In patients with acute coronary syndrome (including ST‑segment elevation myocardial infarction, non‑ST‑segment elevation myocardial infarction, or unstable angina), what is the recommended ticagrelor dosing, contraindications, common adverse effects, and suitable alternative antiplatelet agents?

Ticagrelor for Acute Coronary Syndrome

Ticagrelor (180 mg loading dose, then 90 mg twice daily) combined with low-dose aspirin (75–100 mg daily) is the first-line dual antiplatelet therapy for all patients with acute coronary syndrome, including STEMI, NSTEMI, and unstable angina. 1, 2

Recommended Dosing Regimen

Loading Dose

• Administer ticagrelor 180 mg orally immediately upon ACS diagnosis, before any invasive procedure. 1, 2, 3
• Platelet inhibition is achieved within approximately 30 minutes of the loading dose. 1, 4

Maintenance Dose

• Continue ticagrelor 90 mg orally twice daily for 12 months. 1, 2, 3
• The twice-daily dosing maintains consistent platelet inhibition across the dosing interval. 4, 5

Aspirin Co-Administration

• Combine ticagrelor with aspirin 75–100 mg daily (81 mg in the United States). 1, 2
• Never exceed 100 mg daily of aspirin when using ticagrelor—higher doses blunt ticagrelor's antiplatelet efficacy (FDA black-box warning). 1, 2

Standard Treatment Duration

• Maintain dual antiplatelet therapy for 12 months in all ACS patients, regardless of stent type, ACS subtype, or management strategy (PCI, medical therapy, or CABG). 1, 2, 6
• In patients with high bleeding risk (PRECISE-DAPT score ≥25), shortening to 6 months may be considered. 1, 2

Absolute Contraindications

• Active pathological bleeding (e.g., active gastrointestinal hemorrhage). 2
• History of intracranial hemorrhage. 1, 2
• Concomitant use with potent CYP3A4 inhibitors (e.g., itraconazole) during the inhibitor course and for up to two weeks after discontinuation. 2

Common Adverse Effects

Bleeding

• Ticagrelor increases non-CABG-related major bleeding compared to clopidogrel (4.5% vs 3.8%). 6
• Fatal intracranial bleeding occurs more frequently with ticagrelor than clopidogrel (0.1% vs 0.01%). 6

Dyspnea

• Dyspnea occurs in 14–39% of patients on ticagrelor versus 7–9% with clopidogrel. 2
• The symptom typically emerges within the first week, is usually mild and self-limited, and rarely necessitates discontinuation. 2, 7

Other Adverse Effects

• Ventricular pauses (mostly asymptomatic). 4, 5
• Hypotension, nausea, gout, and kidney damage have been reported. 7, 4

Bleeding Risk Mitigation Strategies

• Prescribe a proton pump inhibitor (PPI) to every patient on dual antiplatelet therapy—this is a Class I recommendation. 1, 2, 6
• Pantoprazole 40 mg daily is preferred due to minimal CYP2C19 inhibition. 2
• Use radial artery access over femoral access for PCI when performed by an experienced radial operator. 2, 6
• Maintain aspirin at 75–100 mg daily; higher doses increase bleeding without improving efficacy. 2, 6

Alternative Antiplatelet Agents

Prasugrel

• Prasugrel (60 mg loading, then 10 mg daily) is an acceptable alternative for P2Y12-inhibitor-naïve patients proceeding to PCI after coronary anatomy is defined. 1, 2, 6
• Absolute contraindication: Prior stroke or transient ischemic attack—prasugrel markedly increases cerebrovascular bleeding (Class III Harm). 1, 2
• Additional cautions: Age ≥75 years or body weight <60 kg (higher bleeding risk). 1, 2
• Do not administer prasugrel before coronary anatomy is known. 2, 6

Clopidogrel

• Clopidogrel (600 mg loading, then 75 mg daily) should be reserved only when ticagrelor and prasugrel are unavailable, not tolerated, or contraindicated. 2, 6
• Clopidogrel is preferred when oral anticoagulation is required (triple therapy) due to substantially lower bleeding risk. 2, 6
• Clopidogrel is the default choice for patients with active bleeding, very high bleeding risk, or history of intracranial hemorrhage. 2, 6

Special Clinical Scenarios

Patients with Prior Stroke or TIA

• Ticagrelor is the preferred P2Y12 inhibitor for ACS patients with prior ischemic stroke or TIA. 2
• Prasugrel is absolutely contraindicated in any patient with prior stroke/TIA, regardless of how remote the event was. 2
• If ticagrelor cannot be used, clopidogrel is the alternative. 2

Patients Requiring Oral Anticoagulation (Triple Therapy)

• Discontinue aspirin 1–4 weeks after PCI and switch from ticagrelor to clopidogrel, as clopidogrel carries substantially lower bleeding risk in triple-therapy settings. 2, 6
• Ticagrelor is not recommended as part of triple antithrombotic therapy with aspirin and oral anticoagulation. 1

Perioperative Management

• Stop ticagrelor at least 5 days before any planned surgical procedure to allow adequate recovery of platelet function. 1, 2
• Never discontinue dual antiplatelet therapy within the first 30 days after stent placement for elective non-cardiac surgery—early cessation dramatically increases stent thrombosis risk. 2, 6

Patients Previously on Clopidogrel

• Switch to ticagrelor immediately by giving the 180 mg loading dose without waiting for clopidogrel washout. 6
• The benefits of ticagrelor are observed irrespective of prior clopidogrel therapy. 1

Critical Pitfalls to Avoid

• Never discontinue dual antiplatelet therapy within the first month after stent placement—this markedly raises the risk of stent thrombosis, myocardial infarction, and death. 2, 6
• Never omit a PPI when prescribing dual antiplatelet therapy—this simple intervention significantly reduces gastrointestinal bleeding. 2, 6
• Never use aspirin doses >100 mg daily with ticagrelor—higher doses blunt ticagrelor's benefit. 2
• Never use clopidogrel as first-line therapy when ticagrelor is available and not contraindicated—this represents suboptimal care for ACS patients. 2, 6
• Never delay the ticagrelor loading dose—it should be given immediately upon ACS diagnosis, prior to any invasive procedure. 2

Superiority Over Clopidogrel

• Ticagrelor reduces cardiovascular death by 21% compared to clopidogrel in ACS patients. 6
• Ticagrelor reduces all-cause mortality (4.5% vs 5.9%, P<0.001). 6, 3
• Ticagrelor reduces myocardial infarction (5.8% vs 6.9%, P=0.005). 6
• Ticagrelor provides more consistent and potent platelet inhibition than clopidogrel because it does not require hepatic metabolic activation. 1, 3, 4