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Timing of P2Y12 Inhibitors in STEMI Patients Undergoing PPCI
Quick Takes
- Early administration of P2Y12 inhibitors was associated with a significantly lower risk of ischemic events and mortality, without safety concerns.
- The risk reduction for MACE varied across the cumulative duration of P2Y12 inhibitor exposure before primary PCI, in that the potential benefits of pretreatment only became evident after ≥80 minutes following the loading dose administration.
- Additional prospective studies are needed to validate the study findings and determine the choice, and optimal timing of P2Y12 inhibitor administration for patients with STEMI undergoing primary PCI.
Study Questions:
What is the safety and effectiveness of P2Y12 inhibitor pretreatment in patients transferred for primary percutaneous coronary intervention (PPCI) within a regional ST-segment elevation myocardial infarction (STEMI) network?
Methods:
The investigators conducted a subanalysis from the CREA-ARIAM Andalucía registry (Safety and Efficacy of Antiplatelet Switching in Acute Coronary Syndrome), a prospective, multicenter, investigator-initiated branch of the main ARIAM-Andalucía registry (Analysis of Delay in Acute Myocardial Infarction in Andalucía). For the current analysis, STEMI patients included in the CREA-ARIAM registry at six academic hospitals between March 2015 and April 2019 were prospectively screened for eligibility if they were scheduled to undergo PPCI within 24 hours of symptom onset. Pretreatment was defined as P2Y12 inhibitor administration before coronary angiography. Endpoints were major adverse cardiac events (MACE), major bleeding, and net adverse clinical events, a composite of MACE or major bleeding, within 30 days of index admission. Association of P2Y12 inhibitor pretreatment with outcomes was modeled using doubly robust weighted estimators based on propensity score analysis.
Results:
Of 1,624 patients included, 1,033 received P2Y12 inhibitors before angiography and 591 in the catheterization laboratory (cath lab). The non–pretreated cohort more often had a history of coronary artery disease and were more likely to receive antiplatelet therapy before the index admission. After adjustment for confounding and dependent censoring, pretreatment with P2Y12 inhibitors predicted lower risk of MACE (adjusted hazard ratio [aHR], 0.53; 95% confidence interval [CI], 0.37-0.76), without increasing bleeding risk (aHR, 0.62; 95% CI, 0.36-1.05), resulting in superior net clinical benefit (aHR, 0.47; 95% CI, 0.26-0.86) compared with in-cath lab administration of P2Y12 inhibitors. There was a significant treatment-by-time interaction for MACE risk, whereby the observed benefits of pretreatment only became apparent when time between P2Y12 inhibitor administration and PCI was longer than 80 minutes.
Conclusions:
The authors report that in contemporary patients with STEMI transferred for PPCI, pretreatment with P2Y12 inhibitors was associated with a significant time-dependent reduction of 30-day MACE without increasing bleeding risk.
Perspective:
This registry study of patients with STEMI transferred for PPCI reports that early administration of P2Y12 inhibitors was associated with a significantly lower risk of ischemic events and mortality, without bleeding risk, thereby resulting in a superior net clinical benefit compared with a delayed P2Y12 inhibitor loading strategy. Furthermore, the risk reduction for MACE varied across the cumulative duration of P2Y12 inhibitor exposure before PPCI, in that the potential benefits of pretreatment only became evident after ≥80 minutes following the loading dose administration. Given several limitations of the current analysis and conflicting data on the benefits of pretreatment with a P2Y12 inhibitor before the anatomy is known, additional prospective studies are needed to validate these study findings and determine the choice and optimal timing of P2Y12 inhibitor administration for patients with STEMI undergoing primary PCI.
Clinical Topics: Invasive Cardiovascular Angiography and Intervention, Stable Ischemic Heart Disease, Vascular Medicine, Interventions and Vascular Medicine, Chronic Angina
Keywords: Percutaneous Coronary Intervention, Receptors, Purinergic P2Y12, ST Elevation Myocardial Infarction
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