ST-elevation myocardial infarction (STEMI) is considered a medical emergency globally, where the patient must seek medical help immediately. The treatment plan for this condition involves reperfusion therapy with or without stent placement, controlling the comorbidities and using specific medications to reduce the risk of recurrence and future complications.
One of the major drug categories is the antiplatelet therapy. So we will discuss briefly the different types of anti-platelet drugs used in STEMI and the different patient scenarios in STEMI. [1][2]
A-Antiplatelet Therapy to Support Primary PCI
1- Aspirin
– Loading Dose of 162 to 325 mg should be given before primary PCI, to be chewed or crushed to establish a high blood level quickly. (More rapid absorption occurs with non-enteric-coated formulations).
– After PCI, aspirin 81 -325 mg should be continued indefinitely (81 mg is the preferred dose)
2- P2Y12 receptor inhibitors
– A loading dose of a P2Y12 receptor inhibitor should be given as early as possible before or at time of primary PCI. Options include one of the following:
- Clopidogrel 600 mg
US FDA has highlighted the potential impact of CYP2C19 genotype on clopidogrel pharmacokinetics and clinical response ( e.g: drug interaction with PPI ) . Nevertheless, other studies have not confirmed associations è Future studies are needed to further clarify the risk .[3]
- Prasugrel 60 mg
NOT to be administered to patients with a history of stroke or transient ischemic attack and was not shown to be beneficial in patients ≥75 years of age or patients who weigh <60 kg.[4]
- Ticagrelor 180 mg
** Prasugrel and Ticagrelor are preferred to clopidogrel. [5] [6]
– P2Y12 inhibitor therapy should be given for at least 1 month in patients with BMS and at least 6 months in patient with DES, using the following maintenance doses: [2]
(( This duration can be extended or reduced according to the patient specific ischemic and bleeding risks )).
- Clopidogrel 75 mg daily
- Prasugrel 10 mg daily
- Ticagrelor 90 mg twice daily
3- GlycoProtein(GP) IIb/IIIa receptor antagonist
– these drugs are given at the time of primary PCI (with or without stenting or clopidogrel pre-treatment) in selected patients with STEMI who are receiving unfractionated heparin (UFH).
– patients who might benefit from a GP IIb/IIIa inhibitor include those who are found to have no or slow reflow, large thrombus burden, or intraprocedural bailout for distal embolization, coronary artery dissection, or hemodynamic instability.
Options include the following :
a.Abciximab:
-dose of 0.25-mg/kg IV bolus, then 0.125 mcg/kg/min (maximum 10 mcg/min)
b.high-bolus-dose Tirofiban :
– dose of 25-mcg/kg IV bolus, then 0.15 mcg/kg/min
– In patients with CrCl <30 mL/min, reduce infusion by 50%
c.Double-bolus Eptifibatide :
– dose of 180-mcg/kg IV bolus, then 2 mcg/kg/min; a second 180-mcg/kg bolus is administered 10 min after the first bolus.
– In patients with CrCl <50 mL/min, reduce infusion by 50%
– Avoid in patients on hemodialysis.
B-Antiplatelet Therapy With Fibrinolysis at a Non–PCI-Capable Hospital
1-Aspirin
– 162- to 325-mg loading dose
– should be continued indefinitely ( 81 mg is the preferred dose)
AND
2-P2Y12 receptor inhibitors
– Clopidogrel
– 300-mg loading dose for patients <= 75 years of age
– 75-mg loading dose for patients >75 years of age
– followed by: 75 mg daily should be continued for at least 14 days and up to 1 year
– prefer clopidogrel in this scenario over ticagrelor or prasugrel due to the increased risk of bleeding with the latter two. (( pretreatment with ticagrelor or prasugrel is considered a relative contraindication to fibrinolytic therapy )) [7]
C-Antiplatlet therapy when Transfer to a PCI-Capable Hospital After Fibrinolytic Therapy
1-Aspirin
– 162- to 325-mg loading dose
– 81- to 325-mg daily maintenance dose (indefinite)
– 81 mg daily is the preferred maintenance dose
2- P2Y12 receptor inhibitors
– Clopidogrel
– if the patient’s Age <= 75 years: 300-mg loading dose
– if the patient’s Age >75 years: no loading dose, give 75 mg
– Followed by 75 mg daily for at least 14 days and up to 1 year in absence of bleeding
D- Urgent CABG
1-Aspirin
– should not be withheld before urgent CABG
2- P2Y12 receptor inhibitors
– Clopidogrel or ticagrelor should be discontinued at least 24 hours before urgent on-pump CABG, if possible.
– Urgent CABG within 5 days of clopidogrel or ticagrelor administration or within 7 days of prasugrel administration might be considered, especially if the benefits of prompt revascularization outweigh the risks of bleeding.
3- GlycoProtein(GP) IIb/IIIa receptor antagonist
– Short-acting intravenous agents (eptifibatide, tirofiban) should be discontinued at least 2 to 4 hours before urgent CABG.
– Abciximab should be discontinued at least 12 hours before urgent CABG
– Urgent off-pump CABG within 24 hours of clopidogrel or ticagrelor administration might be considered, especially if the benefits of prompt revascularization outweigh the risks of bleeding.
The following table discusses some differences between P2Y12 receptor inhibitors.
|
P2Y12 receptor antagonist
|
Mechanism of binding |
Loading dose |
Maintenance dose |
Prodrug |
Comments |
|
Clopidogrel
|
Irreversible Inhibitor
|
300 mg or 600 mg |
75 mg once daily |
Yes
The drug needs to be metabolized into its active form |
-Warnings/Precautions: 1-Bleeding risk 2-Thienopyridine hypersensitivity 3-Thrombotic thrombocytopenic purpura (TTP) usually occurring within the first 2 weeks
– to be discontinued at least 5 days before surgery
|
|
Ticagrelor
|
Reversible inhibitor
|
180 mg |
90 mg twice daily |
No
|
-Warnings/Precautions: 1-Bleeding risk 2-Bradyarrhythmias and Ventricular pauses 3-Hyperuricemia 4-dyspnea 5-Thrombotic thrombocytopenic purpura (TTP) usually occurring within the first 2 weeks
– to be discontinued at ≥5 days before surgery.
|
|
Prasugrel
|
Irreversible inhibitor
|
60 mg |
10 mg once daily |
Yes
The drug needs to be metabolized into its active form |
-Warnings/Precautions:
1-Bleeding risk
[US Boxed Warning]: Do not use prasugrel in patients with active pathological bleeding or a history of TIA or stroke.
2-Hypersensitivity 3-Thrombotic thrombocytopenic purpura (TTP) usually occurring within the first 2 weeks
– to be discontinued at least 7 days before surgery
|
Table (1) : Summary of P2Y12 Receptor antagonist agents dosing, pharmacokinetics and adverse effects.
A special thank you to my sister, Rawan Ya’acoub, a clinical pharmacist and assistant professor at the University of Jordan, who helped me write this blog.
Reference:
[1]- 2013 ACCF/AHA Guideline for the Management of ST-Elevation Myocardial Infarction
[2]- 2016 ACC/AHA Guideline: Focused Update on Duration of Dual Antiplatelet Therapy in Patients With Coronary Artery Disease
[3]-Society for Cardiovascular Angiography and Interventions; Society of Thoracic Surgeons; Writing Committee Members, Holmes DR Jr, Dehmer GJ, Kaul S, Leifer D, O’Gara PT, Stein CM. ACCF/AHA Clopidogrel clinical alert: approaches to the FDA “boxed warning”: a report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents and the American Heart Association. Circulation. 2010 Aug 3;122(5):537-57. doi: 10.1161/CIR.0b013e3181ee08ed. Epub 2010 Jun 28. PMID: 20585015.
[4]-Wiviott SD, Braunwald E, McCabe CH, Montalescot G, Ruzyllo W, Gottlieb S, Neumann FJ, Ardissino D, De Servi S, Murphy SA, Riesmeyer J, Weerakkody G, Gibson CM, Antman EM; TRITON-TIMI 38 Investigators. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2007 Nov 15;357(20):2001-15. doi: 10.1056/NEJMoa0706482. Epub 2007 Nov 4. PMID: 17982182.
[5]-Wallentin L, Becker RC, Budaj A, Cannon CP, Emanuelsson H, Held C, Horrow J, Husted S, James S, Katus H, Mahaffey KW, Scirica BM, Skene A, Steg PG, Storey RF, Harrington RA; PLATO Investigators, Freij A, Thorsén M. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2009 Sep 10;361(11):1045-57. doi: 10.1056/NEJMoa0904327. Epub 2009 Aug 30. PMID: 19717846.
[6]-Wiviott SD, Braunwald E, McCabe CH, Montalescot G, Ruzyllo W, Gottlieb S, Neumann FJ, Ardissino D, De Servi S, Murphy SA, Riesmeyer J, Weerakkody G, Gibson CM, Antman EM; TRITON-TIMI 38 Investigators. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2007 Nov 15;357(20):2001-15. doi: 10.1056/NEJMoa0706482. Epub 2007 Nov 4. PMID: 17982182.
[7]- Sabatine MS, Cannon CP, Gibson CM, López-Sendón JL, Montalescot G, Theroux P, Claeys MJ, Cools F, Hill KA, Skene AM, McCabe CH, Braunwald E; CLARITY-TIMI 28 Investigators. Addition of clopidogrel to aspirin and fibrinolytic therapy for myocardial infarction with ST-segment elevation. N Engl J Med. 2005 Mar 24;352(12):1179-89. doi: 10.1056/NEJMoa050522. Epub 2005 Mar 9. PMID: 15758000.
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