Saturday, November 26, 2022

Interfering RNA to Reduce Lipoprotein(a) in Cardiovascular Disease


Cardiovascular disease is the leading cause of death and disability worldwide. Lipoprotein(a) is a low-density lipoprotein variant containing a protein called apolipoprotein(a). High levels of lipoprotein(a) are a causal risk factor for atherosclerotic cardiovascular disease. It also influences inflammatory processes as well as the function of leukocytes, and vascular and cardiac cells, thereby impacting vessels and the heart. Statins form the select therapy with the aim to block cholesterol synthesis, although additional lipid-lowering drugs are required to achieve low-density lipoprotein cholesterol target values. 

A recent study has discovered that olpasiran therapy significantly reduces lipoprotein(a) concentrations in patients with atherosclerotic cardiovascular disease. Olpasiran is a small interfering RNA that reduces lipoprotein synthesis in the liver. The study conducted a randomized, double-blind, placebo-controlled, dose-finding trial in which patients with atherosclerotic cardiovascular disease and lipoprotein(a) concentration of more than 150 nmol per liter were involved. Patients were randomly assigned to receive one of four doses of olpasiran or a matching placebo. After nine months, the lipoprotein concentration had increased by a mean of 3.6% in the placebo group while olpasiran therapy had substantially and significantly reduced the lipoprotein(a) concentration in a dose-dependent manner. 

With cardiovascular disease being the leading cause of mortality and morbidity worldwide, effective and worthwhile therapies to reduce cardiovascular risk are highly needed. In so, I believe that further trials are required to determine olpasiran therapy's effect on cardiovascular disease, not just atherosclerotic cardiovascular disease.  Although from the previous trial on atherosclerotic cardiovascular disease, olpasiran therapy seems to be a promising therapy for individuals with high lipoprotein(a) levels who currently don't have any effective therapies to lower their concentration. 

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