Endocrine Abstracts

Introduction: PCSK-9 (proprotein convertase subtilisin/kexin type 9) inhibitors are monoclonal antibodies that affect metabolism of low-density lipoprotein (LDL) by binding to the LDL receptor and promoting lysosomal degradation. There are two pcsk-9 inhibitors currently available: alirocumab (Praulent) and evolocumab (Repatha) which are administered subcutaneously every 14 days. Two large randomized studies (FOURIER, ODYSSEY) have shown that pcsk-9 inhibitors reduce LDL-cholesterol levels by 50-60% and additionally lipoprotein (a) levels by 25-30%. Such results broadened the indications for the usage of pcsk-9 inhibitors. Since serum levels of lp (a) is exclusively genetically determined, the possibility of its reduction is very important as high serum lp(a) levels increase cardiovascular risk by up to three-fold. Lowering of lp(a) levels is especially important for younger patients with cardiovascular incident in history Although the mechanism how pcsk-9 inhibitors reduce lp (a) levels is unclear, some studies show that at lower LDL-cholesterol levels, lp (a) levels decrease more with the assumption of better competence for LDL-receptor site.

Methods and results: Polyclinic of Reference Center for Rare and Metabolic Diseases has a total of 51 patients on PCSK-9 inhibitor therapy which was indicated due to elevated lp (a) concentration (>75 nmol/l,>0.5 g/l). The average age of patients is 52.74 years with almost equal distribution of male and female gender (53%, 47%). The overall percentage in reduction of lp(a) levels during 3 months of PCSK-9 inhibitor therapy was 30.78%, with a maximum reduction of 72% and a minimum of 5%. T-test of paired samples for the effect of pcsk-9 inhibitors on the reduction of lp(a) concentration revealed a statistically significant difference (t=5,2015; P= 0.00000156,<0.0001) at serum lp(a) concentrations before (M=127.05, SD=133.93) and after pcsk-9 inhibitor therapy (M=82.29, SD=81.06). The strength of the test is 0.982. The maximum observed reduction of 72% was observed in a patient who was previously on the statin therapy at the maximum dosage.

Conclusion: The experience of our Center confirms previous research on the effect of pcsk-9 inhibitors on the reduction of lp (a) concentration by 30%. Comparing targeted concomitant therapy, we have observed a trend of greater reduction in lp (a) levels with pcsk-9 inhibitor therapy in patients who are previously on the maximum statin dose, suggesting possible metabolism of the particle itself via the LDL receptor by the mechanism of competition.

Keywords lipoprotein (a), PCSK-9 inhibitors, statins