Pre-angiography treatment with oral P2Y12 inhibitors in non-ST elevation acute coronary syndromes (NSTEACS) was associated with no benefit in cardiac outcomes, but it was associated with an increased risk of bleeding, a systematic review and meta-analysis showed.
Pretreatment was not associated with a reduction in 30-day major adverse cardiac events (MACE; odds ratio [OR] 0.95, 95% CI 0.78-1.15), 30-day myocardial infarction (OR 0.90, 95% CI 0.72-1.12), or 30-day cardiovascular death (OR 0.79, 95% CI 0.49-1.27), reported Luke Dawson, MBBS, MPH, of the Alfred Hospital in Melbourne, Australia, and co-authors. However, it was associated with increased risk of 30-day major bleeding (OR 1.51, 95% CI 1.16-1.97), they reported in JAMA Network Open. The number needed to harm for one major bleeding event was 63 patients.
“Routine pretreatment with oral P2Y12 inhibitors in patients with NSTEACS receiving an early invasive strategy is not supported by this study,” Dawson and colleagues wrote.
“It is now time to change practice as elegantly demonstrated by the systematic review and meta-analysis of Dawson et al who reviewed seven trials, published during the last 20 years, that evaluated pretreatment with oral P2Y12 inhibitors in patients with NSTEACS,” observed Michel Zeitouni, MD, and Jean-Philippe Collet, MD, PhD, both of Sorbonne Université in Paris, France, in an accompanying editorial.
“Their key message is that the strategy of systematic pretreatment with a P2Y12 inhibitor in patients with NSTE-ACS does not confer any ischemic benefit but may be associated with harm,” Zeitouni and Collet wrote. “The association with harm was especially driven by the findings of the Pretreatment at the Time of Diagnosis in Patients with Non-ST Elevation Myocardial Infarction (ACCOAST) trial and the Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment (ISAR-REACT 5) trial and was consistent irrespectively of the type of P2Y12 inhibitor and vascular access used.”
“If interventionalists are concerned about the risk of peri-intervention MI, the use of intravenous P2Y12 inhibitor is an additional option demonstrated to be effective in naïve patients,” they added.
Dawson and colleagues conducted their literature search in March 2021, including randomized clinical trials of patients with an acute coronary syndrome who were randomized to oral P2Y12 inhibitor pretreatment (prior to angiography) or no pretreatment (following angiography, i.e., once coronary anatomy was known). Data were stratified by P2Y12 inhibitor type, revascularization strategy, and access site. P2Y12 inhibitors were ticagrelor, prasugrel, and clopidogrel.
The analysis drew on seven trials with 13,226 patients overall, with 6,603 in the pretreatment and 6,623 in the no pretreatment groups. Mean age was 63.5 and 27.2% of participants were women. MACE at 30 days was the primary endpoint, with a primary safety end point of 30-day major bleeding.
Indication for P2Y12 inhibitors was non-ST elevation myocardial infarction in 7,430 patients (61.7%), while radial access angiography/percutaneous coronary intervention (PCI) was used in 4,295 (32.6%), and 10,945 (82.8%) underwent PCI.
“Findings were generally consistent when stratified by oral P2Y12 inhibitor type, revascularization strategy, and arterial access site, with the exception of reduced MACEs among the group receiving clopidogrel treatment (reliant on the PCI CURE trial) and no significant difference in bleeding risk among patients undergoing surgery with radial access,” the researchers wrote.
In acute coronary syndromes, early inhibition of thromboxane A2, adenosine diphosphate, and thrombin limits coronary plaque thrombosis and helps avoid peri-interventional myocardial infarction while waiting for angiography. While intravenous agents take effect very quickly, the action of oral P2Y12 inhibitors takes longer from time of dosing. Pre-treatment involves giving all suspected of having an acute coronary syndrome an oral P2Y12 inhibitor and aspirin, often pre-hospital, before angiography reveals coronary anatomy. This increases bleeding risk just before arterial puncture and the procedure itself.
A 2021 review of acute coronary syndrome management noted that while U.S. and European guidelines recommended timely P2Y12 inhibitor initiation in ST elevation myocardial infarction (STEMI) despite questions of efficacy, a study of pre-hospital ticagrelor did not improve pre-hospital, pre-intervention coronary reperfusion though it appeared safe. “The timing of P2Y12 inhibitor initiation in NSTEMI similarly has been a historic area of controversy,” the review authors wrote.
The 2020 DUBIUS clinical trial evaluated patients randomized to pre-treatment with ticagrelor before angiography or no pre-treatment. The study reported a low incidence of ischemic and bleeding events leading to premature termination of the trial with results suggesting “unlikelihood of enhanced efficacy of one strategy over the other.”
“Pretreatment with oral P2Y12 inhibitors in patients with NSTEACS has been extensively discussed over the last two decades,” Dawson and co-authors noted.
“However, randomized data do not support this approach,” they continued. “Until last year, European guidelines have recommended pretreatment with oral P2Y12 inhibitors in patients with NSTEACS with the caveat of limiting this advice to ticagrelor and clopidogrel, given the results of the ACCOAST trial, which showed no benefit with prasugrel pretreatment. U.S. guidelines have remained more cautious but are yet to recommend against the use of routine pretreatment.”
The researchers acknowledged that the number needed to harm estimated in this study (i.e., 63 patients) may overestimate the bleeding risk of pretreatment among contemporary cohorts undergoing radial access. Other limitations include a small sample size for some subgroups, the use of different bleeding definitions, and the use of different P2Y12 inhibitors, and variations in time between pretreatment and angiography.
-
Pre-angiography treatment with oral P2Y12 inhibitors in non-ST elevation acute coronary syndromes (NSTEACS) was associated with no benefit in cardiac outcomes, but it was associated with harm of increased bleeding, a systematic review and meta-analysis showed.
-
Routine pretreatment with oral P2Y12 inhibitors in patients with NSTEACS receiving an early invasive strategy was not supported by this analysis, the researchers concluded.
Paul Smyth, MD, Contributing Writer, BreakingMED™
Researchers were supported by the National Health and Medical Research Council and the National Heart Foundation.
Dawson reported no disclosures.
Collet reported serving as chairman of the European Society of Cardiology 2020 NSTE-ACS guidelines and receiving grants from Medtronic and Boston Scientific and personal fees from AstraZeneca and BMS-Pfizer Alliance outside the submitted work.
Zeitouni reported no disclosures.
Cat ID: 308
Topic ID: 74,308,730,308,5,914,192,925
