Heparin in Unstable Angina
Yes, heparin is indicated in unstable angina and should always be administered in combination with aspirin unless contraindications exist. 1, 2
Core Recommendation
Heparin combined with aspirin reduces cardiovascular death and myocardial infarction by approximately 30% compared to aspirin alone in patients with unstable angina. 1, 3 This represents a reduction in MI rates from 11.9% with placebo to 1.6% with the combination therapy (P=0.001). 3
Evidence Supporting Combined Therapy
The American Heart Association explicitly states that heparin is always used in combination with aspirin in patients with acute myocardial ischemia, including those with unstable angina. 1, 2, 3 This is not optional—it is standard of care.
When heparin is given alone:
- Reduces MI incidence from 11.9% to 0.8% (P<0.0001) 1
- Reduces refractory angina from 22.9% to 8.5% (P=0.002) 1, 3
Meta-analysis of 6 randomized trials showed the combination reduced death or MI from 10.3% to 7.9% (absolute risk reduction 2.4%, OR 0.74). 1, 3
Specific Dosing Protocol
Initial bolus: 60-70 units/kg IV (maximum 5,000 units) 2
Continuous infusion: 12-15 units/kg/hour 2
Target aPTT: 1.5-2.0 times control (or 50-70 seconds absolute) 1, 2, 3
Alternative dosing from landmark trials: 5,000 U IV bolus followed by 1,000 U/hour infusion, adjusted to maintain therapeutic aPTT. 1
Treatment duration: Approximately 5-6 days 1
Critical Timing Considerations
Initiate heparin within 24 hours of symptom onset. 1 Treatment decisions should be based on ECG findings and clinical presentation, not delayed pending troponin results. 2
High-risk features mandating immediate anticoagulation include: 1, 2
- ST-segment depression on ECG
- Recurrent chest pain despite initial therapy
- Hemodynamic instability
- Major arrhythmias
Important Caveats and Pitfalls
Rebound Phenomenon
Critical warning: Discontinuing heparin without aspirin coverage causes reactivation of unstable angina in 13% of patients (14/107) within 9.5 ± 5 hours. 4 This rebound required urgent intervention (thrombolysis, angioplasty, or CABG) in 11 patients. 4 Always ensure aspirin is continued when stopping heparin to prevent this withdrawal phenomenon. 4
Bleeding Risk
The combination increases major bleeding by approximately 3 additional events per 1,000 patients compared to aspirin alone. 3 However, the mortality and MI reduction benefits outweigh bleeding risk in unstable angina. 3
Monitoring Requirements
Check aPTT every 4-6 hours during initiation, then daily once stable. 5 Weight-based dosing nomograms improve outcomes compared to fixed-dose regimens. 5
Low-Molecular-Weight Heparin Alternative
Enoxaparin may be used as an alternative to unfractionated heparin, with evidence suggesting potential superiority. 1, 2 The ESSENCE trial showed enoxaparin reduced death, MI, and recurrent angina by 16% compared to standard heparin. 6 LMWH offers practical advantages: subcutaneous administration, no monitoring required, and more predictable anticoagulation. 1, 6, 7
When Combined with Other Therapies
If using GP IIb/IIIa inhibitors or thrombolytics, reduce heparin dose to mitigate bleeding risk. 1, 5 The American Heart Association advises dose reduction with maximum caps in these settings. 5
Contraindications to Consider
Do not use heparin in patients with:
- Active bleeding or hemorrhagic diathesis 1
- Heparin-induced thrombocytopenia (consider direct thrombin inhibitors instead) 1
- Severe uncontrolled hypertension
The combination of aspirin plus heparin is evidence-based standard of care—do not withhold aspirin in patients on heparin drips for acute coronary syndromes despite increased bleeding risk. 3