Ideal P2Y12 Inhibitor in Acute Coronary Syndrome: A Review and Current Status

Dual antiplatelet therapy (DAPT) has remained the cornerstone for management of acute coronary syndrome (ACS) over the years. Clopidogrel has been the quintessential P2Y12 receptor (platelet receptor for Adenosine 5′ diphosphate) inhibitor for the past two decades. With the demonstration of unequivocal superior efficacy of prasugrel/ticagrelor over clopidogrel, guidelines now recommend these agents in priority over clopidogrel in current management of ACS. Cangrelor has revived the interest in injectable antiplatelet therapy too. Albeit the increased efficacy of these newer agents comes at the cost of increased bleeding and this becomes more of a concern when combined with aspirin. Which P2Y12i is superior over another has been intensely debated over last few years after the ISAR-REACT 5 study with inconclusive data. Three novel antiplatelet agents are already in the pipeline for ACS with all of them succeeding in phase II studies. The search for an ideal antiplatelet remains a need of the hour for optimal reduction of ischemic events in ACS.

[1]  F. Iellamo,et al.  Post-exercise Hypotension in Patients With Coronary Artery Disease , 2021, Frontiers in Physiology.

[2]  M. Perrone,et al.  Circulating Soluble Lectin-like Oxidized Low-Density Lipoprotein Receptor-1 (sLOX-1): A Diagnostic Indicator across the Spectrum of Acute Coronary Syndrome , 2021, Journal of clinical medicine.

[3]  T. Behl,et al.  Framing Cause-Effect Relationship of Acute Coronary Syndrome in Patients with Chronic Kidney Disease , 2021, Diagnostics.

[4]  Chiara Salimei,et al.  The Effects of Reduced Physical Activity on the Lipid Profile in Patients with High Cardiovascular Risk during COVID-19 Lockdown , 2021, International journal of environmental research and public health.

[5]  H. Suryapranata,et al.  Gender differences with short-term vs 12 months dual antiplatelet therapy in patients with acute coronary syndrome treated with the COMBO dual therapy stent: 2-years follow-up results of the REDUCE trial , 2021, Journal of Thrombosis and Thrombolysis.

[6]  H. Schunkert,et al.  Efficacy and Safety of Revacept, a Novel Lesion-Directed Competitive Antagonist to Platelet Glycoprotein VI, in Patients Undergoing Elective Percutaneous Coronary Intervention for Stable Ischemic Heart Disease: The Randomized, Double-blind, Placebo-Controlled ISAR-PLASTER Phase 2 Trial. , 2021, JAMA cardiology.

[7]  S. Rhie,et al.  P2Y12 Antiplatelet Choice for Patients with Chronic Kidney Disease and Acute Coronary Syndrome: A Systematic Review and Meta-Analysis , 2021, Journal of personalized medicine.

[8]  W. Almahmeed,et al.  2020 Asian Pacific Society of Cardiology Consensus Recommendations on the Use of P2Y12 Receptor Antagonists in the Asia-Pacific Region , 2021, European cardiology.

[9]  M. Perrone,et al.  The underestimated issue of non-reproducible cardiac troponin I and T results: case series and systematic review of the literature , 2021, Clinical chemistry and laboratory medicine.

[10]  OUP accepted manuscript , 2021, European Heart Journal.

[11]  H. Schunkert,et al.  Ticagrelor or Prasugrel in Patients With Non-ST-Segment Elevation Acute Coronary Syndromes. , 2020, Journal of the American College of Cardiology.

[12]  H. Schunkert,et al.  Ticagrelor or Prasugrel in Patients With Acute Coronary Syndromes and Diabetes Mellitus. , 2020, JACC. Cardiovascular interventions.

[13]  Samin K. Sharma,et al.  Ticagrelor alone vs. ticagrelor plus aspirin following percutaneous coronary intervention in patients with non-ST-segment elevation acute coronary syndromes: TWILIGHT-ACS. , 2020, European heart journal.

[14]  Deepak L. Bhatt,et al.  2020 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation. , 2020, European heart journal.

[15]  G. Musumeci,et al.  Timing of Oral P2Y12 Inhibitor Administration in Non-ST Elevation Acute Coronary Syndrome. , 2020, Journal of the American College of Cardiology.

[16]  K. Bailey,et al.  Effect of Genotype-Guided Oral P2Y12 Inhibitor Selection vs Conventional Clopidogrel Therapy on Ischemic Outcomes After Percutaneous Coronary Intervention: The TAILOR-PCI Randomized Clinical Trial. , 2020, JAMA.

[17]  Y. Jang,et al.  Effect of Ticagrelor Monotherapy vs Ticagrelor With Aspirin on Major Bleeding and Cardiovascular Events in Patients With Acute Coronary Syndrome: The TICO Randomized Clinical Trial. , 2020, JAMA.

[18]  M. Valgimigli,et al.  Subcutaneous Selatogrel Inhibits Platelet Aggregation in Patients With Acute Myocardial Infarction. , 2020, Journal of the American College of Cardiology.

[19]  Salik Nazir,et al.  Meta-analysis of the efficacy and safety of P2Y12 inhibitor monotherapy after short course of dual-antiplatelet therapy in patients undergoing percutaneous coronary intervention. , 2020, Cardiovascular revascularization medicine : including molecular interventions.

[20]  S. Bungău,et al.  Acute Coronary Syndromes in Chronic Kidney Disease: Clinical and Therapeutic Characteristics , 2020, Medicina.

[21]  G. Dangas,et al.  Pharmacodynamics, pharmacokinetics, and safety of single-dose subcutaneous administration of selatogrel, a novel P2Y12 receptor antagonist, in patients with chronic coronary syndromes , 2019, European heart journal.

[22]  D. Gallo,et al.  P2Y12 inhibitors in acute coronary syndrome patients with renal dysfunction: an analysis from the RENAMI and BleeMACS projects. , 2019, European heart journal. Cardiovascular pharmacotherapy.

[23]  F. Romeo,et al.  Serum free light chains in patients with ST elevation myocardial infarction (STEMI): A possible correlation with left ventricle dysfunction. , 2019, International journal of cardiology.

[24]  B. Coller,et al.  Preclinical studies of RUC-4, a novel platelet αIIbβ3 antagonist, in non-human primates and with human platelets , 2019, Journal of Clinical and Translational Science.

[25]  M. Vaduganathan,et al.  Premature Ticagrelor Discontinuation in Secondary Prevention of Atherosclerotic CVD: JACC Review Topic of the Week. , 2019, Journal of the American College of Cardiology.

[26]  L. Piegas,et al.  Ticagrelor Versus Clopidogrel in Patients With STEMI Treated With Fibrinolysis: TREAT Trial. , 2019, Journal of the American College of Cardiology.

[27]  D. Angiolillo,et al.  Pre-Treatment With Oral P2Y12 Inhibitors in Acute Coronary Syndromes Without ST-Segment Elevation: The Saga Continues. , 2019, Journal of the American College of Cardiology.

[28]  S. Cook,et al.  Six months versus 12 months dual antiplatelet therapy after drug-eluting stent implantation in ST-elevation myocardial infarction (DAPT-STEMI): randomised, multicentre, non-inferiority trial , 2018, British Medical Journal.

[29]  R. Sethi,et al.  Landmark Trials in Cardiology in 2017—Celebrating 40 Years of Angioplasty , 2018, International Journal of Angiology.

[30]  Deepak L. Bhatt,et al.  Ticagrelor versus clopidogrel after fibrinolytic therapy in patients with ST-elevation myocardial infarction: a systematic review and meta-analysis of randomized clinical trials , 2018, Journal of Thrombosis and Thrombolysis.

[31]  F. Crea,et al.  The year in cardiology 2017: acute coronary syndromes , 2018, European heart journal.

[32]  Diego Ardissino,et al.  Pharmacogenomic Approach to Selecting Antiplatelet Therapy in Patients With Acute Coronary Syndromes: The PHARMCLO Trial. , 2018, Journal of the American College of Cardiology.

[33]  Sherry‐Ann Brown,et al.  Pharmacogenomic Impact of CYP2C19 Variation on Clopidogrel Therapy in Precision Cardiovascular Medicine , 2018, Journal of personalized medicine.

[34]  J. Douketis,et al.  2018 Canadian Cardiovascular Society/Canadian Association of Interventional Cardiology Focused Update of the Guidelines for the Use of Antiplatelet Therapy. , 2017, The Canadian journal of cardiology.

[35]  P. Kolh,et al.  2017 ESC focused update on dual antiplatelet therapy in coronary artery disease developed in collaboration with EACTS. , 2018, European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery.

[36]  P. Bundhun,et al.  Head to head comparison of Prasugrel versus Ticagrelor in patients with acute coronary syndrome: a systematic review and meta-analysis of randomized trials , 2017, BMC Pharmacology and Toxicology.

[37]  Deepak L. Bhatt,et al.  Efficacy and Safety of Cangrelor in Preventing Periprocedural Complications in Patients With Stable Angina and Acute Coronary Syndromes Undergoing Percutaneous Coronary Intervention: The CHAMPION PHOENIX Trial. , 2016, JACC. Cardiovascular interventions.

[38]  Hachidai Takahashi,et al.  Impact of residual platelet reactivity under clopidogrel treatment for lesions and the clinical outcome after drug-eluting stent implantation in patients with hemodialysis. , 2016, Journal of cardiology.

[39]  M. Cattaneo,et al.  P2Y12 receptors: structure and function , 2015, Journal of thrombosis and haemostasis : JTH.

[40]  A. Jaffe,et al.  2014 AHA/ACC guideline for the management of patients with non-ST-elevation acute coronary syndromes: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. , 2014, Circulation.

[41]  Masafumi Ueno,et al.  Impaired responsiveness to the platelet P2Y12 receptor antagonist clopidogrel in patients with type 2 diabetes and coronary artery disease. , 2014, Journal of the American College of Cardiology.

[42]  A. Corsini,et al.  Pharmacology of the New P2Y12 Receptor Inhibitors: Insights on Pharmacokinetic and Pharmacodynamic Properties , 2013, Drugs.

[43]  O. Morel,et al.  Association of estimated GFR with platelet inhibition in patients treated with clopidogrel. , 2012, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[44]  N. Schork,et al.  Standard- vs high-dose clopidogrel based on platelet function testing after percutaneous coronary intervention: the GRAVITAS randomized trial. , 2011, JAMA.

[45]  S. Stevens,et al.  Ticagrelor vs. clopidogrel in patients with acute coronary syndromes and diabetes: a substudy from the PLATelet inhibition and patient Outcomes (PLATO) trial , 2010, European heart journal.

[46]  E. Antman,et al.  Greater Clinical Benefit of More Intensive Oral Antiplatelet Therapy With Prasugrel in Patients With Diabetes Mellitus in the Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition With Prasugrel–Thrombolysis in Myocardial Infarction 38 , 2008, Circulation.

[47]  Christopher P Cannon,et al.  Diabetes and mortality following acute coronary syndromes. , 2007, JAMA.

[48]  S. Husted New developments in oral antiplatelet therapy , 2007 .

[49]  M. Sabatine,et al.  Clopidogrel use in coronary artery disease , 2006, Expert review of cardiovascular therapy.

[50]  R. Collins,et al.  Addition of clopidogrel to aspirin in 45 852 patients with acute myocardial infarction: randomised placebo-controlled trial , 2005, The Lancet.

[51]  Eric J Topol,et al.  Early and sustained dual oral antiplatelet therapy following percutaneous coronary intervention: a randomized controlled trial. , 2002, JAMA.

[52]  P. R. R. Ecurrent,et al.  EFFECTS OF CLOPIDOGREL IN ADDITION TO ASPIRIN IN PATIENTS WITH ACUTE CORONARY SYNDROMES WITHOUT ST-SEGMENT ELEVATION , 2001 .