Effect of Prasugrel Pre-Treatment Strategy in Patients Undergoing Percutaneous Coronary Intervention for NSTEMI
Key result
Prasugrel pre-treatment in NSTEMI shows no ischemic benefit but increases TIMI major bleeding ~3-fold.
- P=0.93
- n=4,033
Why the study?
Although oral P2Y12 antagonists such as ticagrelor and prasugrel have higher recommendations than clopidogrel after PCI for NSTEMI, whether administration before PCI is beneficial remains unknown.
Key Points
- To determine whether pre-treatment with the oral P2Y12 antagonist prasugrel prior to percutaneous coronary intervention reduces ischemic outcomes without excessive bleeding in patients with non-ST-segment elevation myocardial infarction.
- In the randomized, double-blind ACCOAST trial (NCT01015287), 4,033 patients were diagnosed with NSTEMI, of whom 68.7% underwent PCI.
- Patients were randomized to receive either pre-treatment with a 30-mg loading dose of prasugrel (N=1,394) followed by 30 mg at PCI, or placebo pre-treatment (N=1,376) followed by a standard 60-mg loading dose at PCI.
- The primary efficacy endpoint was a composite of cardiovascular death, myocardial infarction, stroke, urgent revascularization, or glycoprotein IIb/IIIa bailout through 7 days from randomization.
- The primary endpoint occurred in 13.1% of patients in the pre-treatment group versus 13.1% in the no pre-treatment group (p = 0.93), demonstrating no decrease in any ischemic event or total mortality.
- Pre-treatment had no effect on initial angiographic thrombus presence or post-PCI stent thrombosis, although patients presenting with thrombus had a 3-fold higher rate of the primary endpoint.
- Prasugrel pre-treatment resulted in a 3-fold increase in non-CABG TIMI major bleeding and a 6-fold increase in non-CABG life-threatening bleeding, irrespective of radial or femoral access.
Study Design
Type
RCT (n=4,033)
Blinding
double-blind
Randomization
randomized
PICO
P
Population
4,033 patients diagnosed with NSTEMI, followed for 7 days from randomization.
I
Intervention / Comparator
Prasugrel pre-treatment vs Placebo before PCI, then 60-mg loading dose of prasugrel at PCI (30-mg loading dose before PCI, then additional 30-mg dose at PCI)
O
Primary Outcome
Composite of cardiovascular death, myocardial infarction, stroke, urgent revascularization, or glycoprotein IIb/IIIa bailout through 7 days from randomization, p=0.93
Main Result
Absolute Event Rate: 13.1% vs 13.1%
p-value: p=0.93
Key expert perspectives
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“With the rapid onset of action of the oral and intravenous P2Y12 inhibitors and the modern era of short delays between hospital admission and catheterization, the risk of an ischemic complication before catheterization is extremely low, suggesting that there is no longer a need for pre-treatment in NSTE-ACS patients to prevent ischemic complications while waiting for catheterization. Moreover, there is also no benefit of pre-treatment on peri-PCI complications. Together, our findings suggest use of prasugrel should be considered only after the coronary anatomy has been defined.”
PJPeter JuniDirector, Clinical Trials Unit, University of Bern
“In NSTE-ACS patients managed invasively within 48 hours of admission, pre-treatment with prasugrel did not reduce major ischaemic events through 30 days, but increased major bleeding complications.”
ABAndreas BaumbachInterventional cardiologist, University of Bristol
“The ACCOAST trial is a wonderful trial that has tried to answer the clinically relevant question of whether pre-treatment with prasugrel would be beneficial to patients. The study was conducted within a practice environment that was situated with rapid access to a cath lab, showed that there is no benefit for pre-treatment with this half dose of prasugrel. It also showed more bleeding events in patients who received this dose. There are a number of very interesting questions about this trial, the main being that we are not sure whether we can extrapolate these results to pre-treatment with other drugs that have been shown to be beneficial in other trials.”
Implication
Randomized double-blind trial reveals no ischemic benefit and increased bleeding with prasugrel pre-treatment in NSTEMI undergoing PCI, indicating prasugrel should be deferred until angiography.
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).
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Cite This Study
Montalescot et al. (2014) conducted an RCT in NSTEMI (n=4,033). Prasugrel pre-treatment vs. Placebo before PCI, then 60-mg loading dose of prasugrel at PCI was evaluated on Composite of cardiovascular death, myocardial infarction, stroke, urgent revascularization, or glycoprotein IIb/IIIa bailout through 7 days from randomization (p=0.93). Prasugrel pre-treatment in NSTEMI patients did not reduce the primary composite ischemic endpoint compared to no pre-treatment (13.1% vs 13.1%, p=0.93) but increased TIMI major bleeding 3-fold.