Assessment of Pretreatment With Oral P2Y12 Inhibitors and Cardiovascular and Bleeding Outcomes in Patients With Non-ST Elevation Acute Coronary Syndromes

Luke P Dawson,Jason Bloom,Misha Dagan,Jeffrey Lefkovits,James Shaw,Dion Stub,David Chen,Stephen J Duffy,Andrew Taylor

doi:10.1001/jamanetworkopen.2021.34322

Abstract

The practice of pretreatment with oral P2Y12 inhibitors in non-ST elevation acute coronary syndromes (NSTEACS) remains common; however, its association with improved cardiovascular outcomes is unclear. To assess the association between oral P2Y12 inhibitor pretreatment and cardiovascular and bleeding outcomes in patients with NSTEACS. On March 20, 2021, PubMed, MEDLINE, Embase, Scopus, Web of Science, Science Direct, clinicaltrials.gov, and the Cochrane Central Register for Controlled Trials were searched from database inception. Randomized clinical trials of patients with NSTEACS randomized to either oral P2Y12 inhibitor pretreatment (defined as prior to angiography) or no pretreatment (defined as following angiography, once coronary anatomy was known) among patients undergoing an invasive strategy. This study followed Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Data on publication year, sample size, clinical characteristics, revascularization strategy, P2Y12 inhibitor type and dosage, time from pretreatment to angiography, and end point data were independently extracted by 2 authors. A random-effects model was used, including stratification by (1) P2Y12 inhibitor type, (2) revascularization strategy, and (3) access site. The primary end point was 30-day major adverse cardiac events (MACEs). Secondary end points were 30-day myocardial infarction (MI) and cardiovascular death. The primary safety end point was 30-day major bleeding (defined according to individual studies). A total of 7 trials randomizing 13 226 patients to either pretreatment (6603 patients) or no pretreatment (6623 patients) were included. The mean age of patients was 64 years and 3598 (27.2%) were female individuals. Indication for P2Y12 inhibitors was non-ST elevation myocardial infarction in 7430 patients (61.7%), radial access was used in 4295 (32.6%), and 10 945 (82.8%) underwent percutaneous coronary intervention. Pretreatment was not associated with a reduction in 30-day MACE (odds ratio [OR], 0.95; 95% CI, 0.78-1.15; I2 = 28%), 30-day MI (OR, 0.90; 95% CI, 0.72-1.12; I2 = 19%), or 30-day cardiovascular death (OR, 0.79; 95% CI, 0.49-1.27; I2 = 0%). The risk of 30-day major bleeding was increased among patients who underwent pretreatment (OR, 1.51; 95% CI, 1.16-1.97; I2 = 41%). The number needed to harm to bring about 1 major bleeding event with oral P2Y12 inhibitor pretreatment was 63 patients. In this study, pretreatment with oral P2Y12 inhibitors among patients with NSTEACS prior to angiography, compared with treatment once coronary anatomy is known, was associated with increased bleeding risk and no difference in cardiovascular outcomes. Routine pretreatment with oral P2Y12 inhibitors in patients with NSTEACS receiving an early invasive strategy is not supported by this study.

Highlights

The timing of oral P2Y12 inhibitor administration in patients with non-ST elevation acute coronary syndromes (NSTEACS) has been a matter of substantial debate over the last 2 decades.[1,2,3,4] Pretreatment, defined as oral P2Y12 inhibitor administration prior to angiography and usually at the time of diagnosis, has been commonly used with the rationale that there may be greater platelet inhibition at time of percutaneous coronary intervention (PCI); there may be reduced ischemic events while awaiting angiography; and more potent antiplatelet agents, such as glycoprotein IIb/IIIa inhibitors, may be avoided.[4]
Pretreatment was not associated with a reduction in 30-day major adverse cardiac events (MACEs), 30-day myocardial infarction (MI) (OR, 0.90; 95% CI, 0.72-1.12; I2 = 19%), or 30-day cardiovascular death (OR, 0.79; 95% CI, 0.49-1.27; I2 = 0%)
A total of 13 226 patients were included in the analysis, with 6603 patients randomly assigned to oral P2Y12 inhibitor pretreatment and 6623 patients randomly assigned to no pretreatment

Summary

Introduction

The timing of oral P2Y12 inhibitor administration in patients with non-ST elevation acute coronary syndromes (NSTEACS) has been a matter of substantial debate over the last 2 decades.[1,2,3,4] Pretreatment, defined as oral P2Y12 inhibitor administration prior to angiography and usually at the time of diagnosis, has been commonly used with the rationale that there may be greater platelet inhibition at time of percutaneous coronary intervention (PCI); there may be reduced ischemic events while awaiting angiography; and more potent antiplatelet agents, such as glycoprotein IIb/IIIa inhibitors, may be avoided.[4]. Previous guidelines supporting a pretreatment strategy relied mostly on older and indirect data,[5,6] and the most recent comprehensive meta-analysis (performed in 2014), which did not support pretreatment, relied mostly on observational rather than randomized data.[1,7] Arguments against pretreatment mainly relate to increased bleeding risk among patients who require PCI, in addition to those who need coronary artery bypass grafting (in whom surgery may be delayed with increased risk of postoperative bleeding) and those who may have an alternate diagnosis (eg, aortic dissection). European guidelines recently changed to recommend against pretreatment in patients with NSTEACS based on several trials and observational studies.[8,9,10,11,12] debate still remains regarding the optimal approach,[13] and several further trials have been published that allow for a more comprehensive pooled systematic review

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