Newer antiplatelet drugs
1. Newer P2Yโโ (ADP) Receptor Inhibitors
Prasugrel
- Type: Irreversible thienopyridine
- Onset: Rapid, predictable
- Potency: Greater platelet inhibition than clopidogrel
- Key trials: TRITONโTIMI 38
- Clinical use: ACS undergoing PCI
- Major limitations:
- Contraindicated in prior stroke/TIA
- Caution if age โฅ75 years or weight <60 kg
- Exam pearl: Lower stent thrombosis, higher bleeding than clopidogrel
Ticagrelor
- Type: Reversible, non-thienopyridine
- Onset/offset: Rapid on and off
- Key trials: PLATO, PEGASUS-TIMI 54
- Advantages:
- No hepatic activation
- Effective irrespective of CYP polymorphism
- Adverse effects:
- Dyspnea
- Bradyarrhythmias
- โ Uric acid
- Unique feature: Twice-daily dosing
- Exam pearl: Mortality benefit over clopidogrel in ACS
Cangrelor
- Type: Intravenous, reversible P2Yโโ inhibitor
- Onset: Immediate (seconds)
- Offset: Platelet function recovers within 60 minutes
- Key trial: CHAMPION PHOENIX
- Clinical niche:
- Cath lab use
- Patients not pre-loaded orally
- Exam pearl: Bridge therapy when oral P2Yโโ not feasible
2. Protease-Activated Receptor-1 (PAR-1) Antagonist
Vorapaxar
- Mechanism: Thrombin receptor (PAR-1) inhibition
- Key trials: TRA 2ยฐPโTIMI 50
- Indication: Secondary prevention in stable atherosclerotic disease
- Major risk: Intracranial hemorrhage
- Contraindication: Prior stroke, TIA, or ICH
- Exam pearl: Never used in acute ACS phase
3. Glycoprotein IIb/IIIa Inhibitors (Parenteral โ โOlder but Advancedโ)
(Still considered high-end antiplatelet therapy)
| Drug | Type | Use |
|---|---|---|
| Abciximab | Monoclonal antibody | Bail-out PCI |
| Eptifibatide | Peptide | High thrombus burden |
| Tirofiban | Non-peptide | STEMI with no-reflow |
Trend: Declining use due to bleeding risk and potent oral P2Yโโ agents.
4. Emerging / Investigational Antiplatelet Agents
Selatogrel
- Type: Subcutaneous P2Yโโ inhibitor
- Onset: Very rapid
- Current status: Phase III trials
- Potential role: Early self-administration in ACS
Rucaparib-like GPVI inhibitors (e.g., Glenzocimab)
- Target: GPVIโcollagen pathway
- Theoretical advantage: Antithrombotic effect with less bleeding
- Status: Early clinical trials
5. Practical Clinical Hierarchy (Current Practice)
- ACS + PCI:
Ticagrelor / Prasugrel > Clopidogrel - Cath lab, no oral loading:
Cangrelor - Stable CAD / PAD (selected):
Vorapaxar (rare, highly selected) - High bleeding risk:
Prefer clopidogrel or de-escalation strategies
6. High-Yield Exam Summary Table
| Drug | Reversible | Route | Mortality Benefit | Key Risk |
|---|---|---|---|---|
| Prasugrel | No | Oral | No | Bleeding |
| Ticagrelor | Yes | Oral | Yes | Dyspnea |
| Cangrelor | Yes | IV | No | Cost |
| Vorapaxar | No | Oral | No | ICH |
