What is the best course of action for a patient with familial hypercholesterolemia who requests to stop lipid-lowering therapy, including rosuvastatin (statin) and ezetimibe, due to muscle fatigue after implementing lifestyle changes?

Management of Lipid-Lowering Therapy in Familial Hypercholesterolemia

Continue both rosuvastatin and ezetimibe (Option c) without interruption, as familial hypercholesterolemia is a lifelong genetic condition requiring continuous aggressive lipid-lowering therapy regardless of lifestyle improvements, and the muscle fatigue is likely unrelated to statin therapy. 1

Rationale for Continuing Combination Therapy

Familial Hypercholesterolemia Requires Lifelong Treatment

• Familial hypercholesterolemia is a genetic disorder with both parents showing premature atherosclerosis, placing this patient at extremely high cardiovascular risk that persists despite lifestyle modifications 2
• Discontinuing therapy in FH patients would result in rapid return to dangerously elevated LDL-C levels and accelerated cardiovascular disease progression 3, 4
• The combination of rosuvastatin and ezetimibe is specifically indicated for heterozygous familial hypercholesterolemia and provides complementary mechanisms of LDL-C reduction 2, 5

Current Lipid Control Remains Inadequate

• While improvements have occurred, the patient has not achieved the aggressive LDL-C targets required for familial hypercholesterolemia patients 1
• High-risk FH patients require LDL-C <55 mg/dL (<1.4 mmol/L) to adequately reduce cardiovascular mortality and morbidity 1
• The current regimen should be maintained and potentially intensified rather than reduced 1

Addressing the Muscle Fatigue Concern

Muscle Symptoms Are Likely Not Statin-Related

• True statin-induced myopathy occurs in only 1% of patients, and awareness of potential side effects often causes subjective symptoms more than the medication itself 1
• The patient's muscle fatigue occurs specifically after intense workouts (exercise-induced), not at rest or with routine activities, which is inconsistent with statin myopathy 6, 7
• Recent intensification of training (biking and running regularly) is the most likely cause of training plateau and muscle fatigue 6

Diagnostic Approach to Muscle Symptoms

• Check creatine kinase (CK) levels and thyroid-stimulating hormone to objectively assess for true myopathy 6, 7
• If CK is <4× upper limit of normal and the patient is asymptomatic at rest, continue current therapy with monitoring 6
• Only if CK is >10× upper limit of normal with severe symptoms should statin discontinuation be considered 7

Why Other Options Are Inappropriate

Stopping Rosuvastatin Alone (Option a) Is Inadequate

• Ezetimibe monotherapy provides insufficient LDL-C reduction for familial hypercholesterolemia patients 5, 3
• The combination of statin plus ezetimibe is standard of care for FH, with rosuvastatin providing the foundation of therapy 1, 4

Stopping All Medications (Option b) Is Dangerous

• Discontinuing lipid-lowering therapy in FH patients dramatically increases risk of premature myocardial infarction, stroke, and cardiovascular death 1, 4
• Lifestyle modifications alone cannot overcome the genetic defect causing familial hypercholesterolemia 4
• The strong family history of premature atherosclerosis mandates aggressive pharmacotherapy 1

Switching to PCSK9 Inhibitor (Option d) Is Premature

• PCSK9 inhibitors are reserved for FH patients who fail to achieve targets on maximum tolerated statin plus ezetimibe therapy 1
• There is no documented statin intolerance in this patient (no objective evidence of myopathy) 1, 7
• The current combination should be optimized before considering more expensive and invasive injectable therapy 1

Optimal Management Strategy

Continue Current Medications

• Maintain rosuvastatin and ezetimibe at current doses, as this combination is safe, effective, and specifically indicated for familial hypercholesterolemia 1, 2, 8
• The combination of rosuvastatin with ezetimibe has comparable safety to rosuvastatin monotherapy while providing superior LDL-C reduction 1, 8

Consider Dose Optimization

• If LDL-C remains above target (<55 mg/dL), consider increasing rosuvastatin dose or adding bempedoic acid before discontinuing any therapy 1
• The combination of ezetimibe with rosuvastatin can achieve up to 65% LDL-C reduction from baseline in FH patients 5

Patient Education and Monitoring

• Explain that muscle fatigue from intense exercise is expected and unrelated to statin therapy 1, 6
• Counsel that familial hypercholesterolemia requires lifelong therapy regardless of lifestyle improvements 4
• Schedule lipid panel assessment in 4-6 weeks if any dose adjustments are made, otherwise annually once stable 1, 9
• Monitor CK only if muscle symptoms worsen or occur at rest 6, 7

Common Pitfalls to Avoid

• Do not discontinue effective lipid-lowering therapy based on subjective muscle complaints without objective evidence of myopathy (elevated CK) 1, 6
• Do not attribute exercise-related muscle fatigue to statins when the patient has recently intensified training 6
• Do not underestimate the lifelong cardiovascular risk in familial hypercholesterolemia patients, even with lifestyle optimization 1, 4
• Avoid the misconception that lifestyle changes can replace pharmacotherapy in genetic lipid disorders 4