Benefits and risks assessment of simvastatin in familial hypercholesterolaemia

Abstract

Familial hypercholesterolaemia (FH) is a frequent inherited monogenic disorder, associated with premature coronary artery disease. Life expectancy of FH patients is reduced by 15 - 30 years unless they are adequately treated with lipid-lowering therapy. Patients with this disorder need long-term drug therapy and the selection of treatment should be strongly based on its long-term safety and tolerability. The introduction of 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors has changed the treatment of FH. Simvastatin 40 - 80 mg/day effectively reduces serum low-density lipoprotein cholesterol levels, and also reduces triglycerides with a modest rise in high-density lipoprotein cholesterol levels. Other potentially important effects, such as improvement of endothelial function, reduction of LDL oxidation and vascular inflammation, have been associated with simvastatin therapy in FH. In addition, simvastatin has been shown to abolish the progression, and even facilitate the regression of existing human atherosclerotic lesions. The safety and tolerability of simvastatin is clearly highlighted by the low rate of therapy discontinuation observed in several population-based clinical trials. Asymptomatic elevations in liver transaminase levels and myopathy are uncommon. The efficacy and tolerability of simvastatin at doses up to 80 mg/day are well-established, as well as its cost-effectiveness in the management of FH patients.

Comparison of the efficacy and safety of an oral combination of losartan, hydrochlorothiazide and simvastatin against separated components, in hypertensive and dyslipidemic patients

“…Losartan induces uricosuric and hyperkalemic effects (Ripley and Hirsch, 2010), while thiazide diuretics as hydrochlorothiazide can provoke hyperglycaemia and diabetes, as well as hypokalemia and hyperuricemia (Palmer, 2011). Simvastatin, as other statins, has been associated with rare cases of severe myopathy and rhabdomyolysis, which is accompanied by elevations in creatine kinase, as well as renal failure (Alonso et al, 2005). In this fixeddose combination, some adverse events are counterbalanced as earlier stated, but patients should be monitored for creatine kinase activity, as well as for creatinine, uric acid, glucose and K + levels.…”

Optimal management of familial hypercholesterolemia: treatment and management strategies

“…The other category of drugs that have been used effectively in adults with hypercholesterolemia are hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors 25–27. Statins have also shown favorable results and safety profile in adolescents, although response to these drugs is reported to be dependent on LDL receptor genotype 28,29.…”

Quality of Life and Its Contributing Factors in Patients with Familial Hypercholesterolaemia in Malaysia

“…Worldwide, the prevalence of FH is around 1: 500-200, while it is more common in the Malaysian population with an estimated frequency of 1:100 (Vallejo-Vaz et al, 2018). If untreated, FH patients will suffer reduced life expectancy by up to 30 years compared those without FH (Alonso, Mata, & Mata, 2005).…”