Arnob Haque     

Background: Myocardial infarction (MI) is a leading cause of morbidity and mortality worldwide, with over 800,000 cases occurring annually in the United States [1]. Despite advances in percutaneous coronary intervention (PCI), MI remains a significant burden due to the risk of ischemia/reperfusion injury, microvascular damage, and cardiac remodeling [2][3]. The “no-reflow” phenomenon, characterized by poor perfusion of terminating arteries, contributes to adverse cardiac remodeling, leading to reduced ejection fraction and increased risk of heart failure [4][5]. Platelets play a crucial role in cardiac remodeling, and the inhibition of P2Y₁₂ receptors, primarily involved in platelet aggregation, has been shown to have cardioprotective effects [6]. However, the current standard of care, dual antiplatelet therapy with aspirin and clopidogrel, has limitations due to clopidogrel’s variable efficacy and potency [7]. This knowledge gap highlights the need for a comprehensive review of the literature on the role of P2Y₁₂ inhibitors in mitigating cardiac remodeling after MI.

Research Objectives: The purpose of this study is to review the current evidence on the efficacy of P2Y₁₂ inhibitors, particularly prasugrel and ticagrelor, in reducing cardiac injury and mitigating adverse remodeling after MI. The aim is to investigate the hypothesis that potent P2Y₁₂ inhibitors can improve cardiac outcomes by reducing infarct size and mitigating microvascular obstruction.

Methods: A literature search was conducted using PubMed with search terms including “P2Y12 inhibitors,” “myocardial infarction,” “cardiac remodeling,” “prasugrel,” and “ticagrelor.” Relevant studies published in English between 2019 and 2024 were included.

Results: The review found that prasugrel and ticagrelor are more potent P2Y₁₂ inhibitors than clopidogrel [7][8]. Prasugrel was shown to limit infarct size and improve cardiac enzymes, while ticagrelor demonstrated a significant reduction in cardiac remodeling in patients with TIMI grade 0 [8]. Ticagrelor’s benefits were concentrated in the chronic stages of cardiac remodeling, with a 44% reduction in risk of cardiac remodeling compared to clopidogrel [8]. However, the predictive power of platelet reactivity as an independent predictor of cardiac remodeling was determined to be limited [8].

Conclusion: This review highlights the importance of potent P2Y₁₂ inhibitors in mitigating cardiac remodeling after MI. The findings suggest that ticagrelor, in particular, may offer a more effective strategy for reducing cardiac injury and adverse remodeling [8]. The implications are significant as they may inform optimal use of P2Y₁₂ inhibitors in post-MI care. Future investigations should determine the long-term effects of P2Y₁₂ inhibitors on patient outcomes and explore the mechanisms underlying their cardioprotective effects.

Works Cited:

1. CDC. Heart Disease Facts | cdc.gov. Centers for Disease Control and Prevention. Published May 15, 2023. Accessed April 6, 2024. https://www.cdc.gov/heartdisease/facts.htm
2. Moore A, Goerne H, Rajiah P, Tanabe Y, Saboo S, Abbara S. Acute myocardial infarct. Radiologic Clinics of North America. 2019;57(1):45-55.
3. White K, Kinarivala M, Scott I. Diagnostic features, management and prognosis of type 2 myocardial infarction compared to type 1 myocardial infarction: a systematic review and meta-analysis. BMJ Open. 2022;12(2):e055755.
4. Lindahl B, Mills NL. A new clinical classification of acute myocardial infarction. Nat Med. 2023;29(9):2200-2205.
5. Bhatt DL, Lopes RD, Harrington RA. Diagnosis and treatment of acute coronary syndromes: a review. JAMA. 2022;327(7):662-675
6. Simonato D, Borchert RJ, Labeyrie MA, et al. Glycoprotein IIb/IIIa inhibitors for the neurointerventionalist. Interv Neuroradiol. 2022;28(1):84-91.
7. Kitano D, Takayama T, Fukamachi D, et al. Impact of low-dose prasugrel on platelet reactivity and cardiac dysfunction in acute coronary syndrome patients requiring primary drug-eluting stent implantation: A randomized comparative study. Catheter Cardiovasc Interv. 2020;95(1):E8-E16. doi:10.1002/ccd.28277
8. Park Y, Koh JS, Lee JH, et al. Effect of Ticagrelor on Left Ventricular Remodeling in Patients With ST-Segment Elevation Myocardial Infarction (HEALING-AMI). JACC Cardiovasc Interv. 2020;13(19):2220-2234. doi:10.1016/j.jcin.2020.08.007