Is it safe for a middle-aged or older adult patient with hypertension and hyperlipidemia, taking 40mg of pravastatin (pravastatin) and 10mg of Zetia (ezetimibe), to take nattokinase?

Safety of Nattokinase with Pravastatin and Ezetimibe in Hypertensive Patients

It is safe to add nattokinase to your current regimen of pravastatin 40 mg and ezetimibe 10 mg, as there are no known drug interactions between these medications, though nattokinase provides no proven cardiovascular benefit and should not be expected to improve your blood pressure or cholesterol control.

Evidence on Nattokinase Efficacy

The most rigorous evidence comes from a 3-year randomized controlled trial that directly contradicts claims about nattokinase's cardiovascular benefits:

• Nattokinase supplementation had no effect on atherosclerosis progression, blood pressure, or any cardiovascular biomarkers in a median 3-year trial of 265 individuals 1
• This trial specifically measured carotid artery intima-media thickness, arterial stiffness, blood pressure, metabolic factors, inflammatory markers, and coagulation parameters—all showed null results 1
• The study population (median age 65.3 years without clinical cardiovascular disease) closely matches your demographic profile 1

A 2023 meta-analysis presents conflicting data but with important caveats:

• Nattokinase showed modest blood pressure reductions (systolic BP decreased by 3.45 mmHg, diastolic by 2.32 mmHg) across pooled studies 2
• However, low-dose nattokinase actually increased total cholesterol and LDL cholesterol rather than improving lipid profiles 2
• The meta-analysis included only 546 participants across 6 studies, with heterogeneous dosing and shorter durations than the definitive 3-year trial 2

Your Current Evidence-Based Therapy

Your pravastatin and ezetimibe combination represents guideline-concordant therapy:

• Pravastatin 40 mg is a moderate-intensity statin that reduces LDL-C by 30-49%, appropriate for primary prevention in patients with hypertension 3
• Adding ezetimibe 10 mg to pravastatin provides incremental LDL-C reductions of 34-41% and triglyceride reductions of 21-23% 4
• This combination is well-tolerated with a safety profile similar to pravastatin monotherapy 4, 5
• The combination of low-dose pravastatin (10 mg) plus ezetimibe (10 mg) has been shown to be more effective than high-dose pravastatin (40 mg) alone for lipid control 6

Blood Pressure Management Priority

Your hypertension requires optimization according to current guidelines:

• Target systolic BP should be 120-129 mmHg for most adults with hypertension to reduce cardiovascular risk 7
• First-line antihypertensive medications include ACE inhibitors, ARBs, dihydropyridine calcium channel blockers, and thiazide/thiazide-like diuretics 7
• Combination BP-lowering treatment is recommended for most patients with confirmed hypertension (BP ≥140/90 mmHg) as initial therapy, preferably a RAS blocker with a calcium channel blocker or diuretic 7
• Fixed-dose single-pill combinations are recommended to improve adherence 7

Safety Considerations

From a drug interaction perspective:

• No treatment-related serious adverse events or drug interactions were reported with pravastatin-ezetimibe combinations in 12-month studies 5
• Nattokinase trials reported no notable adverse events related to supplementation 1, 2
• There is no pharmacological mechanism for interaction between nattokinase and statins or ezetimibe, as nattokinase is a fibrinolytic enzyme that does not affect hepatic metabolism pathways

Clinical Recommendation

Rather than adding nattokinase (which lacks proven benefit), focus on optimizing your evidence-based cardiovascular therapy:

• Ensure your blood pressure is adequately controlled with guideline-recommended antihypertensive medications 7
• Continue your pravastatin 40 mg and ezetimibe 10 mg combination, which provides proven cardiovascular risk reduction 7
• Implement lifestyle modifications including Mediterranean or DASH dietary patterns, reduced saturated fat intake, and increased physical activity 7
• Monitor LDL-C levels 4-12 weeks after any therapy changes and annually thereafter 7

If you choose to take nattokinase despite the lack of evidence, it will not cause harm through drug interactions, but it should not replace or delay optimization of your proven cardiovascular therapies.