Introduction
Antiplatelet and anticoagulant medications for STEMI
Classification of anticoagulants (Tab. 1)
-
vorapaxar
-
rivaroxaban
UFH | Enoxaparin | Bivalirudin | |
---|---|---|---|
Administration route | Intravenous | Intravenous, subcutaneous | Intravenous |
Factor Xa:IIa inhibition | 1:1 | 3–4:1 | Only IIa |
Action independent of antithrombin | No | No | Yes |
Nonspecific binding | Yes | Partial | No |
Variable PK/PD measures | Yes | Yes (<unfractionated heparin) | No |
Inhibits fibrin-bound thrombin | No | No | Yes |
Effect on platelets | Activation | Activation | Inhibition |
Half-life | ~60 min | 90–120 min | 25 min |
Risk of HITT | Yes | Yes (<unfractionated heparin) | No |
Dose in PPCI | 70–100 U/kg bolus without GPIs; 50–70 U/kg bolus with GPIs | 0.5 mg/kg intravenous bolus | 0.75 mg/kg intravenous bolus; 1.75 mg/kg/h infusion |
Reversal agent | Protamine sulfate | No | No |
Classification of antiplatelet agents
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clopidogrel, prasugrel (irreversible inhibitors)
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cangrelor and ticagrelor (reversible inhibitors)
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tirofiban, abciximab, eptifibatide
Anticoagulant therapy before and during primary PCI
Unfractionated heparin
Low-molecular-weight heparin
Bivalirudin
HORIZONS-AMI | EUROMAX | HEAT-PPCI | BRIGHT | MATRIX-STEMI | |
---|---|---|---|---|---|
Trial design
| |||||
Patient population | 3,602 STEMI undergoing PPCI | 2,218 STEMI transported for PPCI | 1,812 STEMI undergoing PPCI | 2,194 acute MI undergoing emergency PCI (87.7% STEMI) | 4,010 STEMI undergoing PPCI |
Type of heparin | UFH | UFH or enoxaparin | UFH | UFH | UFH |
Heparin dose | 60 U/kg with subsequent boluses targeted to ACT of 200–250 s | UFH: 100 U/kg without GPI or 60 U/kg with GPI. Enoxaparin: 0.5 mg/kg | 70 U/kg | 100 U/kg in UFH-only group; 60 U/kg in heparin plus tirofiban group | 70–100 U/kg without GPI or 50–70 U/kg with GPI |
GPI use in heparin group | Routine (97.7% of patients) | Routine or bailout (69% of patients) | Bailout (14% of patients) | Bailout (5.6% of patients) in UFH-only group; routine (100%) in UFH plus tirofiban group | Routine or bailout (25.9% of patients) |
GPI use in bivalirudin group | Bailout (7.5% of patients) | Bailout (11.5% of patients) | Bailout (14% of patients) | Bailout (4.4% of patients) | Bailout (4.6% of patients) |
Post-PCI bivalirudin infusion | None (but could be continued at low doses if clinically indicated) | 4 h after PCI at 0.25 mg/kg/h; continuation of PCI dose was also permitted (22.5%) | None | 30 min–4 h after PCI (mean 180 min) at PCI dose | Patients randomised 1:1 to receive or not receive post-PCI infusion (full dose for up to 4 h or reduced dose of 0.25 mg/kg/h for ≥6 h) |
P2Y12 receptor inhibitor | Clopidogrel 300–600 mg | Clopidogrel (50%), prasugrel (30%), or ticagrelor (20%) | Clopidogrel (11%), prasugrel (27%), or ticagrelor (62%) | Clopidogrel 300–600 mg | Clopidogrel (29%), prasugrel (31%), or ticagrelor (30%) |
Radial access | No | 47% of patients | 81% of patients | 78% of patients | 50% (randomised 1:1 to radial versus femoral) |
Primary end point | NACE (major bleeding or MACE [death, reinfarction, TVR for ischaemia, and stroke]) at 30 days; non-CABG-related major bleeding at 30 days | Death or non-CABG-related major bleeding at 30 days | Efficacy: MACE (all-cause death, CVA, reinfarction, or additional unplanned TLR) at 28 days. Safety: major bleeding at 28 days | NACE (MACE [all-cause death, reinfarction, ischaemia-driven TVR, or stroke] or any bleeding) at 30 days | MACE (death, MI, or stroke) at 30 days; NACE (MACE or major bleeding) at 30 days |
Bleeding definition | Protocol-defined | Protocol-defined | BARC type 3–5 | BARC | BARC type 3 or 5 |
Study results
| |||||
Primary end point(s) | NACE: bivalirudin 9.2% vs. UFH 12.1% (P = 0.005); non-CABG-related major bleeding: bivalirudin 4.9% vs. UFH 8.3% (P < 0.001) | Bivalirudin 5.1% vs. UFH 8.5% (P = 0.001) | MACE: bivalirudin 8.7% vs. UFH 5.7% (P = 0.02); major bleeding: bivalirudin 3.5% vs. UFH 3.1% (P = 0.59) | Bivalirudin 8.8% vs. heparin 13.2% vs. UFH plus tirofiban 17.0% (P < 0.001) | MACE: bivalirudin 5.9% vs. UFH 6.5% (P = 0.43); NACE: bivalirudin 7.0% vs. UFH 8.2% (P = 0.13) |
MACE | Bivalirudin 5.4% vs. UFH 5.5% (P = 0.95) | Bivalirudin 6.0% vs. UFH 5.5% (P = 0.64) | See primary end point | Bivalirudin 5.0% vs. UFH 5.8% vs. UFH plus tirofiban 4.9% (P = 0.83) | See primary end point |
Major bleeding | See primary end point | Bivalirudin 2.6% vs. UFH 6.0% (P < 0.001) | See primary end point | BARC type 3–5: bivalirudin 0.5% vs. UFH 1.5% vs. UFH plus tirofiban 2.1% (P = NA) | Bivalirudin 1.7% vs. UFH 2.8% (P = 0.019) |
Acute stent thrombosis (≤24 h) | Bivalirudin 1.3% vs. UFH 0.3% (P < 0.001) | Bivalirudin 1.1% vs. UFH 0.2% (P = 0.007) | Bivalirudin 2.9% vs. UFH 0.9% (P = 0.007) | Bivalirudin 0.3% vs. UFH 0.3% vs. UFH plus tirofiban 0.3% (P = NA) | Bivalirudin 0.9% vs. UFH 0.5% (P = 0.10) |
Antiplatelet therapy before and during primary PCI
Aspirin
Aspirin | Clopidogrel | Prasugrel | Ticagrelor | Vorapaxar | Rivaroxaban | |
---|---|---|---|---|---|---|
Target | COX1 | P2Y12 receptor | P2Y12 receptor | P2Y12 receptor | PAR1 | Factor Xa |
Type of blockade | Irreversible | Irreversible | Irreversible | Reversible | Reversible | Reversible |
Dose | 150–325 mg LD; 81–100 mg once-daily MD | 600 mg LD; 75 mg once-daily MD | 60 mg LD; 10 mg once-daily MD | 180 mg LD; 90 mg twice-daily MD | 2.08 mg once-daily MD | 2.5 mg twice-daily MD |
Prodrug | No | Yes | Yes | No | No | No |
Onset of action | 60 min | 2–8 h | 30 min–4 h | 30 min–4 h | >12 h|| | 2–4 h |
Offset of action | 7–10 days | 7–10 days | 7–10 days | 3–5 days | 4–8 weeks | 12 h |
Drug interactions | NSAIDs | CYP2C19 inhibitors | No | CYP3A inhibitors or inducers, drugs using P‑glycoprotein transporter | CYP3A inhibitors or inducers, drugs using P‑glycoprotein transporter | CYP3A4 inhibitors or inducers, P‑glycoprotein transporter inhibitors |
Timing of administration | Immediately after presentation | At presentation or at time of primary PCI | At presentation or at time of primary PCI | At presentation or at time of primary PCI | After stabilisation | After stabilisation (>24 h after admission) |
Contraindications | Hypersensitivity | Hypersensitivity, active pathological bleeding | Prior CVA, high risk of bleeding, hypersensitivity | Prior ICH, high risk of bleeding, severe hepatic dysfunction, hypersensitivity | Prior ICH or CVA, high risk of bleeding, hypersensitivity | Prior CVA, CrCl <15 ml/min, high bleeding risk, severe hepatic dysfunction, treatment with other anticoagulant, hypersensitivity |
P2Y12 receptor inhibitors
Abciximab | Eptifibatide | Tirofiban | |
---|---|---|---|
Trade name | ReoPro | Integrilin | Aggrastat |
Molecule | Fragment antigen binding (Fab) 7E3 | Synthetic peptide | Non-peptide mimetic |
Molecular weight (Da) | ~50,000 | ~800 | ~500 |
Stoichiometry (drug to glycoprotein IIb/IIIa) | ~1.5:1 | >>100:1 | >>100:1 |
Binding | Non-competitive | Competitive | Competitive |
Half-life (h) | Plasma: 10–15 | Plasma: 2.0–2.5 | Plasma: 2.0–2.5 |
Biologic: 12–24 | Biologic = plasma | Biologic = plasma | |
PCI dosing | Bolus: 250 μg/kg | Bolus: 180 μg/kg* plus 180 μg/kg (after 10 min) | Bolus: 25 μg/kg |
Infusion: 0.125 μg/kg/min (12 h) | Infusion: 2 μg/kg/min (12–24 h)‡ | Infusion: 0.15 μg/kg/min (up to 18 h) | |
Renal adjustment | No | Bolus: 180 μg/kg | Bolus: 25 μg/kg |
Infusion: 1 μg/kg/min (12–24 h) | Infusion: 0.075 μg/kg/min (up to 18 h) |