Management of Triple Antithrombotic Therapy in NSTEMI Patients on Oral Anticoagulation

Initial Antithrombotic Strategy

The American College of Cardiology recommends triple antithrombotic therapy consisting of a vitamin K antagonist (or other oral anticoagulant), aspirin, and a P2Y12 receptor inhibitor for patients with NSTEMI who are already on oral anticoagulation 1, 2
The duration of triple therapy should be minimized to limit the risk of bleeding, which can increase from 4-6% with dual therapy to 10-14% with triple therapy 1
Aspirin should be continued indefinitely with a maintenance dose of 81 mg daily in patients treated with ticagrelor and 81-325 mg daily in all other patients 4, 5

For patients requiring triple therapy, clopidogrel is the preferred P2Y12 inhibitor over prasugrel or ticagrelor due to lower bleeding risk 6
In patients undergoing PCI who are not at high risk for bleeding complications, prasugrel may be reasonable to choose over clopidogrel 4, 5
Ticagrelor is reasonable to use in preference to clopidogrel for patients undergoing an early invasive or ischemia-guided strategy, but this must be balanced against the increased bleeding risk in triple therapy 4, 7

If the risk of morbidity from bleeding outweighs the anticipated benefit of a recommended duration of P2Y12 inhibitor therapy after stent implantation, earlier discontinuation (<12 months) of P2Y12 inhibitor therapy is reasonable 1, 4

Proton pump inhibitors should be prescribed in patients with NSTEMI with a history of gastrointestinal bleeding who require triple antithrombotic therapy 1, 2, 8
Proton pump inhibitor use is reasonable even in patients without a known history of gastrointestinal bleeding who require triple antithrombotic therapy 1, 2
Targeting oral anticoagulant therapy to a lower international normalized ratio (INR) (e.g., 2.0 to 2.5) may be reasonable in patients with NSTEMI managed with aspirin and a P2Y12 inhibitor 1, 4

For elderly patients (≥80 years old), the bleeding risk with triple antithrombotic therapy is substantially higher, requiring even more careful consideration of the necessity and duration of triple therapy 9
In patients with high bleeding risk, consider shortening the duration of triple therapy to the absolute minimum necessary (even as short as during the hospital stay) 1, 8
The HAS-BLED score should be used to assess bleeding risk and guide therapy decisions in patients requiring triple therapy 1

Avoid prolonged triple therapy beyond what is absolutely necessary, as bleeding risk increases substantially with duration 1, 2
Don't use prasugrel as part of triple therapy in patients at high risk for bleeding (history of stroke, age ≥75 years, weight <60 kg) 4
Don't forget to initiate a proton pump inhibitor for gastroprotection in all patients on triple therapy 1, 8
Avoid higher maintenance doses of aspirin (>81 mg) when possible in patients on triple therapy to reduce bleeding risk 4