What are the indications, preferred agents, and recommended duration of dual antiplatelet therapy in adults with coronary artery disease after acute coronary syndrome or percutaneous coronary intervention (including stent type and bleeding risk)?

Dual Antiplatelet Therapy in Coronary Artery Disease

All patients with acute coronary syndrome (ACS) and all patients undergoing percutaneous coronary intervention (PCI) with stent placement must receive dual antiplatelet therapy (DAPT) combining aspirin 75–100 mg daily with a P2Y12 inhibitor for 12 months, unless high bleeding risk mandates shortening to 6 months. 1, 2, 3

P2Y12 Inhibitor Selection Algorithm

First-Line Agent: Ticagrelor

• Ticagrelor (180 mg loading dose, then 90 mg twice daily) is the preferred P2Y12 inhibitor for all ACS patients, regardless of whether they undergo PCI, medical management, or CABG. 1, 2, 3
• Ticagrelor reduces cardiovascular death by an absolute 1.4% compared with clopidogrel (4.5% vs 5.9%, P<0.001) and lowers all-cause mortality, myocardial infarction, and stent thrombosis. 2
• Administer the loading dose immediately upon ACS diagnosis, before any invasive procedure. 2

Second-Line Agent: Prasugrel

• Prasugrel (60 mg loading dose, then 10 mg daily) is acceptable for P2Y12-naïve patients proceeding to PCI, but only after coronary anatomy is defined. 1, 2, 3
• Absolute contraindication: Prior stroke or TIA at any time—prasugrel increases cerebrovascular bleeding and worsens net clinical outcomes (Class III Harm). 1, 2, 4
• Relative contraindications: Age ≥75 years or body weight <60 kg (consider 5 mg daily maintenance dose). 2, 4
• Do not administer prasugrel before angiography confirms PCI will be performed. 1, 2

Third-Line Agent: Clopidogrel

• Clopidogrel (600 mg loading dose, then 75 mg daily) is reserved only when ticagrelor and prasugrel are unavailable, not tolerated, or contraindicated. 1, 2, 3
• Mandatory scenarios for clopidogrel:
  • Requirement for oral anticoagulation (triple therapy)—clopidogrel has substantially lower bleeding risk than ticagrelor or prasugrel. 2, 4
  • History of intracranial hemorrhage. 2
  • Active bleeding or very high bleeding risk. 2

Duration of DAPT by Clinical Scenario

Acute Coronary Syndrome (STEMI, NSTEMI, Unstable Angina)

• Standard duration: 12 months for all ACS patients, irrespective of stent type, ACS subtype, or management strategy (PCI, medical therapy, or CABG). 1, 2
• High bleeding risk (PRECISE-DAPT score ≥25): Shorten to 6 months. 1
• Extended duration (>12 months): May be considered in patients who tolerate DAPT without bleeding and have high ischemic risk. 1

Stable Ischemic Heart Disease (SIHD) After PCI

• Drug-eluting stent (DES): 6 months of DAPT. 1
• Bare-metal stent (BMS): 1 month of DAPT. 1
• High bleeding risk: 1–3 months of DAPT with subsequent transition to P2Y12 inhibitor monotherapy is reasonable. 1

Post-CABG

• Resume the P2Y12 inhibitor as soon as possible after surgery to complete the 12-month DAPT course. 1, 2
• Discontinue ticagrelor or clopidogrel ≥5 days before elective CABG; discontinue prasugrel ≥7 days before. 1, 2

Bleeding Risk Mitigation Strategies (Class I Recommendations)

Mandatory Interventions

• Prescribe a proton pump inhibitor (PPI) to every patient on DAPT—this markedly reduces gastrointestinal bleeding. 1, 2, 3
• Pantoprazole 40 mg daily is preferred because it has the lowest propensity for CYP2C19 inhibition and does not attenuate clopidogrel's antiplatelet activity. 2

Aspirin Dosing

• Maintain aspirin at 75–100 mg daily (81 mg in the United States)—never exceed 100 mg when combined with any P2Y12 inhibitor. 1, 2, 3
• Higher aspirin doses blunt ticagrelor's antiplatelet effect (FDA black-box warning) and increase bleeding without added benefit. 2

Vascular Access

• Use radial artery access over femoral access for PCI when performed by an experienced radial operator—this reduces bleeding and vascular complications. 1, 2, 3

Special Clinical Scenarios

Triple Therapy (DAPT + Oral Anticoagulation)

• Discontinue aspirin 1–4 weeks after PCI and switch the P2Y12 inhibitor from ticagrelor/prasugrel to clopidogrel—clopidogrel carries substantially lower bleeding risk in triple-therapy settings. 2, 4
• Limit triple therapy duration to a maximum of 6 months or omit after hospital discharge, balancing ischemic and bleeding risks. 1

Perioperative Management

• Do not discontinue DAPT within the first 30 days after stent placement for elective non-cardiac surgery—early cessation dramatically increases stent thrombosis, myocardial infarction, and death risk. 1, 2, 5
• If surgery cannot be delayed beyond 30 days, proceed with continued DAPT. 5
• After 30 days, stop the P2Y12 inhibitor for platelet function recovery (clopidogrel 5–7 days, prasugrel 7–10 days, ticagrelor 3–5 days) while continuing aspirin. 5

Transition to P2Y12 Inhibitor Monotherapy

• In selected patients who have tolerated DAPT without bleeding, discontinue aspirin after 1–3 months and continue P2Y12 inhibitor monotherapy—this reduces bleeding while preserving ischemic protection. 1, 2

Patients with Prior Stroke/TIA

• Ticagrelor is the preferred P2Y12 inhibitor; prasugrel is absolutely contraindicated regardless of how remote the stroke/TIA was. 2, 4
• Clopidogrel is the alternative if ticagrelor is unavailable or not tolerated. 2

Critical Pitfalls to Avoid

• Never discontinue DAPT within the first month after stent placement—80% of stent thrombosis events occur within the first 30 days, with a hazard ratio of ~161 for catastrophic events. 2, 4
• Never omit a PPI when prescribing DAPT—this simple intervention significantly reduces gastrointestinal bleeding. 1, 2, 3
• Never use clopidogrel as first-line therapy when ticagrelor is available and not contraindicated—this represents suboptimal care for ACS patients. 2, 4
• Never administer prasugrel to patients with prior stroke/TIA—this is an absolute contraindication with no temporal exemption. 1, 2, 4
• Never exceed 100 mg daily aspirin dose with ticagrelor—higher doses diminish ticagrelor's efficacy. 2
• Never administer prasugrel before coronary anatomy is known—wait for angiographic confirmation of PCI. 1, 2