Advances with lipid-lowering drugs for pediatric patients with familial hypercholesterolemia

Treatment of Dyslipidaemia in Children

“…At present, statins have supplanted bile acid sequestrants as the first-line pharmacological therapy for children with dyslipidaemia. By inhibiting 3-hydroxy-3-methylglutaryl-CoA reductase (HMG-CoA reductase, which is the rate-limiting enzyme of the hepatic cholesterol production), statins reduce the intracellular cholesterol amount, which leads to the upregulation of the LDL-C receptor on the hepatocyte’s surface and increases LDL-C catabolism [ 53 ]. In adults, it is well known that statins are safe and effective at reducing cardiovascular morbidity and mortality in both primary and secondary prevention [ 54 ].…”

“…There are currently seven approved statins for use in children and adolescents: lovastatin (the first HMG-CoA reductase inhibitor), simvastatin, atorvastatin and fluvastatin are indicated for children and adolescents ≥10 years old; pitavastatin and pravastatin have been approved for use in children from 8 years old; rosuvastatin is indicated in children as young as 6 years old [ 53 ]. The choice of the statin can be influenced by healthcare provider preferences, baseline LDL-C concentrations, treatment goals and expected LDL-C reduction with a particular formulation [ 10 ].…”

“…When used early, statins considerably reduce the cardiovascular risk of HoFH patients, changing the natural history of the disease and improving the prognosis. Although statins alone are rarely sufficient for achieving the LDL-C goals, they represent the pillar of the treatment of HoFH patients [ 53 ].…”

“…This also applies to those rare patients who develop an intolerance to HMG-CoA reductase inhibitor. If the LDL-C goals are not attained, before adding second-line therapeutic drugs, it is possible to increase the dose of statin or switch to a more potent statin, such as rosuvastatin or atorvastatin [ 53 ]. Moreover, it is extremely important to closely monitor the adherence to treatment among patients with a poor response [ 67 ].…”

“…Despite the additive lipid-lowering effect of bile acid sequestrants upon statins, these drugs are not frequently used. Cholestyramine, in particular, is associated with poor palatability and gastrointestinal effects (diarrhoea, nausea, abdominal pain, vomiting), and poor tolerance as a consequence [ 53 ]. It is also important to note that, contrary to ezetimibe, bile acid sequestrants may also affect the intestinal absorption of fat-soluble vitamins, such as vitamin D [ 73 ].…”