Abstract
Platelet aggregation and thrombus formation represent the basic mechanism for clinical,
electrocardiographic, and biomarker changes consistent with acute coronary syndrome.
Various oral and intravenous formulations of platelet function inhibitors have been
developed to help decrease platelet aggregation due to acute atherosclerotic plaque
rupture. In this article, we review the various mechanisms, pharmacokinetics/pharmacodynamics,
and the key clinical trials related to the platelet inhibitors that form the basis
for current recommendations of their use in the ST elevation myocardial infarction
guidelines by the American College of Cardiology/American Heart Association.
Keywords
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References
- Platelets as therapeutic targets to prevent atherosclerosis.Atherosclerosis. 2020; 307: 97-108
- Platelets in atherothrombosis.Mayo Clin Proc. 2006; 81: 59-68
- Patient management in the ICU: the PDB System.Proc Annu Symp Comput Appl Med Care. 1991; : 990-992
- Randomised trial of intravenous streptokinase, oral aspirin, both, or neither among 17,187 cases of suspected acute myocardial infarction: ISIS-2. ISIS-2 (Second International Study of Infarct Survival) Collaborative Group.Lancet. 1988; 2: 349-360
- Addition of clopidogrel to aspirin and fibrinolytic therapy for myocardial infarction with ST-segment elevation.N Engl J Med. 2005; 352: 1179-1189
- Addition of clopidogrel to aspirin in 45,852 patients with acute myocardial infarction: randomised placebo-controlled trial.Lancet. 2005; 366: 1607-1621
- Prasugrel versus clopidogrel in patients with acute coronary syndromes.N Engl J Med. 2007; 357: 2001-2015
- Prasugrel versus clopidogrel in patients with ST-segment elevation myocardial infarction according to timing of percutaneous coronary intervention: a TRITON-TIMI 38 subgroup analysis (Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition with Prasugrel-Thrombolysis In Myocardial Infarction 38).JACC Cardiovasc Interv. 2014; 7: 604-612
- Pharmacodynamics, pharmacokinetics, and safety of the oral reversible P2Y12 antagonist AZD6140 with aspirin in patients with atherosclerosis: a double-blind comparison to clopidogrel with aspirin.Eur Heart J. 2006; 27: 1038-1047
- Ticagrelor versus clopidogrel in patients With STEMI treated with fibrinolysis: TREAT trial.J Am Coll Cardiol. 2019; 73: 2819-2828
- Ticagrelor versus clopidogrel in patients with STEMI treated with thrombolysis: the MIRTOS trial.EuroIntervention. 2021; 16: 1163-1169
- Ticagrelor or prasugrel in patients with ST-segment-elevation myocardial infarction undergoing primary percutaneous coronary intervention.Circulation. 2020; 142: 2329-2337
- Initial aspirin dose and outcome among ST-elevation myocardial infarction patients treated with fibrinolytic therapy.Circulation. 2008; 117: 192-199
- Double-dose versus standard-dose clopidogrel and high-dose versus low-dose aspirin in individuals undergoing percutaneous coronary intervention for acute coronary syndromes (CURRENT-OASIS 7): a randomised factorial trial.Lancet. 2010; 376: 1233-1243
- Analysis of risk of bleeding complications after different doses of aspirin in 192,036 patients enrolled in 31 randomized controlled trials.Am J Cardiol. 2005; 95: 1218-1222
- Safety and efficacy of high- versus low-dose aspirin after primary percutaneous coronary intervention in ST-segment elevation myocardial infarction: the HORIZONS-AMI (Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction) trial.JACC Cardiovasc Interv. 2012; 5: 1231-1238
- Association of discharge aspirin dose with outcomes after acute myocardial infarction: insights from the treatment with ADP receptor inhibitors: longitudinal assessment of treatment patterns and events after acute coronary syndrome (TRANSLATE-ACS) study.Circulation. 2015; 132: 174-181
- 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines.Circulation. 2013; 127: e362-e425
- Pharmacokinetics of clopidogrel.Semin Thromb Hemost. 1999; 25: 25-28
- Pharmacokinetic profile of 14C-labeled clopidogrel.Semin Thromb Hemost. 1999; 25: 29-33
- P2Y(12) inhibitors: differences in properties and mechanisms of action and potential consequences for clinical use.Eur Heart J. 2009; 30: 1964-1977
- Reduced-function CYP2C19 genotype and risk of adverse clinical outcomes among patients treated with clopidogrel predominantly for PCI: a meta-analysis.JAMA. 2010; 304: 1821-1830
- Resistance to clopidogrel: a review of the evidence.J Am Coll Cardiol. 2005; 45: 1157-1164
- Bedside monitoring to adjust antiplatelet therapy for coronary stenting.N Engl J Med. 2012; 367: 2100-2109
- Clinical utility of CYP2C19 genotyping to guide antiplatelet therapy in patients with an acute coronary syndrome or undergoing percutaneous coronary intervention.Arterioscler Thromb Vasc Biol. 2019; 39: 647-652
- Standard- vs high-dose clopidogrel based on platelet function testing after percutaneous coronary intervention: the GRAVITAS randomized trial.JAMA. 2011; 305: 1097-1105
- A comparison of prasugrel and clopidogrel loading doses on platelet function: magnitude of platelet inhibition is related to active metabolite formation.Am Heart J. 2007; 153 (66.e9-16)
- Population pharmacokinetics and pharmacodynamics of prasugrel and clopidogrel in aspirin-treated patients with stable coronary artery disease.J Pharmacokinet Pharmacodyn. 2008; 35: 593-618
- Inhibition of platelet aggregation by AZD6140, a reversible oral P2Y12 receptor antagonist, compared with clopidogrel in patients with acute coronary syndromes.J Am Coll Cardiol. 2007; 50: 1852-1856
- Ticagrelor versus clopidogrel in patients with acute coronary syndromes.N Engl J Med. 2009; 361: 1045-1057
- Prasugrel versus ticagrelor in patients with acute myocardial infarction treated with primary percutaneous coronary intervention: multicenter randomized PRAGUE-18 study.Circulation. 2016; 134: 1603-1612
- Effect of clopidogrel pretreatment before percutaneous coronary intervention in patients with ST-elevation myocardial infarction treated with fibrinolytics: the PCI-CLARITY study.JAMA. 2005; 294: 1224-1232
- Prehospital ticagrelor in ST-segment elevation myocardial infarction.N Engl J Med. 2014; 371: 1016-1027
- Cangrelor: a review on pharmacology and clinical trial development.Expert Rev Cardiovasc Ther. 2013; 11: 1279-1291
- Cangrelor: an emerging therapeutic option for patients with coronary artery disease.Curr Med Res Opin. 2014; 30: 813-828
- Initial experience with an intravenous P2Y12 platelet receptor antagonist in patients undergoing percutaneous coronary intervention: results from a 2-part, phase II, multicenter, randomized, placebo- and active-controlled trial.Am Heart J. 2006; 151: 689.e1-689.e10
- Open multicentre study of the P2T receptor antagonist AR-C69931MX assessing safety, tolerability and activity in patients with acute coronary syndromes.Thromb Haemost. 2001; 85: 401-407
- Pharmacology of emerging novel platelet inhibitors.Am Heart J. 2008; 156: S10-S15
- Platelet inhibition with cangrelor in patients undergoing PCI.N Engl J Med. 2009; 361: 2318-2329
- Effect of platelet inhibition with cangrelor during PCI on ischemic events.N Engl J Med. 2013; 368: 1303-1313
- Effect of cangrelor on periprocedural outcomes in percutaneous coronary interventions: a pooled analysis of patient-level data.Lancet. 2013; 382: 1981-1992
- Platelet glycoprotein IIb/IIIa inhibition with coronary stenting for acute myocardial infarction.N Engl J Med. 2001; 344: 1895-1903
- Effects of platelet glycoprotein IIb/IIIa blockade with tirofiban on adverse cardiac events in patients with unstable angina or acute myocardial infarction undergoing coronary angioplasty. The RESTORE Investigators. Randomized Efficacy Study of Tirofiban for Outcomes and REstenosis.Circulation. 1997; 6: 1445-1453
- Comparison of angioplasty with infusion of tirofiban or abciximab and with implantation of sirolimus-eluting or uncoated stents for acute myocardial infarction: the MULTISTRATEGY randomized trial.JAMA. 2008; 299: 1788-1799
- Combined accelerated tissue-plasminogen activator and platelet glycoprotein IIb/IIIa integrin receptor blockade with Integrilin in acute myocardial infarction. Results of a randomized, placebo-controlled, dose-ranging trial. IMPACT-AMI Investigators.Circulation. 1997; 95: 846-854
- Prehospital high-dose tirofiban in patients undergoing primary percutaneous intervention. The AGIR-2 study.Arch Cardiovasc Dis. 2010; 103: 285-292
- Early initiation of eptifibatide in the emergency department before primary percutaneous coronary intervention for ST-segment elevation myocardial infarction: results of the Time to Integrilin Therapy in Acute Myocardial Infarction (TITAN)-TIMI 34 trial.Am Heart J. 2006; 152: 668-675
- Eptifibatide is noninferior to abciximab in primary percutaneous coronary intervention: results from the SCAAR (Swedish Coronary Angiography and Angioplasty Registry).J Am Coll Cardiol. 2010; 56: 470-475
- Intracoronary versus intravenous administration of abciximab in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention with thrombus aspiration: the comparison of intracoronary versus intravenous abciximab administration during emergency reperfusion of ST-segment elevation myocardial infarction (CICERO) trial.Circulation. 2010; 122: 2709-2717
- Intravenous platelet blockade with cangrelor during PCI.N Engl J Med. 2009; 361: 2330-2341
- Platelet inhibition with cangrelor and crushed ticagrelor in patients with ST-segment-elevation myocardial infarction undergoing primary percutaneous coronary intervention.Circulation. 2019; 139: 1661-1670
- Clinical use of cangrelor: nationwide experience from the Swedish Coronary Angiography and Angioplasty Registry (SCAAR).Eur Heart J Cardiovasc Pharmacother. 2019; 5: 151-157
- Platelet GPIIb/IIIa antagonists: the first anti-integrin receptor therapeutics.J Clin Invest. 1997; 99: 1467-1471
- The GPIIb/IIIa (integrin alphaIIbbeta3) odyssey: a technology-driven saga of a receptor with twists, turns, and even a bend.Blood. 2008; 112: 3011-3025
- A comparison of abciximab and small-molecule glycoprotein IIb/IIIa inhibitors in patients undergoing primary percutaneous coronary intervention: a meta-analysis of contemporary randomized controlled trials.Circ Cardiovasc Interv. 2009; 2: 230-236
- Randomized, double-blind, placebo-controlled dose-ranging study of tirofiban (MK-383) platelet IIb/IIIa blockade in high risk patients undergoing coronary angioplasty.J Am Coll Cardiol. 1996; 27: 536-542
- Immediate and reversible platelet inhibition after intravenous administration of a peptide glycoprotein IIb/IIIa inhibitor during percutaneous coronary intervention.Am J Cardiol. 1995; 76: 1222-1227
- Antiplatelet effects of abciximab, tirofiban and eptifibatide in patients undergoing coronary stenting.J Am Coll Cardiol. 2001; 37: 1323-1328
- Comparison of primary and facilitated percutaneous coronary interventions for ST-elevation myocardial infarction: quantitative review of randomised trials.Lancet. 2006; 367: 579-588
- Early vs late administration of glycoprotein IIb/IIIa inhibitors in primary percutaneous coronary intervention of acute ST-segment elevation myocardial infarction: a meta-analysis.JAMA. 2004; 292: 362-366
- Abciximab as adjunctive therapy to reperfusion in acute ST-segment elevation myocardial infarction: a meta-analysis of randomized trials.JAMA. 2005; 293: 1759-1765
- Abciximab in primary coronary stenting of ST-elevation myocardial infarction: a European meta-analysis on individual patients' data with long-term follow-up.Eur Heart J. 2007; 28: 443-449
- Randomized early versus late abciximab in acute myocardial infarction treated with primary coronary intervention (RELAx-AMI Trial).J Am Coll Cardiol. 2007; 49: 1517-1524
- Prehospital initiation of tirofiban in patients with ST-elevation myocardial infarction undergoing primary angioplasty (On-TIME 2): a multicentre, double-blind, randomised controlled trial.Lancet. 2008; 372: 537-546
- Facilitated percutaneous coronary intervention versus primary percutaneous coronary intervention: design and rationale of the Facilitated Intervention with Enhanced Reperfusion Speed to Stop Events (FINESSE) trial.Am Heart J. 2004; 147: E16
- 1-year survival in a randomized trial of facilitated reperfusion: results from the FINESSE (Facilitated Intervention with Enhanced Reperfusion Speed to Stop Events) trial.JACC Cardiovasc Interv. 2009; 2: 909-916
- Effect of early, pre-hospital initiation of high bolus dose tirofiban in patients with ST-segment elevation myocardial infarction on short- and long-term clinical outcome.J Am Coll Cardiol. 2010; 55: 2446-2455
- Randomized, placebo-controlled trial of platelet glycoprotein IIb/IIIa blockade with primary angioplasty for acute myocardial infarction. ReoPro and Primary PTCA Organization and Randomized Trial (RAPPORT) Investigators.Circulation. 1998; 98: 734-741
- Comparison of angioplasty with stenting, with or without abciximab, in acute myocardial infarction.N Engl J Med. 2002; 346: 957-966
- Early eptifibatide improves TIMI 3 patency before primary percutaneous coronary intervention for acute ST elevation myocardial infarction: results of the randomized integrilin in acute myocardial infarction (INTAMI) pilot trial.Eur Heart J. 2005; 26: 1971-1977
- Meta-analysis of prospective randomized controlled trials comparing intracoronary versus intravenous abciximab in patients with ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention.Am J Cardiol. 2012; 109: 624-628
- Intracoronary abciximab and aspiration thrombectomy in patients with large anterior myocardial infarction: the INFUSE-AMI randomized trial.JAMA. 2012; 307: 1817-1826
- Intracoronary versus intravenous bolus abciximab during primary percutaneous coronary intervention in patients with acute ST-elevation myocardial infarction: a randomised trial.Lancet. 2012; 379: 923-931
- Meta-analysis of randomized controlled trials comparing intracoronary and intravenous administration of glycoprotein IIb/IIIa inhibitors in patients with ST-elevation myocardial infarction.Am J Cardiol. 2012; 109: 1124-1130
- The optimal route of administration of the glycoprotein IIb/IIIa receptor antagonist abciximab during percutaneous coronary intervention; intravenous versus intracoronary.Curr Cardiol Rev. 2008; 4: 293-299
- Increase of myocardial salvage and left ventricular function recovery with intracoronary abciximab downstream of the coronary occlusion in patients with acute myocardial infarction treated with primary coronary intervention.Catheter Cardiovasc Interv. 2004; 62: 186-192
- Comparison of intracoronary vs. intravenous administration of abciximab in coronary stenting.Catheter Cardiovasc Interv. 2004; 61: 31-34
- Angiographic evaluation of the effect of intracoronary abciximab administration in patients undergoing urgent PCI.Int J Cardiol. 2005; 105: 250-255
- Reduction of major adverse cardiac events with intracoronary compared with intravenous bolus application of abciximab in patients with acute myocardial infarction or unstable angina undergoing coronary angioplasty.Circulation. 2003; 107: 1840-1843
- Intracoronary compared to intravenous Abciximab and high-dose bolus compared to standard dose in patients with ST-segment elevation myocardial infarction undergoing transradial primary percutaneous coronary intervention: a two-by-two factorial placebo-controlled randomized study.Am J Cardiol. 2010; 105: 1520-1527
- Abciximab in patients with acute ST-segment-elevation myocardial infarction undergoing primary percutaneous coronary intervention after clopidogrel loading: a randomized double-blind trial.Circulation. 2009; 119: 1933-1940
Article Info
Publication History
Published online: February 21, 2022
Footnotes
Funding: None.
Conflicts of Interest: None.
Authorship: Both authors had access to the data and a role in writing this manuscript.
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