Infarct Size Following Treatment With Second‐ Versus Third‐Generation P2Y ₁₂ Antagonists in Patients With Multivessel Coronary Disease at ST‐Segment Elevation Myocardial Infarction in the CvLPRIT Study

Abstract

BackgroundThird‐generation P2Y12 antagonists (prasugrel and ticagrelor) are recommended in guidelines on ST‐segment elevation myocardial infarction. Mechanisms translating their more potent antiplatelet activity into improved clinical outcomes versus the second‐generation P2Y12 antagonist clopidogrel are unclear. The aim of this post hoc analysis of the Complete Versus Lesion‐Only PRImary PCI Trial‐CMR (CvLPRIT‐CMR) substudy was to assess whether prasugrel and ticagrelor were associated with reduced infarct size compared with clopidogrel in patients undergoing primary percutaneous coronary intervention.Methods and ResultsCvLPRIT‐CMR was a multicenter, prospective, randomized, open‐label, blinded end point trial in 203 ST‐segment elevation myocardial infarction patients with multivessel disease undergoing primary percutaneous coronary intervention with either infarct‐related artery–only or complete revascularization. P2Y12 inhibitors were administered according to local guidelines. The primary end point of infarct size on cardiovascular magnetic resonance was not significantly different between the randomized groups. P2Y12 antagonist administration was not randomized. Patients receiving clopidogrel (n=70) compared with those treated with either prasugrel or ticagrelor (n=133) were older (67.8±12 versus 61.5±10 years, P<0.001), more frequently had hypertension (49% versus 29%, P=0.007), and tended to have longer symptom‐to‐revascularization time (234 versus 177 minutes, P=0.05). Infarct size (median 16.1% [quartiles 1–3, 10.5–27.7%] versus 12.1% [quartiles 1–3, 4.8–20.7%] of left ventricular mass, P=0.013) and microvascular obstruction incidence (65.7% versus 48.9%, P=0.022) were significantly greater in patients receiving clopidogrel. Infarct size remained significantly different after adjustment for important covariates using both generalized linear models (P=0.048) and propensity score matching (P=0.025).ConclusionsIn this analysis of CvLPRIT‐CMR, third‐generation P2Y12 antagonists were associated with smaller infarct size and lower microvascular obstruction incidence versus the second‐generation P2Y12 antagonist clopidogrel for ST‐segment elevation myocardial infarction.Clinical Trial Registration URL: http://www.isrctn.com/ISRCTN70913605.

Time to Give Up on Cardioprotection?

“…A particular problem for the translation of cardioprotection by conditioning strategies may be the increasing use of novel and more potent P2Y 12 antagonists which-independently from their platelet inhibitory action-recruit signal transduction steps of conditioning 223 and reduce infarct size per se. [224][225][226] In conclusion, a multitude of potential reasons (species differences, reductionist models, aging, comorbidities, and comedications) and their combination easily explain why data from experimental animals cannot be readily translated to use in patients having an AMI or undergoing a cardiovascular intervention. Hospital stay ↓n.s.…”

Mechanical and Pharmacological Revascularization Strategies for Prevention of Microvascular Dysfunction in ST-Segment Elevation Myocardial Infarction: Analysis from Index of Microcirculatory Resistance Registry Data

“…When compared with potent inhibition of platelet function, ticagrelor and prasugrel inhibit approximately 94% and 90%, respectively, in those with aspirin, whereas clopidogrel typically achieves a maximum of only 50% platelet inhibition in combination with aspirin in ACS. Ticagrelor and prasugrel are faster than clopidogrel in reaching its peak concentration (peak effect after loading dose at 2 hours for ticagrelor, 4 hours for prasugrel, and 6 hours for clopidogrel) and has been shown to increase adenosine plasma concentration associated with an inhibition of adenosine uptake of red blood cells, stimulating vasodilatation [ 35 – 37 ]. In our study, microvascular injury was reduced more in the third-generation P2Y12 inhibitors group.…”

Multimarker approach for the prediction of microvascular obstruction after acute ST-segment elevation myocardial infarction: a prospective, observational study

“…Besides its ability for accurate quantification of ventricular function, morphology and infarct size, CMR imaging has emerged as the most reliable imaging modality to detect microvascular injury and is therefore more and more used to define surrogate endpoints in clinical trials [5, 26, 27]. There is strong evidence that presence of MVO derived from late gadolinium-enhanced images is the best CMR prognosticator regarding clinical outcome after acute reperfused STEMI [3, 7].…”