Overview
ACS Management: Antiplatelet and Anticoagulation
Topic Overview
Summary
Antiplatelet and anticoagulation therapy are the cornerstone of acute coronary syndrome (ACS) management. Dual antiplatelet therapy (DAPT) with aspirin plus a P2Y12 inhibitor (clopidogrel, ticagrelor, or prasugrel) is standard. Parenteral anticoagulation (heparin, fondaparinux, or bivalirudin) is given acutely. Choice of agents depends on the type of ACS (STEMI vs NSTEMI), revascularisation strategy (PCI vs medical), and bleeding risk.
Key Facts
- Aspirin: 300 mg loading, then 75-100 mg daily (lifelong)
- P2Y12 inhibitor: Ticagrelor (180 mg load, 90 mg BD) or prasugrel (60 mg load, 10 mg OD) preferred; clopidogrel if contraindicated
- DAPT duration: 12 months post-ACS (shorter if high bleeding risk)
- Anticoagulation: UFH, LMWH (enoxaparin), or fondaparinux acutely
- STEMI + PPCI: UFH or bivalirudin at time of PCI
- NSTEMI: Fondaparinux preferred (unless high-risk PCI imminent)
Clinical Pearls
Ticagrelor is preferred over clopidogrel in NSTEMI/UA — faster onset, more potent, reversible
Prasugrel is contraindicated in prior stroke/TIA — increased bleeding risk
Fondaparinux is safer than enoxaparin for bleeding but needs UFH bolus at PCI
Why This Matters Clinically
Optimal antiplatelet and anticoagulation therapy reduces mortality, MI, and stent thrombosis. Getting the agents and timing right is critical.
Visual Summary
Visual assets to be added:
- DAPT choice algorithm
- Anticoagulation in ACS flowchart
- P2Y12 inhibitor comparison table
- Bleeding risk assessment tool
Epidemiology
Relevance
- ACS is one of the most common cardiovascular emergencies
- Antiplatelet therapy is standard of care
- Bleeding complications are a significant concern
Patient Selection Considerations
- Age (elderly higher bleeding risk)
- Weight (low weight = higher bleeding risk)
- Renal function (affects drug clearance)
- History of bleeding
- Prior stroke/TIA (affects prasugrel use)
Pathophysiology
Platelet Activation in ACS
- Plaque rupture → exposure of subendothelial matrix
- Platelet adhesion, activation, aggregation
- Thrombus formation → coronary occlusion
Antiplatelet Mechanisms
| Drug | Mechanism |
|---|---|
| Aspirin | Irreversible COX-1 inhibition → blocks TXA2 |
| Clopidogrel | Irreversible P2Y12 inhibition (prodrug) |
| Ticagrelor | Reversible P2Y12 inhibition (direct acting) |
| Prasugrel | Irreversible P2Y12 inhibition (prodrug, faster onset) |
Anticoagulation Mechanisms
| Drug | Mechanism |
|---|---|
| UFH | Activates antithrombin → inhibits IIa and Xa |
| Enoxaparin | LMWH; mainly anti-Xa |
| Fondaparinux | Selective factor Xa inhibitor |
| Bivalirudin | Direct thrombin inhibitor |
Clinical Presentation
When to Initiate Therapy
Red Flags (Contraindications)
| Finding | Significance |
|---|---|
| Active bleeding | Delay/avoid anticoagulation |
| Recent intracranial haemorrhage | Absolute contraindication |
| Severe thrombocytopenia | Increased risk |
| Prior stroke/TIA | Prasugrel contraindicated |
| Need for CABG | Consider clopidogrel (shorter offset) |
As soon as ACS is suspected (in ED or pre-hospital)
Common presentation.
Aspirin given immediately
Common presentation.
P2Y12 inhibitor given after diagnosis confirmed (or at PCI)
Common presentation.
Anticoagulation started on admission
Common presentation.
Clinical Examination
Assess Bleeding Risk
- Signs of active bleeding
- Bruising
- Previous bleeding history
- Assess for anaemia
Cardiovascular Assessment
- Heart failure signs (may affect drug choice)
- Shock (may need parenteral only initially)
Investigations
Baseline Bloods
| Test | Purpose |
|---|---|
| FBC | Baseline Hb, platelets |
| Coagulation | PT, APTT (for UFH monitoring) |
| U&E, creatinine | Renal function (dose adjustment) |
| LFTs | Baseline |
During Treatment
- APTT (if on UFH infusion)
- Platelet count (heparin-induced thrombocytopenia risk)
- Hb (monitor for bleeding)
Classification & Staging
By ACS Type
| Type | Preferred Antiplatelet | Preferred Anticoagulation |
|---|---|---|
| STEMI (PPCI) | Aspirin + ticagrelor or prasugrel | UFH or bivalirudin at PCI |
| NSTEMI (high risk) | Aspirin + ticagrelor | Fondaparinux (or enoxaparin) |
| NSTEMI (low risk) | Aspirin + ticagrelor or clopidogrel | Fondaparinux |
| UA | Aspirin + ticagrelor or clopidogrel | Fondaparinux |
By Bleeding Risk
| Risk | Strategy |
|---|---|
| High bleeding risk | Shorter DAPT (3-6 months), consider clopidogrel |
| Standard risk | 12 months DAPT |
| High ischaemic risk | Extended DAPT (beyond 12 months) |
Management
Antiplatelet Therapy
Aspirin:
- Loading: 300 mg (chewed for rapid absorption)
- Maintenance: 75-100 mg OD (lifelong)
P2Y12 Inhibitors:
| Drug | Loading | Maintenance | Notes |
|---|---|---|---|
| Ticagrelor | 180 mg | 90 mg BD | Preferred in NSTEMI; reversible |
| Prasugrel | 60 mg | 10 mg OD | Use with PCI; CI in stroke/TIA |
| Clopidogrel | 300-600 mg | 75 mg OD | Alternative if others contraindicated |
DAPT Duration:
- Standard: 12 months
- Short (3-6 months): High bleeding risk
- Extended (beyond 12 months): High ischaemic risk, well-tolerated
Anticoagulation
STEMI + PPCI:
- UFH: 70-100 units/kg bolus at PCI
- Bivalirudin: Alternative (especially if high bleeding risk)
NSTEMI:
- Fondaparinux 2.5 mg SC OD (preferred — lower bleeding)
- Enoxaparin 1 mg/kg BD (if high-risk, early invasive planned)
- UFH infusion (if CABG planned)
At PCI (for fondaparinux patients):
- Add UFH bolus (to prevent catheter thrombosis)
Special Situations
| Situation | Approach |
|---|---|
| Renal impairment | Dose-adjust enoxaparin; avoid fondaparinux if CrCl under 20 |
| Need for CABG | Stop ticagrelor 3 days, clopidogrel 5 days, prasugrel 7 days before |
| Oral anticoagulation (AF) | Triple therapy initially, then dual pathway |
Complications
Of Antiplatelet/Anticoagulation
- Bleeding (GI, intracranial, access site)
- Thrombocytopenia (HIT with heparin)
- Dyspnoea (ticagrelor)
- Allergic reactions
Of Under-treatment
- Stent thrombosis
- Recurrent MI
- Death
Prognosis & Outcomes
Benefits of Optimal Therapy
- Reduced mortality
- Reduced recurrent MI
- Reduced stent thrombosis
Bleeding Risk
- Major bleeding associated with increased mortality
- Balance ischaemic and bleeding risk
Evidence & Guidelines
Key Guidelines
- ESC Guidelines on Acute Coronary Syndromes (2023)
- NICE NG185: Acute Coronary Syndromes
Key Trials
| Trial | Finding |
|---|---|
| PLATO | Ticagrelor superior to clopidogrel in ACS |
| TRITON-TIMI 38 | Prasugrel superior to clopidogrel in PCI |
| OASIS-5 | Fondaparinux safer than enoxaparin |
| HORIZONS-AMI | Bivalirudin reduces bleeding vs UFH+GPI |
Patient & Family Information
Why Do I Need These Medications?
After a heart attack or unstable angina, blood-thinning medications help prevent blood clots forming in your heart arteries and stents.
What Medications Will I Take?
- Aspirin: Daily for life
- A second blood thinner (ticagrelor, prasugrel, or clopidogrel): Usually for 12 months
Side Effects
- Increased risk of bleeding (bruising, nosebleeds)
- Ticagrelor can cause shortness of breath
- Report any unusual bleeding immediately
Important Advice
- Do not stop these medications without speaking to your doctor
- Tell any healthcare professional you are on blood thinners before procedures
Resources
References
Primary Guidelines
- Byrne RA, et al. 2023 ESC Guidelines for the management of acute coronary syndromes. Eur Heart J. 2023;44(38):3720-3826. PMID: 37622654
Key Trials
- Wallentin L, et al. Ticagrelor versus clopidogrel in patients with acute coronary syndromes (PLATO). N Engl J Med. 2009;361(11):1045-1057. PMID: 19717846
- Yusuf S, et al. Comparison of fondaparinux and enoxaparin in acute coronary syndromes (OASIS-5). N Engl J Med. 2006;354(14):1464-1476. PMID: 16537663