Familial hypercholesterolemia (FH) is often called the “silent accelerant” of cardiovascular risk. From early in life, patients carry LDL-C levels that standard therapy rarely brings to target, resulting in decades of cumulative cholesterol exposure and a significantly elevated risk for premature ASCVD events.
Despite this, FH remains under-recognized—fewer than 1 in 10 patients are ever diagnosed. Missed opportunities for cascade screening and delayed follow-up testing mean many families stay at risk until a major event occurs. Even when FH is identified, achieving LDL-C targets aligned with clinical guidelines remains a challenge.
Clinical data continue to support timely intensification of therapy when conventional approaches fall short. Inhibition of the PCSK9 pathway has been associated with nearly 50% reductions in LDL-C, with added improvements in ApoB and lipoprotein(a). A 2025 meta-analysis showed these effects in both adults and children with FH, reinforcing the importance of early and aggressive intervention in high-risk cases.
Yet real-world care is rarely straightforward. Some patients show a weaker-than-expected response, often linked to missed doses, elevated lipoprotein(a), or genetic variability. Others face barriers tied to access, coverage, or fragmented care, but progress depends on detection, intensification, and follow-up.
How are you identifying FH patients earlier in your practice? When do you escalate therapy—and what has helped sustain LDL-C control long term?
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• LDL-C thresholds: Persistent LDL-C ≥190 mg/dL in adults (≥160 mg/dL in children) without secondary causes is a major red flag.
• Clinical tools: Dutch Lipid Clinic Network (DLCN), Simon Broome, or MEDPED criteria can stratify the likelihood of FH based on LDL-C levels, family history, and clinical findings (xanthomas, corneal arcus).
• Cascade screening: Testing first-degree relatives of known FH patients remains the most efficient approach to uncover additional cases.
• Genetic testing: Increasingly used to confirm diagnosis and guide therapy, especially when considering PCSK9 or siRNA therapies.
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2. When to Escalate Therapy
Escalation depends on baseline LDL-C, current therapy, and residual risk:
• Start early and be aggressive: Most guidelines (AHA/ACC 2022, ESC/EAS 2023) recommend immediate high-intensity statin + ezetimibe at diagnosis.
• Add-on therapy:
• PCSK9 inhibitors (evolocumab, alirocumab) when LDL-C >70 mg/dL (ASCVD) or >100 mg/dL (FH primary prevention) despite maximal statin/ezetimibe.
• Inclisiran (siRNA PCSK9 synthesis inhibitor) for patients needing durable LDL-C lowering with less frequent dosing.
• Evinacumab (ANGPTL3 inhibitor) for homozygous FH or severe refractory heterozygous cases.
• Lipoprotein(a): If elevated, intensification or clinical trial enrollment may be appropriate.
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3. Sustaining LDL-C Control Long-Term
Sustained success depends on behavioral, clinical, and system-level supports:
• Patient education: Framing FH as a lifelong genetic condition—not just “high cholesterol”—helps improve adherence.
• Simplify regimens: Two-in-one combination pills or long-acting therapies (e.g., inclisiran every 6 months) can enhance persistence.
• Follow-up cadence: Recheck lipids 6–8 weeks after therapy change, then every 3–6 months once stable.
• Multidisciplinary coordination: Lipid clinics, genetic counselors, and pharmacists can bridge gaps between detection and therapy intensification.
• Family-based care: Coordinating screening and follow-up across relatives improves both adherence and outcomes.
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Would you like me to outline a workflow or algorithm that integrates early detection, therapy escalation, and follow-up tracking for FH patients (something you could use in clinic or presentation format)?