A 65-year-old male presents with arthralgia and sleep disturbance following the introduction of simvastatin...

A 65-year-old male presents with arthralgia and sleep disturbance following the introduction of simvastatin. He has a history of hypertension and ischemic heart disease for which he is receiving aspirin, atenolol and eprosartan together with simvastatin 40 mg once daily, which has been introduced in the last one month. Previously, he had been taking atorvastatin but this was changed to simvastatin after he complained of arthralgia.

Investigations reveal:
Creatine Phosphokinase (CPK) 156 iu/l (40-170)
Total Cholesterol 5.1 mmol/l (<5.2)
LDL-Cholesterol 3.1 mmol/l (<2.6)
Triglycerides 1.7 mmol/l (0.5-1.7)
HDL-Cholesterol 1.2 mmol/l (0.7-1.7)

Which is the most appropriate treatment for his lipid profile?
A- Ezetimibe
B- Fenofibrate
C- Nicotinic acid slow release
D- Omega-3 fatty acids
E- Rosuvastatin

Answer:
A- Ezetimibe

Discussion: The primary treatment target in this case is a total cholesterol < 4 mmol/l and LDL - C < 2 mmol/l. Plasma triglyceride and HDL-C are already at the currently accepted target levels. This patient describes typical statin associated side effects which are generally a class effect and dose related. The most common adverse event with statin therapy is athralgia or myopathy often with normal CPK levels. Myositis and rhabdomyolysis are rare statin associated myopathy side effects and are defined on the basis of CPK levels > 10X normal along with features of muscle pain and myoglobinuria (for rhabdomyolysis). Risk factors predisposing to statin myopathy include advanced age, trauma, thyroid dysfunction and concomitant medication that can raise statin bioavailability including amiodarone, verapamil and many other agents that are metabolised by the Cytochrome P450 enzyme system.

Ezetimibe montherapy produces reductions in TC and LDL-C of around 20% and since tolerability issues are likely to occur with another statin, ezetimibe is the best treatment option. Clinical trial data has demonstrated continuing event rate reduction to LDL-C levels below 2 mmol/l and a meta-analysis of lipid lowering trials has demonstrated a 1 mmol/l reduction in LDL-C is associated with a 23% RRR in CHD events irrespective of baseline risk and the method of cholesterol reduction.