Best Non-Statin for Women Over 50
Ezetimibe 10 mg daily is the best first-line non-statin lipid-lowering therapy for women over 50 with hyperlipidemia. 1
Primary Recommendation: Ezetimibe
Start with ezetimibe 10 mg daily as the initial non-statin therapy, which reduces LDL-C by approximately 15-20% as monotherapy. 1 The American College of Cardiology prioritizes ezetimibe because it has demonstrated cardiovascular outcomes benefit in the IMPROVE-IT trial and has an excellent safety profile comparable to placebo. 2, 1
Why Ezetimibe First
- Proven cardiovascular benefit: Ezetimibe is the only non-statin with demonstrated reduction in cardiovascular events when added to therapy in post-ACS patients. 1
- Excellent tolerability: Common adverse effects are mild, including upper respiratory tract infection (4.3%), diarrhea (4.1%), and arthralgia (3.0%). 3
- No significant drug interactions: Works by inhibiting cholesterol absorption in the small intestine without affecting fat-soluble vitamins or bile acids. 1
- Simple dosing: Once daily, can be taken any time of day. 3
Sequential Add-On Therapy Algorithm
Step 1: Ezetimibe Monotherapy
- Start ezetimibe 10 mg daily. 1
- Reassess LDL-C at 4 weeks. 3
- If LDL-C target not achieved, proceed to Step 2. 1
Step 2: Add Bempedoic Acid
- Add bempedoic acid 180 mg daily to ezetimibe, providing an additional 15-25% LDL-C reduction. 1
- Bempedoic acid works upstream from statins in the liver with low rates of muscle-related adverse effects. 1
- Monitor for hyperuricemia and tendon disorders. 4
Step 3: Consider PCSK9 Inhibitors
- Reserve for very high-risk women with persistent LDL-C elevation despite ezetimibe plus bempedoic acid. 1
- PCSK9 inhibitors (alirocumab or evolocumab) reduce LDL-C by 50-60%. 4, 1
- Subcutaneous administration required every 2-4 weeks. 4
Alternative Option: Bile Acid Sequestrants
Consider colesevelam only as a second-line alternative if ezetimibe is not tolerated or if the patient has concurrent type 2 diabetes. 4
When to Use Colesevelam
- Patient has type 2 diabetes requiring both LDL-C lowering and glycemic control (colesevelam lowers HbA1c by ~0.5%). 4, 5
- Triglycerides are <300 mg/dL (contraindicated if TG >500 mg/dL). 4
- Patient cannot tolerate ezetimibe or bempedoic acid. 1
Colesevelam Dosing and Effects
- Dose: 6 tablets (3.75 g) orally once daily or 3 tablets twice daily with meals. 4
- LDL-C reduction: 15% as monotherapy. 4
- Additional 10-16% reduction when combined with low-to-moderate intensity statins. 4
Important Colesevelam Limitations
- Gastrointestinal side effects: Constipation is the most common adverse effect. 4, 5
- Drug interactions: Take other medications at least 4 hours before or after colesevelam to avoid impaired absorption. 4
- May increase triglycerides: Monitor TG levels and discontinue if signs of pancreatitis occur. 4
- Bulky formulation: 6 tablets daily or powder packets may reduce adherence. 4
Risk-Based LDL-C Targets for Women Over 50
Very High-Risk Women
- Target: LDL-C <55 mg/dL with ≥50% reduction from baseline. 1
- Start ezetimibe 10 mg daily, add bempedoic acid 180 mg daily if not at goal. 1
High-Risk Women
- Target: LDL-C <70 mg/dL. 4, 1
- Start ezetimibe 10 mg daily, add bempedoic acid 180 mg daily if not at goal. 1
Moderate-Risk Women
Common Pitfalls to Avoid
- Don't start with bile acid sequestrants: Ezetimibe has superior tolerability, simpler dosing, and proven cardiovascular outcomes benefit. 2, 1
- Don't jump to PCSK9 inhibitors: Follow the stepwise approach (ezetimibe → bempedoic acid → PCSK9 inhibitor) unless dealing with extremely high-risk patients. 1
- Don't use colesevelam if triglycerides are elevated: Bile acid sequestrants can worsen hypertriglyceridemia and cause pancreatitis. 4
- Don't forget drug-drug interactions with colesevelam: Separate dosing by at least 4 hours from other medications. 4