What is the recommended antiplatelet (anti-platelet) therapy in patients with acute coronary syndrome (ACS)?

Antiplatelet Therapy in Acute Coronary Syndrome

Primary Recommendation

All patients with acute coronary syndrome should receive dual antiplatelet therapy (DAPT) consisting of aspirin (75-100 mg daily) plus ticagrelor (180 mg loading dose, then 90 mg twice daily) as first-line therapy for 12 months, unless contraindications or excessive bleeding risk exist. 1, 2

P2Y12 Inhibitor Selection Algorithm

First-Line: Ticagrelor

• Ticagrelor is the preferred P2Y12 inhibitor for all ACS patients regardless of initial treatment strategy (medical management, PCI, or CABG). 1, 2
• Administer 180 mg loading dose followed by 90 mg twice daily. 1
• Ticagrelor can be used in patients with prior stroke or TIA, unlike prasugrel. 1
• If patients are already on clopidogrel, switch to ticagrelor immediately with a 180 mg loading dose regardless of clopidogrel timing or dose. 1, 2

Second-Line: Prasugrel

• Prasugrel (60 mg loading dose, then 10 mg daily) is an alternative for P2Y12 inhibitor-naïve patients with NSTE-ACS or STEMI undergoing PCI. 1, 3
• Prasugrel is absolutely contraindicated in patients with prior stroke or TIA due to increased cerebrovascular event risk (6.5% vs 1.2% with clopidogrel). 1, 4
• Consider dose reduction to 5 mg daily in patients weighing <60 kg due to increased bleeding risk, though this dose has not been prospectively validated. 3
• Avoid in patients >75 years old. 4
• Do not use prasugrel in medically managed ACS patients (only for those undergoing PCI). 1

Third-Line: Clopidogrel

• Clopidogrel (600 mg loading dose, then 75 mg daily) should only be used when ticagrelor or prasugrel are contraindicated. 1, 2
• Specific indications for clopidogrel include: prior intracranial bleeding, need for oral anticoagulation (triple therapy), excessive bleeding risk (PRECISE-DAPT score ≥25), or prolonged prothrombin time. 1, 5
• Using clopidogrel as first-line therapy when ticagrelor or prasugrel are available represents suboptimal care. 2

Aspirin Dosing

• Maintain aspirin at 75-100 mg daily when used with DAPT. 1, 2
• When using ticagrelor specifically, the American College of Cardiology recommends 81 mg daily rather than higher doses. 1
• Higher aspirin doses increase bleeding without improving efficacy. 5

Standard Duration: 12 Months

• The default DAPT duration is 12 months for all ACS patients who are not at high bleeding risk, regardless of ACS type (STEMI, NSTEMI, unstable angina), stent type, or completeness of revascularization. 1, 2
• This recommendation persists despite recent evidence questioning whether 12 months is truly optimal, as it remains the only Class I guideline recommendation. 6

Shortened Duration (6 Months)

• Consider 6-month DAPT duration in patients with excessive bleeding risk (PRECISE-DAPT score ≥25). 1, 5
• High bleeding risk is defined as 1-year risk of serious bleeding ≥4% or intracranial hemorrhage risk ≥1%. 4
• High-risk patients include those ≥65 years old, BMI <18.5, diabetes, prior bleeding, or on oral anticoagulants. 4

Prolonged Duration (>12 Months)

• May be considered in patients at low bleeding risk and high ischemic risk, though optimal duration beyond 1 year is not well established. 4

Bleeding Risk Mitigation Strategies

Mandatory Interventions

• Prescribe a proton pump inhibitor (PPI) with DAPT in all patients to reduce gastrointestinal bleeding risk. 1, 2, 5
• Use radial over femoral artery access for coronary angiography and PCI when performed by an expert radial operator. 1, 2, 5

Timing Considerations

• In NSTE-ACS patients with angiography delayed >24 hours, upstream treatment with clopidogrel or ticagrelor may be considered to reduce major adverse cardiovascular events. 2
• However, in a trial of 4,033 NSTEMI patients, no clear benefit was observed when prasugrel loading dose was administered prior to diagnostic angiography compared to at time of PCI, while bleeding risk increased with early administration. 3

De-escalation Strategies After Initial Period

Ticagrelor Monotherapy

• For patients who have tolerated DAPT with ticagrelor without bleeding, transition to ticagrelor monotherapy (discontinue aspirin) ≥1 month after PCI. 1, 2
• Recent evidence suggests discontinuing aspirin rather than the P2Y12 inhibitor may be associated with better outcomes. 4

Triple Therapy Patients

• For patients requiring long-term anticoagulation, discontinue aspirin 1-4 weeks after PCI and continue P2Y12 inhibitor, preferably clopidogrel rather than ticagrelor due to significantly lower bleeding risk. 1, 2

Guided vs. Unguided De-escalation

• De-escalation strategies (switching from prasugrel/ticagrelor to clopidogrel, dose reduction, or shortening DAPT duration) reduce bleeding without increasing ischemic events. 7
• Unguided de-escalation has more prominent bleeding reduction compared to guided de-escalation. 7

Perioperative Management

• Continue aspirin perioperatively if bleeding risk allows. 1
• Do not discontinue DAPT within the first month after stent placement for elective non-cardiac surgery, as this dramatically increases stent thrombosis risk. 1, 2
• Resume antiplatelet therapy as soon as possible post-operatively. 1

Critical Pitfalls to Avoid

• Never use clopidogrel as first-line therapy when ticagrelor or prasugrel are available and not contraindicated. 1, 2
• Never discontinue DAPT prematurely, especially within the first month after stent placement, as this dramatically increases risk of stent thrombosis, myocardial infarction, and death. 1, 2, 5
• Never omit PPI prescription with DAPT—this simple intervention significantly reduces gastrointestinal bleeding. 1, 2
• Never administer prasugrel to patients with prior stroke or TIA. 1, 4
• Never fail to switch from clopidogrel to ticagrelor in ACS patients when indicated. 1
• Never use aspirin doses above 100 mg daily, as higher doses increase bleeding without improving efficacy. 5

Special Populations

High Bleeding Risk (Prolonged PT/INR)

• Use clopidogrel (600 mg loading, then 75 mg daily) plus low-dose aspirin (75-100 mg daily) instead of ticagrelor or prasugrel. 5
• Investigate and correct underlying cause of coagulopathy concurrently. 5

Low Body Weight (<60 kg)

• Consider prasugrel dose reduction to 5 mg daily due to increased bleeding risk, though effectiveness of this dose has not been prospectively studied. 3