Do you start a heparin (unfractionated heparin) drip in a patient with Non-ST-Elevation Myocardial Infarction (NSTEMI) and an elevated International Normalized Ratio (INR) of 4.0?

Anticoagulation Management in NSTEMI with INR 4.0

Do not start a heparin drip in a patient with NSTEMI and an INR of 4.0; instead, hold additional anticoagulant therapy until the INR decreases to less than 2.0, while initiating antiplatelet therapy immediately. 1

Immediate Management Strategy

Withhold Additional Anticoagulation

• The American College of Cardiology recommends holding anticoagulant therapy (including heparin) until INR falls below 2.0 to avoid unacceptably high bleeding risk. 1
• An INR of 4.0 represents supratherapeutic anticoagulation that significantly increases hemorrhagic complications when combined with additional anticoagulants 2, 1

Initiate Antiplatelet Therapy Despite Elevated INR

• Start aspirin and a P2Y12 inhibitor (clopidogrel) immediately, even with therapeutic warfarin anticoagulation, particularly if an invasive strategy with anticipated stent implantation is planned. 2, 1
• The American Heart Association emphasizes that antiplatelet therapy should not be delayed in NSTEMI patients who are therapeutically anticoagulated with warfarin 2, 1

Consider Warfarin Reversal

• For supratherapeutic INR (4.0), urgent surgical needs, or unacceptably high bleeding risk, consider warfarin reversal with vitamin K or fresh-frozen plasma based on clinical judgment 2, 1
• For INR 5.0-9.0 without bleeding, omit the next 1-2 doses of warfarin and give oral vitamin K₁ 1-2.5 mg if the patient has bleeding risk factors 3
• Oral vitamin K₁ 1 mg reduces INR to <4 in 85% of patients within 24 hours 3

Timing of Heparin Initiation

When to Start Anticoagulation

• Begin heparin therapy once INR decreases to <2.0 1
• Monitor INR closely (every 3-4 days initially) during the transition period 3
• The general guideline is not to initiate anticoagulant therapy until the INR is less than 2.0 2

Choice of Anticoagulant

• Unfractionated heparin remains the most commonly used anticoagulant in NSTEMI patients (42% in contemporary practice) 4
• Bivalirudin may be preferred in patients at higher baseline bleeding risk, as it demonstrates lower bleeding rates compared to heparin with glycoprotein IIb/IIIa inhibitors 5
• Low molecular weight heparin is used in 27% of NSTEMI patients and may be considered as an alternative 4

Triple Antithrombotic Therapy Considerations

If Warfarin Indication Exists

• Once INR normalizes to <2.0 and heparin is initiated for acute management, plan for eventual triple therapy (warfarin + aspirin + P2Y12 inhibitor) if the patient has an established indication for warfarin (atrial fibrillation, left ventricular thrombus, mechanical prosthetic valve) 1
• Target INR 2.0-2.5 (not 2.0-3.0) during triple therapy, especially in older patients and those with bleeding risk factors 2, 1
• Use low-dose aspirin 75-81 mg daily to minimize bleeding risk 2, 1

Duration Strategy

• Triple therapy should be used for the minimum time necessary (typically 1 week to 1 month for very high bleeding risk, maximum 6 months for most patients) 1, 6
• After completing triple therapy, transition to dual therapy with warfarin plus either aspirin or clopidogrel for an additional 6 months 1
• Mandatory proton pump inhibitor therapy during triple therapy to reduce gastrointestinal bleeding 1

Critical Pitfalls to Avoid

Bleeding Risk with Elevated INR

• Major and minor bleeding rates with combination warfarin-aspirin therapy are 2% and 15% respectively 2
• The combination of heparin with supratherapeutic INR creates an unacceptably high bleeding risk that outweighs potential benefits 2, 1
• There is a 5-fold difference in bleeding rates between lowest and highest CRUSADE bleeding risk groups 4

Reversal Precautions

• Avoid high-dose vitamin K (>5 mg) in patients with high thromboembolic risk, as it causes prolonged warfarin resistance 3
• Avoid subcutaneous vitamin K, as absorption is unpredictable and delayed 3
• Reserve IV vitamin K for life-threatening bleeding only due to risk of anaphylaxis 3

Restarting Warfarin After Acute Phase

• Restart warfarin immediately at 50-75% of the previous maintenance dose once INR normalizes and acute phase management is complete 3
• Do not use loading doses when restarting warfarin, as this increases hemorrhagic risk without faster protection 3
• Monitor INR strictly between 2.0-2.5 (not 2.0-3.0) with more frequent checks during triple therapy 1