After percutaneous coronary intervention, should I prescribe ticagrelor or clopidogrel, and what are the appropriate loading and maintenance doses and contraindications?

Ticagrelor vs Clopidogrel After PCI

For acute coronary syndrome (ACS) patients undergoing PCI, prescribe ticagrelor (180 mg loading dose, then 90 mg twice daily) over clopidogrel as first-line therapy, combined with low-dose aspirin 75-100 mg daily for 12 months. 1, 2

First-Line P2Y12 Inhibitor Selection

Ticagrelor is the preferred P2Y12 inhibitor for all ACS patients after PCI because it reduces major adverse cardiovascular events, stent thrombosis, and all-cause mortality compared with clopidogrel. 1, 2

• Loading dose: Administer ticagrelor 180 mg orally immediately when ACS is diagnosed, before any invasive procedure. 1, 2
• Maintenance dose: Continue ticagrelor 90 mg twice daily for 12 months. 1, 2
• Aspirin dose: Combine with low-dose aspirin 75-100 mg daily (never exceed 100 mg, as higher doses diminish ticagrelor's efficacy). 1, 2

The 2019 ESC/EACTS guidelines explicitly state that ticagrelor or prasugrel should be used over clopidogrel for ACS patients undergoing PCI (Class I recommendation). 1 This recommendation is based on superior efficacy in reducing ischemic events without prohibitive bleeding risk in the general ACS population.

When to Use Clopidogrel Instead

Clopidogrel (600 mg loading dose, then 75 mg daily) should be reserved for specific situations where ticagrelor is contraindicated or not tolerated: 1

• Patients requiring oral anticoagulation (triple therapy): Clopidogrel has substantially lower bleeding risk than ticagrelor when combined with anticoagulation. 1, 2
• History of intracranial hemorrhage: Ticagrelor is contraindicated in this population. 2
• Active bleeding or very high bleeding risk: Clopidogrel provides less potent platelet inhibition with lower bleeding rates. 1
• Ticagrelor intolerance: Most commonly due to dyspnea (occurs in 10-15% of patients). 3
• Cost concerns: When ticagrelor is financially prohibitive and patient cannot afford therapy. 3

The 2018 North American consensus on atrial fibrillation patients undergoing PCI explicitly states that clopidogrel is the P2Y12 inhibitor of choice when oral anticoagulation is required, due to lower bleeding risk. 1

Alternative: Prasugrel

Prasugrel (60 mg loading dose, then 10 mg daily) is an acceptable alternative to ticagrelor for P2Y12-inhibitor naïve patients with known coronary anatomy proceeding to PCI. 1

Absolute contraindication: Never use prasugrel in patients with prior stroke or TIA—it increases cerebrovascular bleeding and worsens outcomes (Class III Harm recommendation). 1, 2

Relative contraindications: Age ≥75 years or body weight <60 kg (higher bleeding risk). 1

Standard Duration of Therapy

Continue dual antiplatelet therapy (DAPT) for 12 months in all ACS patients after PCI, regardless of stent type or ACS subtype. 1, 2

• High bleeding risk patients (PRECISE-DAPT score ≥25): Consider shortening DAPT to 6 months. 1
• Low bleeding risk, high ischemic risk patients: May extend beyond 12 months with ticagrelor 60 mg twice daily. 2

Bleeding Risk Mitigation Strategies

Every patient on DAPT must receive these protective measures: 1, 2

• Prescribe a proton pump inhibitor (PPI): This is a Class I recommendation to reduce gastrointestinal bleeding. 1, 2
• Use radial artery access for PCI when performed by an experienced radial operator. 1
• Maintain aspirin at 75-100 mg daily: Higher doses increase bleeding without improving efficacy. 1, 2

Special Clinical Scenarios

Patients Already on Clopidogrel

Switch to ticagrelor immediately by administering the 180 mg loading dose without waiting for clopidogrel washout. 4 The ESC guidelines explicitly recommend this transition for ACS patients regardless of prior clopidogrel timing or loading dose. 4

Patients with Prior Stroke or TIA

Use ticagrelor, not prasugrel. 2 Ticagrelor is contraindicated only in patients with prior intracranial hemorrhage, whereas prasugrel is contraindicated in all patients with any prior stroke or TIA. 1, 2

Elderly Patients (≥70 Years)

The POPular AGE trial (2020) found that in patients ≥70 years with NSTE-ACS, clopidogrel resulted in 24% fewer bleeding events compared to ticagrelor (18% vs 24%, HR 0.71, p=0.02) without increasing ischemic events. 5 However, current guidelines still recommend ticagrelor as first-line therapy, with clopidogrel reserved for those at particularly high bleeding risk. 1

Patients Requiring CABG

Resume P2Y12 inhibitor therapy postoperatively as soon as deemed safe to complete 12 months of DAPT. 1 Continue aspirin perioperatively if bleeding risk allows. 1

Critical Pitfalls to Avoid

• Never discontinue DAPT within the first month after stent placement—this dramatically increases stent thrombosis, myocardial infarction, and death risk. 2, 4
• Never omit a PPI when prescribing DAPT—this simple intervention significantly reduces gastrointestinal bleeding. 1, 2
• Never use aspirin >100 mg daily with ticagrelor—higher doses blunt ticagrelor's antiplatelet effect. 2
• Never give prasugrel to patients with prior stroke/TIA—this is an absolute contraindication. 1, 2
• Never use clopidogrel as first-line therapy when ticagrelor is available and not contraindicated—this represents suboptimal care for ACS patients. 1, 2

Practical Implementation Algorithm

1. Confirm ACS diagnosis → Immediately load with ticagrelor 180 mg + aspirin 150-300 mg. 1, 2
2. Check for ticagrelor contraindications:
   • Prior intracranial hemorrhage? → Use clopidogrel. 2
   • Requires oral anticoagulation? → Use clopidogrel. 1, 2
   • Active bleeding or very high bleeding risk? → Use clopidogrel. 1
3. If considering prasugrel instead:
   • Prior stroke/TIA? → Never use prasugrel; use ticagrelor. 1, 2
   • Age ≥75 or weight <60 kg? → Prefer ticagrelor. 1
4. Maintenance therapy: Ticagrelor 90 mg twice daily + aspirin 75-100 mg daily + PPI for 12 months. 1, 2