PCSK-9 Inhibitors in a Real-World Setting and a Comparison Between Alirocumab and Evolocumab in Heterozygous FH Patients.

A real-world setting study of familial hypercholesterolemia (FH) patients who received Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors in a specialized referral center in Mexico City. Ten patients between the ages of 18 and 70 years, with a diagnosis of FH according to Dutch Lipid Clinic Network (DLCN) criteria, with failure to achieve their Low-density lipoprotein Cholesterol (LDL-C) goals, and with standard therapy between 2016 and 2017 enrolled in a simple randomization in which a group of 5 participants received alirocumab (75 mg every 2 weeks) and the remaining 5 patients received evolocumab (140 mg every 2 weeks). Comparative analysis was made, analyzing the means of LDL at baseline at 4, 6, and 12 weeks. The evolocumab group had an average initial LDL-C of 277 mg/dL, which, after 12 weeks of treatment, was significantly reduced to 116 mg/dL; P = 0.04 (95% confidence interval [CI]: 11.5-310.9). The alirocumab group with a mean initial LDL-C of 229 mg/dL showed a reduction of LDL-C levels at 12 weeks of treatment to 80 mg/dL; P = 0.008 (95% CI: 63.8-233.7). In conclusion, PCSK9 inhibitors are an excellent treatment option in patients with FH who do not reach their LDL-C goals with standard therapy or due to intolerance to the standard therapy. There is no difference in the lipid-lowering effect between both PSCK9 inhibitors.

Inhibición de PCSK9: una nueva alternativa para reducir el colesterol y prevenir la enfermedad cardiovascular aterosclerosa / Inhibition of PCSK9: a new alternative for cholesterol reduction and prevention of atherosclerotic cardiovascular disease

Resumen La enfermedad cardiovascular aterosclerosa ocupa el primer lugar mundial en morbilidad y mortalidad. El principal factor de riesgo de enfermedad es el colesterol unido a lipoproteínas de baja densidad (C-LDL). El tratamiento farmacológico de elección para reducir el C-LDL son las estatinas; sin embargo, han sido insuficientes para eliminar el riesgo cardiovascular, especialmente en pacientes con formas primarias de hipercolesterolemia relacionadas con mutaciones genéticas, o intolerantes a estatinas. Es de gran importancia el desarrollo de nuevos fármacos para abatir el riesgo que persiste a pesar de la administración de estatinas. La proconvertasa subtilisina-kexina 9 (PCSK9) es un regulador primordial de la cantidad de receptores de LDL, ya que su función es dirigir dichos receptores a su destrucción lisosomal. El advenimiento de anticuerpos monoclonales para bloquear la PCSK9 ha permitido mejorar la cantidad y eficiencia de los receptores de LDL, de esto resulta la disminución notable del colesterol circulante. Hasta el momento, la eficacia e inocuidad de estos anticuerpos resultan aceptables, y los datos preliminares en cuanto a su efecto en la reducción de la morbilidad y mortalidad cardiovasculares son alentadores.

Abstract Atherosclerotic cardiovascular disease represents the leading cause of morbidity and mortality in most countries. The main risk factor for developing this disease is low density lipoprotein cholesterol (LDL-C). The pharmacological treatment of choice for reducing LDL-C is statins; however, in spite of the widespread use of statins, these drugs have been insufficient to eliminate cardiovascular risk. This residual risk is most relevant in patients with primary forms of hypercholes-terolemia associated with genetic mutations, or in those who are intolerant to statins. The development of new drugs to reduce residual cardiovascular risk is of vital importance. Proprotein convertase subtilisin-kexin 9 (PCSK9) is an important regulator of the amount of LDL receptors since its function is to direct these receptors to their lysosomal destruction. The development of monoclonal antibodies to block extracellular PCSK9 has allowed us to improve the quantity and efficiency of LDL receptors, resulting in a significant decrease in plasma cholesterol. Efficacy and safety of these antibodies is currently considered acceptable and preliminary data are encouraging but still insufficient to assess the favorable impact of these antibodies in reducing cardiovascular morbidity and mortality.

Will the PCSK9 Inhibitors Be Employers' "Line in the Sand"?

After the introductions of sofosbuvir (Sovaldi) and ledipasvir plus sofosbuvir (Harvoni) for the treatment of hepatitis C, employers have become very sensitive to new, and especially unforeseen, factors that significantly raise healthcare costs. With the recent launch of the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, self-insured and fully insured employers have been seeking information on this drug class and its potential for off-label use, which could amount to up to $23 billion in healthcare expenditures, according to a report from Prime Therapeutics. Based on their approved indications, 0.4% of commercial members may be eligible to use PCSK9 inhibitors, at a cost of $3.29 per member per month. Corporate employers are evaluating their options to manage the new expense associated with the novel PCSK9 inhibitors.