When to stop ticagrelor for ischemic and bleeding events?

When to Stop Ticagrelor for Ischemic and Bleeding Events

Pre-Surgical Discontinuation

Ticagrelor should be discontinued at least 3 days before elective surgery, with 5 days preferred for procedures with significant bleeding risk. 1, 2

• The 2017 ESC guidelines recommend discontinuation at least 3 days before surgery, though a shorter duration may be acceptable in urgent situations 1
• The 2013 ACC/AHA guidelines recommend discontinuation at least 5 days before any surgery when possible 1
• For coronary artery bypass graft surgery specifically, the protocol recommends withholding ticagrelor for 1 to 3 days, though 3-5 days is preferred to minimize bleeding risk 1
• The shorter discontinuation window compared to clopidogrel (which requires 5-7 days) is based on ticagrelor's reversible binding properties and shorter half-life of 12 hours 2

Management of Active Bleeding

When major bleeding occurs on ticagrelor, immediate discontinuation is warranted, but the decision must account for stent thrombosis risk, particularly within 2 weeks of PCI. 1

High Stent Thrombosis Risk Scenarios (Discontinuation Requires Bridging):

• Recent stent implantation (<2 weeks post-PCI) 1
• Acute coronary syndrome presentation 1
• Long stent length 1
• Proximal left anterior descending artery location 1
• Active malignancy 1

Bridging Strategy for High-Risk Patients:

For patients at very high risk of stent thrombosis who require ticagrelor discontinuation, bridging therapy with IV reversible glycoprotein inhibitors (tirofiban or eptifibatide) or cangrelor may be considered. 1

• Cangrelor is preferred due to its specific P2Y12 inhibition and quicker offset of action compared to glycoprotein inhibitors 1
• Low-molecular-weight heparins (enoxaparin) should NOT be used as bridging therapy, as they do not reduce stent thrombosis risk despite increasing bleeding risk 1
• Concomitant parenteral anticoagulation is not recommended when using glycoprotein inhibitors or cangrelor for bridging 1

Duration-Based Discontinuation Strategies

Post-ACS and PCI Standard Duration:

Ticagrelor should be continued for at least 12 months after acute coronary syndrome, regardless of stent type. 1

• In the PLATO trial, ticagrelor demonstrated superiority over clopidogrel with a 16% relative risk reduction in cardiovascular death, MI, or stroke 1
• The mortality benefit was significant (4.7% vs 6.1% in STEMI patients) 1

Early Discontinuation in Atrial Fibrillation Patients:

In patients requiring oral anticoagulation for atrial fibrillation, ticagrelor can be discontinued earlier than 12 months, transitioning to dual therapy (OAC + P2Y12 inhibitor) or monotherapy. 1

• For high ischemic/thrombotic and low bleeding risk: Continue triple therapy up to 1 month, then dual therapy up to 12 months 1
• For low ischemic/thrombotic or high bleeding risk: Discontinue aspirin at discharge, continue dual therapy (OAC + ticagrelor) up to 6 months 1
• After 6-12 months, discontinue ticagrelor and continue OAC monotherapy 1
• Clopidogrel remains the preferred P2Y12 inhibitor in this population, but ticagrelor may be considered in selected high ischemic risk patients 1

Stable CAD After Remote PCI:

In stable patients with prior PCI (>12 months) who remain at high ischemic risk and low bleeding risk, ticagrelor 60 mg twice daily plus aspirin may be considered. 1

• This strategy is supported for patients who have not had bleeding complications during initial DAPT 1
• Bleeding risk should be periodically reassessed 1

Bleeding Risk Stratification for Discontinuation Decisions

High Bleeding Risk Predictors (Consider Earlier Discontinuation):

Patients with a history of spontaneous bleeding requiring hospitalization or presence of anemia have 3-fold higher bleeding rates with ticagrelor and should be considered for earlier discontinuation or alternative strategies. 3

• History of spontaneous bleeding requiring hospitalization 3
• Presence of anemia 3
• Age ≥75 years 4
• Body weight <60 kg 1, 4
• Renal dysfunction 4
• Concomitant use of anticoagulants 1, 4

Bleeding Pattern with Ticagrelor:

• Ticagrelor increases TIMI major or minor bleeding by 2.0% absolute risk at 3 years compared to placebo 3
• Bleeding is predominantly spontaneous gastrointestinal in origin 3
• Fatal intracranial bleeds occurred more frequently with ticagrelor (0.1% vs 0.01%, P=0.02) 1
• Non-CABG major bleeding was higher with ticagrelor (4.5% vs 3.8%, P=0.03) 1

Discontinuation Due to Adverse Effects

Dyspnea-Related Discontinuation:

Dyspnea is the most common cause of premature ticagrelor discontinuation, occurring in approximately 11-12% of patients, with a 6.4-fold higher relative risk compared to clopidogrel. 5, 6

• Dyspnea is usually mild and dose-related 1
• The mechanism is likely related to ticagrelor's inhibition of adenosine reuptake by erythrocytes 1
• In real-world practice, 24% of patients discontinue ticagrelor prematurely within 1 year, with dyspnea being the leading cause (11.6%) followed by bleeding (3.7%) 6

Other Adverse Effects:

• Asymptomatic bradycardia with ventricular pauses may occur 1
• Modest increase in uric acid levels 1

Absolute Contraindications Requiring Immediate Discontinuation:

Ticagrelor must be immediately discontinued in patients with active pathological bleeding or history of intracranial hemorrhage. 7, 4

• Active bleeding is an FDA boxed warning contraindication 7, 4
• History of intracranial hemorrhage is an absolute contraindication 7, 4
• Patients with prior stroke or TIA represent a high-risk group for intracranial bleeding when receiving DAPT 7

Critical Pitfalls to Avoid:

• Never use aspirin >100 mg daily with ticagrelor, as higher doses paradoxically decrease ticagrelor's effectiveness and increase bleeding risk 7, 4
• Do not use low-molecular-weight heparin as bridging therapy when discontinuing ticagrelor for surgery in high stent thrombosis risk patients 1
• Do not avoid ticagrelor solely because the patient is on heparin during acute coronary syndrome management—this combination is guideline-recommended 4
• Do not perform angioplasty and stenting as initial treatment in patients with severe intracranial stenosis (70-99%), even for those already on antithrombotic therapy (Class 3: Harm) 7

Resumption After Discontinuation:

Antiplatelet therapy should be resumed within 24 hours after procedures if there are no bleeding complications. 2

• For patients who undergo PCI, ticagrelor should be restarted as soon as possible 2
• After major bleeding resolves, the decision to restart should weigh ongoing ischemic risk against recurrent bleeding risk 1