The effect of P2Y12 inhibitor pretreatment vs. no pretreatment on ischemic outcomes among patients with NSTE-ACS: an updated meta-analysis and meta-regression pooling 106,405 patients from 12 studies
Authors: Borovac J A , D'Amario D , Schwarz K , Bozic J , Glavas D ,   Cardiometabolic Research Group
Published: October 2021

Abstract

Background
Recent European Society of Cardiology guidelines for the management of non-ST elevation acute coronary syndromes (NSTE-ACS) do not recommend routine pretreatment with P2Y12 inhibitors in patients in whom coronary anatomy is not known and an early invasive management is planned.

Purpose
To determine if updated pooled data is in line with the latest recommendations, we investigated the impact of P2Y12 pretreatment on short-term ischemic outcomes among patients with NSTE-ACS.

Methods
MEDLINE and EMBASE databases were systematically searched to find interventional or observational studies that investigated the use of P2Y12 inhibitors as a pretreatment vs. no pretreatment in patients presenting with NSTE-ACS. Studies that reported short-term outcomes during hospitalization or up to 30 days were included. The primary outcome was a composite of ischemic events consisting of death, myocardial infarction, stroke, and unplanned revascularization. Random-effects meta-analysis was performed with prespecified subgroup analyses concerning more potent P2Y12 inhibitor use and drug-eluting stent (DES) uptake &gt;50%. For the primary analysis, the odds ratio (OR) with 95% confidence intervals (95% CI) were reported. Heterogeneity across studies was inspected by I2 statistic. Meta-regression assessed the potential interaction of variables including percutaneous coronary intervention (PCI) receipt, NSTE-ACS subtype, DES uptake &gt;50%, and potent P2Y12 inhibitor use with the primary outcome.

Results
Twelve studies were included (6 RCTs, 5 registry-based studies, and 1 prespecified analysis of an RCT) providing a total of 106,405 patients with pooled 4,076 ischemic events (2,775 in the pretreatment and 1,301 in a no-pretreatment group). Most of the studies were older than 10 years and used clopidogrel as a pretreatment while the average rate of PCI receipt was 79%. Low-to-moderate heterogeneity was detected among studies. Although pretreatment with P2Y12 inhibitors reduced the likelihood of short-term ischemic events across all studies included, in contemporary NSTE-ACS cohorts with high penetration of DES platforms and agents more potent than clopidogrel, this effect was not sustained (OR 0.905, 95% CI 0.741–1.107 – Figure 1 and OR 0.846, 95% CI 0.645–1.109 – Figure 2). Of all variables, the use of potent P2Y12 inhibitors was independently associated with a reduction of the primary outcome in meta-regression analysis (coefficient −0.879, 95% CI −1.316 to −0.442, P&lt;0.0001).

Conclusions
Our pooled 2021 data reinforces the current evidence as early P2Y12 pretreatment was not associated with significant short-term ischemic benefits in contemporary NSTE-ACS cohorts while the use of potent P2Y12 agents independently interacted with the primary outcome. Finally, factors such as receipt of early PCI, use of modern DES platforms, and more potent antiplatelet inhibition administered periprocedurally will likely obviate the need for pretreatment in this population.

Funding Acknowledgement
Type of funding sources: None. Figure 1. Ischemic events and DES useFigure 2. Ischemic events and P2Y12 type