Table 1. Antiagregant treatment in acute coronary syndromes.
| Drugs | Salicylate |
Thienopyridine |
Thienopyridine |
Triazolopyrimidine |
ATP analogue |
GPIIb/IIIa inhibitors |
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| Aspirin | Clopidogrel | Prasugrel | Ticagrelor | Cangrelor | Abciximab (REOPRO) | Eptifibatide (INTEGRILIN) | Tirofiban (AGGRASTAT) | |
| Indications | Primary prevention. Secondary prevention, invasive or conservatory strategy for STEMI/NSTEMI | Invasive or conservatory strategy for STEMI/NSTEMI if prasugrel or ticagrelor not available or if oral anticoagulation required | Invasive strategy for STEMI/NSTEMI | Invasive strategy for STEMI/invasive or conservatory strategy for NSTEMI | Invasive strategy for STEMI/NSTEMI | Invasive strategy for STEMI/NSTEMI, indicated in bailout situations/large thrombus burden | ||
| Pretreatment (before cath lab) | In STEMI: yes In NSTEMI: yes |
In STEMI: yes In NSTEMI: Unknown (both before or during PCI accepted) |
In STEMI: no In NSTEMI: no |
In STEMI: no In NSTEMI: Unknown (both before or during PCI accepted) |
In NSTEMI: Unknown (both before or after PCI accepted) | Never before PCI | ||
| Mechanism | COX1-irreversible inactivation | ADP-induced platelet activation inhibition by P2Y12 irreversible receptor inactivation | ADP-induced platelet activation inhibition by P2Y12 irreversible receptor inactivation | P2Y12 reversible receptor inactivation | ATP analogue, reversible | GPIIb/IIIa inhibitors (fibrinogen inhibition) | ||
| Pharmacokinetics | ||||||||
| Loading dose effect | 15–30 min | IE after 4–7 days if 75 mg/day IE after 3–6 h if 300 mg (peak in 24–48 h) Peak in 2 h after 600 mg |
30 min | 30 min | 2 min | Peak in 2 h after bolus | Peak in 2 h after bolus | Peak in 2 h after bolus |
| Duration of loading dose | 10 days | 4–8 days: 5 days the average | 5–10 days | 3–4 days | 1–2 h | 48 h | 4–8 h | 4–8 h |
| Stop before major surgery | 10 days | 5 days | 7 days | 3–5 days | 1 h | 48 h | 4–8 h | 4–8 h |
| Plasma half life | 20 min | 30–60 min | 30–60 min | 6–12 h | 5–10 min | 10–30 min Affinity for receptor is moderate-high |
2–3 h Affinity for receptor is low |
2 h Affinity for receptor is moderate |
| Dosage | ||||||||
| Dosage in PCI strategy | Loading: 150–300 mg (p.o.) or 75–150 mg (i.v.) Maintenance: 75–100 mg/day |
Loading: 300–600 mg (p.o.) Maintenance: 75 mg/day |
Loading: 60 mg (p.o.) Maintenance: 10 mg/day |
Loading: 180 mg (p.o.) Maintenance: 90 mg twice daily |
Loading: 30 µg/kg (i.v.) Maintenance: 4 µg /kg per minute (i.v.) |
Loading: 250 µg/kg (i.v.) Maintenance: 0.125µg/kg per minute (max. 10 mcg/min) (i.v.) for 12 h |
Loading: 180 µg/kg (i.v.) Maintenance: 2 µg/kg per minute (i.v.) for 18 h |
Loading: 25 µg/kg or 10 µg/kg (i.v.) Maintenance: 0.15 µg/kg per minute (i.v.) for 18 h |
| Dosage in conservative strategy | Same as above | Same as above | Not recommended (unknown anatomy) | Same as above | Not recommended | Not recommended | Not recommended | Not recommended |
| Dosage in thrombolysis | Same as above | Loading: 300 mg (oral) if < 75 yrs Maintenance: 75 mg/day |
Not recommended (unknown anatomy) | Not recommended | Not recommended | Not recommended | Not recommended | Not recommended |
| Dosage in renal failure | No adjustement | No adjustement | eGFR < 15 mL/1.73 m2 per minute: not recommended | eGFR < 15 mL/1.73 m2 per minute: not recommended | eGFR < 15 mL/1.73 m2 per minute: not recommended | No specific recommendation | eGFR: 30-50 mL/1.73 m2 per minute: Loading: 180 µg/kg (i.v.), Maintenance: 1 µg/kg per minute (i.v.). eGFR < 30 mL/1.73 m2 per minute: not recommended |
eGFR: 15-29 mL/1.73 m2 per minute: Loading: 25 µg/kg or 10 µg/kg (i.v.), Maintenance: 0.05 µg/kg/min (i.v.) eGFR < 15 mL/1.73 m2 per minute: not recommended |
| Dosage in elderly (> 75 yrs) | Loading: same Maintenance: 75 mg/day (lowest dose effective) |
No adjustement No loading if thrombolysis |
Maintenance: 5mg/day. No role of platelet function testing. |
No adjustement | No adjustement | Use with caution if >70 yrs | Use with caution if > 70 yrs | Use with caution if > 70 yrs |
| Trials | ISIS-2 GISSI-2 RISC |
CAPRIE, CURE, PCI-CURE, CREDO | TRITON-TIMI 38 TRILOGY ACS | PLATO | CHAMPION-PCI CHAMPION-PLATFORM CHAMPION-PHOENIX | CAPTURE, EPIC, EPILOG, EPISTENT, GUSTO4-ACS, ADMIRAL, ACE | IMPACT-II, PURSUIT, ESPIRIT | PRISM, RESTORE, TARGET, TACTICS |
| Contraindications and adverse effects | ||||||||
| Contraindications | Active bleeding | Active bleeding | Prior stroke or TIA Severe hepatic disease Active bleeding |
Prior intracranial hemorrage; Severe hepatic disease Active bleeding |
Active bleeding | Active bleeding Pre-existing thrombocytopenia Prior stroke (in the last 2 years for abciximab and in the last 30 days for eptifibatide and tirofiban) Concomitent thrombolysis in STEMI |
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| Adverse effects | Gastrointestinal bleeding | Neutropenia (0.02%–0.1%) Prurit Urticaria |
Bleeding | Dyspnea Bradycardia Increase in uric acid |
Bleeding | Thrombocytopenia (2%) Severe thrombocytopenia (0.5–1%) |
Thrombocytopenia (0.3–0.5%) | Thrombocytopenia (0.3–0.5%) |
ADP: adenozine diphosphate; COX: cyclooxygenase; GPIIb/IIIa: glycoprotein IIb/IIIa; IE: inhibitory effect; NSTEMI: non-ST-elevated myocardial infarction; PCI: percutaneous coronary interventions; STEMI: ST-elevated myocardial infarction; TIA: trainsient ischemic attack.