonist with aspirin is recommended for 1 year.

Objectives

The oral P2Y12 antagonists ticagrelor and prasugrel have higher recommendations than clopidogrel, but it is unknown if administration before the start of PCI is beneficial.

Methods

In the randomized, double-blind ACCOAST (A Comparison of prasugrel at the time of percutaneous Coronary intervention Or as pre-treatment At the time of diagnosis in patients with non–ST-segment elevation myocardial infarction) trial, 4,033 patients were diagnosed with NSTEMI and 68.7% underwent PCI; 1,394 received pre-treatment with prasugrel (30-mg loading dose), and 1,376 received placebo. At the time of PCI, patients who received pre-treatment with prasugrel received an additional 30-mg dose of prasugrel, and those who received placebo received a 60-mg loading dose of prasugrel. Primary efficacy was a composite of cardiovascular death, myocardial infarction, stroke, urgent revascularization, or glycoprotein IIb/IIIa bailout through 7 days from randomization. Investigators captured the presence of thrombus on initial angiography and during PCI.

Results

The incidence of the primary endpoint through 7 days from randomization in the pre-treatment group versus the no pre-treatment group was 13.1% versus 13.1% (p = 0.93). Pre-treatment with prasugrel was not associated with decreases in any ischemic event, including total mortality. Patients with thrombus on angiography had a 3-fold higher incidence of the primary endpoint than patients without thrombus. There was no impact of pre-treatment with prasugrel on the presence of thrombus before PCI or on occurrence of stent thrombosis after PCI. There was a 3-fold increase in all non–coronary artery bypass graft Thrombolysis In Myocardial Infarction (TIMI) major bleeding and a 6-fold increase in non–coronary artery bypass graft life-threatening bleeding with pre-treatment with prasugrel; the same trends persisted in patients who had radial or femoral access even with use of a closure device.

Conclusions

These findings support deferring treatment with prasugrel until a decision is made about revascularization in patients with NSTEMI undergoing angiography within 48 h of admission. (A Comparison of prasugrel at the time of percutaneous Coronary intervention Or as pre-treatment At the time of diagnosis in patients with non—ST-segment elevation myocardial infarction [ACCOAST]; NCT01015287)

Key Words

acute coronary syndromes(s)
percutaneous coronary intervention
prasugrel

Abbreviations and Acronyms

CABG
coronary artery bypass graft
CI
confidence interval
GP
glycoprotein
HR
hazard ratio
NSTE-ACS
non–ST-segment elevation acute coronary syndrome
NSTEMI
non–ST-segment elevation myocardial infarction
PCI
percutaneous coronary intervention
TIMI
Thrombolysis In Myocardial Infarction

Cited by (0)

The trial was sponsored by Daiichi Sankyo Co., Ltd., and Eli Lilly and Company, and the coordinating center was the ACTION Study Group at the Institute of Cardiology of Pitié-Salpêtrière Hospital. Data were collected, managed, and analyzed by a clinical research organization contracted by the sponsors according to the protocol and a pre-defined statistical analysis plan.

Dr. Montalescot has received consulting fees from Bayer, Boehringer Ingelheim, CFR, Europa, GLG, Iroko Cardio International, Lead-Up, LLC, Luminex, McKinsey, Remedica, Servier, TIMI Group, WebMD, and Wolters; consulting fees and grant support from Bristol-Myers Squibb, AstraZeneca, Biotronik, Eli Lilly, The Medicines Company, Medtronic, Menarini, Sanofi, Pfizer, and Accumetrics; and grant support from Abbott Vascular, Daiichi Sankyo, Nanospheres, and Stentys. Dr. Collet has received research grants from Bristol-Myers Squibb, Sanofi, Eli Lilly, Guerbet Medical, Medtronic, Boston Scientific, Cordis, Stago, Centocor, Fondation de France, INSERM, Fédération Française de Cardiologie and Société Française de Cardiologie; consulting fees from Sanofi, Eli Lilly, and Bristol-Myers Squibb; and lecture fees from Bristol-Myers Squibb, Sanofi, and Eli Lilly.

Dr. Bolognese has received fees for board membership from Daiichi Sankyo and Eli Lilly; consulting fees from Daiichi Sankyo; and lecture fees from Daiichi Sankyo, Eli Lilly, Menarini, Abbott, AstraZeneca, and Iroko Cardio International. Dr. ten Berg has received fees for board membership from AstraZeneca; consulting fees from AstraZeneca, Eli Lilly, and Merck; and lecture fees from AstraZeneca and Eli Lilly. Dr. Dudek has received consulting and lecture fees from Abbott, Adamed, Adyton Medical Polska, Abiomed Europe, AstraZeneca, Biotronik, Balton, Bayer, Braun, BioMatrix, Boston Scientific, Boehringer Ingelheim, Bracco, Bristol-Myers Squibb, Comesa Polska, Cordis, Cook, Covidien Polska, DRG MedTek, Eli Lilly, EuroCor, Hammermed, GE Healthcare, GlaxoSmithKline, Inspire-MD, Iroko Cardio International, Medianet, Medtronic, The Medicines Company, Meril Life Sciences, Merck Sharp & Dohme, Orbus-Neich, Pfizer, Possis, ProCardia Medical, Promed, REVA Medical, Sanofi, Siemens, Solvay, Stentys, St. Jude Medical, Terumo, Tyco, and Volcano. Dr. Hamm has received payment for board membership from AstraZeneca, Medtronic, and Boehringer Ingelheim; consulting and lecture fees from Medtronic, Boehringer Ingelheim, Eli Lilly, The Medicines Company, Abbott Vascular, Bayer, Sanofi, Boston Scientific, Correvio, Roche Diagnostics, Pfizer, Cordis, Daiichi Sankyo, and GlaxoSmithKline; and lecture fees from AstraZeneca and Merck. Dr. Widimsky has received consulting and lecture fees from Eli Lilly and Daiichi Sankyo. Dr. Tanguay has received consulting fees from Eli Lilly, AstraZeneca, Abbott Vascular, Roche, and GlaxoSmithKline; lecture fees from Sanofi, Eli Lilly, AstraZeneca, Abbott Vascular, Pfizer, and Bristol-Myers Squibb; and grant support from Eli Lilly, AstraZeneca, Roche, Hexacath, Ikaria, Abbott Vascular, GlaxoSmithKline, Roche, and Sanofi. Dr. Goldstein has received fees for board membership from Boehringer Ingelheim, The Medicines Company, and Daiichi-Sankyo; consulting fees from Boehringer Ingelheim, Bayer, Sanofi, and AstraZeneca; lecture fees from Boehringer Ingelheim, The Medicines Company, Daiichi-Sankyo, Bayer, Sanofi, and AstraZeneca; payment for the development of educational presentations from Boehringer Ingleheim and AstraZeneca; and travel support from Boehringer Ingelheim, Daiichi-Sankyo, and Sanofi. Dr. Brown, Ms. Miller, and Dr. LeNarz are employees of and hold stock in Eli Lilly. Dr. Vicaut has received fees for board membership from CERC; consulting fees from Eli Lilly, Novartis, Pfizer, Sanofi, LFB, Abbott, Fresenius, Medtronic, and Hexacath; lecture fees from Novartis; and grant support from Sanofi, AstraZeneca, and Boehringer Ingelheim. Dr. Ecollan has reported that he has no relationships relevant to the contents of this paper to disclose.

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