Opinion
Video
Effective Approaches for Utilizing Nonstatin Therapies
Author(s):
Panelists discuss how medical professionals navigate statin initiation, considering contraindications or delays in specific patient populations, including those with liver disease or renal impairment, older adults, and other high-risk groups, while also examining evolving treatment patterns and factors influencing the adoption of more intensive low-density lipoprotein cholesterol (LDL-C)–lowering therapies.
Management of LDL-C–Lowering in Statin-Intolerant Patients Postcardiac Event
Overview
Statin intolerance presents a significant challenge in managing patients’ postcardiac event, where aggressive LDL-C level reduction is essential for secondary prevention. This summary outlines evidence-based approaches for managing these high-risk patients.
Recommended LDL-C–Lowering Strategies
Initial Approach
- Confirm true statin intolerance through rechallenge with different statin formulations, lower doses, or alternate-day dosing
- Target the lowest possible LDL-C level in postcardiac event patients, with goals typically less than 55 mg/dL or at least a 50% reduction from baseline
Nonstatin Therapies
First-Line Nonstatin Option
- Ezetimibe: Recommended as initial nonstatin therapy
- Provides 15% to 25% additional LDL-C level reduction
- Well-tolerated with minimal adverse effects
- Demonstrated cardiovascular benefit in IMPROVE-IT trial
- Cost-effective compared with newer agents
Second-Line Options
- PCSK9 inhibitors (e.g., evolocumab and alirocumab)
- Very effective (50%-60% additional LDL-C level reduction)
- Proven cardiovascular benefit in outcome trials (eg, FOURIER and ODYSSEY OUTCOMES)
- Consider when LDL-C level remains elevated despite ezetimibe
- Injectable administration (biweekly or monthly)
- Bempedoic acid
- Newer oral agent that inhibits ATP citrate lyase
- Provides 15% to 25% LDL-C level reduction
- May be better tolerated than statins (inactive in skeletal muscle)
- Consider as add-on therapy or alternative to ezetimibe
- Inclisiran
- Small interfering RNA therapy targeting PCSK9
- Provides approximately 50% LDL-C level reduction
- Administered every 6 months after initial dosing
- Consider for patients with adherence concerns
Decision-Making Factors for Therapy Initiation/Escalation
Risk Assessment
- Higher-risk patients (e.g., those with recent acute coronary syndrome, multiple events, diabetes, or polyvascular disease) warrant more aggressive therapy.
- Consider absolute LDL-C level and distance from goal
- Assess comorbidities that may influence medication selection
Patient-Specific Considerations
- Medication cost and insurance coverage
- Patient preference for oral vs injectable therapy
- Adherence history and barriers to adherence
- Age and life expectancy
- Renal function (relevant for some therapies)
Monitoring Approach
- Assess LDL-C level response 4 to 12 weeks after therapy initiation
- Consider escalation if insufficient response
- Monitor for adverse effects with each therapy
Impact of Newer Therapies on Treatment Paradigms
Evolving Treatment Algorithms
- Shift from statin-centric to pathway-focused approach
- More personalized therapy selection based on patient characteristics
- Earlier consideration of combination therapy in high-risk patients
Practical Considerations
- Stepwise approach still recommended: ezetimibe first, followed by more expensive therapies
- Consider cost-effectiveness and sustainability of treatment
- Balance aggressive LDL-C level lowering with practicality and adherence
Conclusion
Treating statin-intolerant patients postcardiac event requires a personalized approach. While statins remain a first-line therapy, effective alternatives exist. Treatment decisions should balance cardiovascular risk reduction, tolerability, cost, and patient preferences to optimize outcomes.
