Nattokinase Does Not Clear Coronary Arteries and Is Not Recommended by Any Major Cardiovascular Guidelines
No major cardiovascular guideline from the American Heart Association, American College of Cardiology, or European Society of Cardiology recommends nattokinase for the treatment or prevention of coronary artery disease. 1
What Guidelines Actually Recommend for Coronary Artery Disease
The evidence-based, guideline-directed medical therapy for coronary artery disease includes:
Mandatory First-Line Therapies
- Aspirin 75-100 mg daily (or clopidogrel 75 mg if aspirin intolerant) 1, 2
- High-intensity statin therapy regardless of baseline cholesterol levels, with ezetimibe added if LDL goals not met 1, 2
- ACE inhibitors (or ARBs), particularly with hypertension, diabetes, heart failure, or LVEF ≤40% 1, 2
- Beta-blockers, especially in patients with prior myocardial infarction 1, 2
Additional Evidence-Based Interventions
- PCSK9 inhibitors for very high-risk patients not reaching LDL goals on statin plus ezetimibe 1, 2
- Sublingual nitroglycerin for immediate angina relief 1, 2
- Exercise-based cardiac rehabilitation as fundamental therapy 2
- Annual influenza vaccination to reduce mortality risk 2
The Evidence on Nattokinase: Why It's Not Guideline-Recommended
While some research studies suggest nattokinase may have fibrinolytic and lipid-modifying properties, the evidence has critical limitations:
Study Quality Issues
- The largest study 3 was an open-label observational study of 1,062 participants showing reduced carotid intima-media thickness and improved lipid profiles at 10,800 FU/day over 12 months
- A smaller randomized trial 4 of 178 CAD patients showed modest improvements in lipids and blood pressure when nattokinase was combined with red yeast rice over 90 days
- These studies lack the rigorous methodology, long-term follow-up, and hard clinical endpoints (mortality, myocardial infarction, stroke) required for guideline inclusion 3, 4
Critical Gaps in Evidence
- No mortality or major adverse cardiovascular event data from adequately powered randomized controlled trials 3, 4, 5
- No comparison to proven therapies like statins, which have decades of evidence showing 20-30% reductions in cardiovascular mortality 1
- Unclear safety profile with anticoagulants and antiplatelet agents, which are standard therapy in coronary disease 3, 4
Mechanism vs. Clinical Outcomes
- While nattokinase demonstrates fibrinolytic activity in vitro and reduces clotting factors in small studies 6, 7, reducing surrogate markers does not equal preventing heart attacks or death
- Proven therapies like aspirin, statins, and ACE inhibitors have demonstrated 15-40% reductions in cardiovascular mortality in large randomized trials 1
Clinical Bottom Line
For patients with coronary artery disease, prioritize guideline-directed medical therapy with proven mortality benefit: aspirin, high-intensity statin, ACE inhibitor, and beta-blocker (if prior MI). 1, 2
Nattokinase should not replace or delay initiation of evidence-based therapies. 1 If patients inquire about nattokinase, explain that while preliminary research shows some biochemical effects, it lacks the robust clinical trial evidence demonstrating reduced heart attacks, strokes, or death that established therapies possess. 3, 4, 5
Common Pitfalls to Avoid
- Do not substitute nattokinase for proven antiplatelet therapy (aspirin/clopidogrel), as this increases thrombotic risk 1
- Do not delay statin initiation in favor of "natural" alternatives, as statins reduce cardiovascular mortality by 20-30% 1
- Be cautious about bleeding risk if patients combine nattokinase with guideline-directed antiplatelet and anticoagulant therapy 3, 4
- Recognize that improved surrogate markers (lipids, carotid thickness) do not guarantee improved clinical outcomes without randomized trial evidence 3