What is the role of heparin (unfractionated heparin (UFH) or low molecular weight heparin (LMWH)) in cardiac disease?

Role of Heparin in Cardiac Disease

Heparin (both unfractionated and low molecular weight) is indicated and effective for multiple cardiac conditions including acute coronary syndromes, prevention of thromboembolism in atrial fibrillation, and prophylaxis during cardiac procedures, though low molecular weight heparins offer practical advantages with at least equivalent efficacy to unfractionated heparin in most settings. 1, 2

Mechanism and Pharmacology

Heparin works by enhancing antithrombin III activity, which inhibits activated coagulation factors, particularly Factor Xa and Factor IIa (thrombin), thereby preventing clot formation but not lysing existing clots 2. The drug achieves immediate peak plasma concentration after intravenous administration with a dose-dependent half-life ranging from 0.5 to 2 hours 2.

Primary Cardiac Indications

Acute Coronary Syndromes (Unstable Angina/Non-ST Elevation MI)

For unstable angina and non-Q-wave MI, unfractionated heparin combined with aspirin is recommended as standard therapy, though the evidence shows only modest additional benefit over aspirin alone. 1

• Unfractionated heparin reduces the combined endpoint of refractory angina, MI, and death compared to placebo (risk reduction 0.29), though aspirin alone shows greater risk reduction (0.56) 1
• Meta-analysis of heparin added to aspirin showed risk reduction of 0.67 (95% CI: 0.44-1.02), which does not provide conclusive evidence of benefit, but guidelines pragmatically recommend the combination 1
• Recommended dosing: 5000 U IV bolus followed by 32,000 U per 24 hours by continuous IV infusion, adjusted to maintain aPTT at 1.5-2.0 times control 1
• A critical limitation is the rebound phenomenon—initial event reduction is lost after heparin discontinuation, with no sustained protective effect 1

Low Molecular Weight Heparin Superiority in ACS

Low molecular weight heparins, particularly enoxaparin, demonstrate superior efficacy compared to unfractionated heparin in acute coronary syndromes with significant practical advantages. 1

• Enoxaparin reduced the primary endpoint (death/MI/recurrent angina) from 19.6% to 16.6% at 14 days (OR 0.80,95% CI: 0.67-0.98) in the ESSENCE trial, with sustained benefit at 1 year 1
• Dalteparin showed highly significant reduction in death or new MI at 6 days (1.8% vs 4.8%, risk ratio 0.37) in the FRISC trial 1, 3
• LMWH advantages: Enhanced anti-Xa activity, more predictable anticoagulant effect, subcutaneous weight-adjusted dosing without laboratory monitoring, and lower rates of thrombocytopenia 1
• Meta-analysis confirms LMWH is at least as effective as unfractionated heparin acutely, with enoxaparin showing superiority in head-to-head comparisons 1

Post-Myocardial Infarction with Thrombolytic Therapy

• After thrombolytic therapy for acute MI: 5000 U IV bolus followed by 24,000 U per 24 hours adjusted to maintain therapeutic aPTT 1
• Important caveat: The role of heparin post-thrombolysis remains unproven, and when combined with thrombolytic agents or GP IIb/IIIa antagonists, full-dose heparin increases bleeding risk, necessitating dose reduction 1

Venous Thromboembolism Prevention and Treatment

Prophylaxis in Cardiac Surgery

• For DVT/PE prophylaxis: 5000 U subcutaneously every 8-12 hours 1, 2
• In high-risk patients (major abdominothoracic surgery): Adjusted low-dose heparin to prolong aPTT by 4-5 seconds into upper normal range 4

Active Thromboembolism Treatment

• Treatment of DVT: 5000 U IV bolus followed by 32,000 U per 24 hours by IV infusion, adjusted to maintain aPTT in therapeutic range (1.5-2.5 times control) 1, 4
• LMWH for VTE: Meta-analysis of 11 studies (>3500 patients) showed LMWH had less major bleeding (OR 0.57, P=0.05) and lower mortality (OR 0.71, P=0.02) compared to unfractionated heparin 1

Atrial Fibrillation Management

For patients with atrial fibrillation requiring temporary interruption of oral anticoagulation, bridging with heparin depends on thromboembolic risk stratification. 1

• In patients without mechanical valves, anticoagulation may be interrupted for up to 1 week for surgical procedures without substituting heparin 1
• In high-risk patients (prior stroke/TIA/systemic embolism) or those with mechanical prosthetic valves, unfractionated or low molecular weight heparin bridging is indicated 1
• LMWH advantages for bridging: Longer half-life, >90% bioavailability after subcutaneous injection, predictable clearance enabling once or twice-daily dosing without monitoring, and lower risk of heparin-induced thrombocytopenia 1

Perioperative Management

Timing of Discontinuation

• Unfractionated heparin: Stop IV infusion at least 4-6 hours before surgery to eliminate residual anticoagulant effect 5
• LMWH: Administer last pre-operative dose approximately 24 hours before surgery rather than 10-12 hours before, as studies show 34% of patients had therapeutic levels at surgery when dosed 12 hours pre-operatively 5

Postoperative Resumption

• Resume unfractionated heparin ≥24 hours after surgery rather than within 24 hours to reduce bleeding risk 5, 6
• When restarting postoperatively, avoid bolus dosing and begin with lower-intensity infusion with lower target aPTT than used for full-dose initiation 5, 6
• For high-risk patients (e.g., mechanical mitral valves), maintain heparin until INR reaches therapeutic range with warfarin (2.5-3.5 for mechanical mitral valves) 6

Critical Monitoring Parameters

• Therapeutic aPTT target: 1.5-2.5 times control value (mean of laboratory's normal range) 1, 4
• Geriatric consideration: Patients over 60 years may have higher plasma heparin levels and longer aPTTs at similar doses 2
• Bleeding time is usually unaffected by heparin, but various clotting times (aPTT, PT, whole blood clotting time) are prolonged by therapeutic doses 2

Common Pitfalls and Caveats

• Rebound thrombosis: Initial benefits of heparin are lost after discontinuation, particularly problematic in unstable angina 1
• Unpredictable anticoagulation with UFH: Heparin binding to plasma proteins (amplified by acute phase response) makes therapeutic control difficult 1
• Limited effectiveness: Heparin has reduced activity against platelet-rich and clot-bound thrombin 1
• Bleeding risk with combination therapy: When combined with thrombolytics or GP IIb/IIIa antagonists, full-dose heparin significantly increases bleeding complications 1
• Long-term LMWH concerns: Prolonged outpatient LMWH treatment beyond the acute phase shows less convincing evidence, with meta-analysis demonstrating increased major bleeding risk (OR 2.26,95% CI: 1.63-3.41) 1

Practical Algorithm for Heparin Selection

For acute coronary syndromes without planned early invasive procedure:

• Initiate LMWH (enoxaparin preferred based on superior outcomes) with aspirin 1
• Continue for 2-8 days during acute phase 1

For acute coronary syndromes with planned early catheterization/PCI:

• LMWH can be continued as "bridge-to-revascularization" until intervention 7

For perioperative bridging in high-risk patients:

• Stop warfarin 5 days before surgery 5
• Begin LMWH 1-2 days after warfarin interruption 5
• Give last LMWH dose 24 hours before surgery 5
• Resume ≥24 hours postoperatively without bolus, using lower-intensity infusion 5, 6

For venous thromboembolism treatment:

• LMWH is preferred over unfractionated heparin due to superior safety profile and equivalent efficacy 1