PCSK9 inhibitors

Class of cholesterol lowering medications.

Proprotein convertase subtilisin/Kevin type 9 inhibitors- monoclonal antibodies.

PCSK9 is a protein that normally functions to reduce receptors on the surface of liver cells that remove LDL cholesterol from the blood.

PCSK9 inhibitors are monoclonal antibodies that increase hepatic LDL receptors, decrease LDL level, and reduce cardiovascular events when combined with statins.

When PCSK9 is blocked, more receptors are available to eliminate LDL-cholesterol and lower blood levels of bad cholesterol.

The binding of proproteins convertase subtilisin-Kexin type 9 (PCSK9) in the circulation of monoclonal antibodies reduces both low density lipoprotein cholesterol levels and the incidence of cardiovascular events.

Promote degradation of LDL receptors thereby diminishing the clearance of LDL from the circulation.

Humanized monoclonal antibodies that inactivate the proprotein convertase subtilisin-Kexin type nine (PCSK9).

PCSK9 mutations conveying gain or loss of function result in higher or lower levels of LDL cholesterol, respectively which in turn is associated with correspondingly higher or lower risk of incident coronary heart disease.

Evolocumab, Aliricumab.

For use in addition to maximally tolerated statin therapy with familial hypercholesterolemia for atherosclerotic cardiovascular disease who require additional lowering of LDL cholesterol levels.

Should be considered in patients who is LDL -C levels do not drop lower than 70 mg/dL with statins and ezetimibe or whose non–HDL-C levels are over 100 mg/dL or higher, adding a proprotein convertase subtilisin/lexin type 9 inhibitor is an option.

PCSK9 is secreted by the liver and is found in one in every 500 LDL particles in the circulation.

When PCSK9 associated particles bind to the LDL receptor, the complex is internalized and the receptor is targeted for degradation rather than recycling back to the cell surface.

PCSK9 inhibitors mimic mechanism of action involves both accelerated removal and decreased production of LDL particles.

Injected subcutaneously every 2-4 weeks.

Wholesale price ranges between 14,100-14,600 per year.

Differences clinically between the two agents is minimal.

Both agents are given by injection and cause large reductions in LDL cholesterol levels as compared to placebo-39 to 62% reduction for alirocumab and 47-56% for evolocumab.

Studies indicate approximately 37% of patients receiving evolocumab and 24% of patients receiving alirocumab dropped below 25 mg/dL on two consecutive measurements of LDL-cholesterol.

GAUSS-3 trial-year-enrolled patients with elevated LDL levels unable to tolerate effective doses of  statins: evolocumab compared with ezetimbe resulted in a significantly greater reduction in LDL-C levels at 24 weeks.

In patients with previous acute coronary syndrome (ACS), adding alirocumab to high-intensity statin therapy was associated with a reduction in the risk of recurrent ischemic cardiovascular events.

ODYSSEY OUTCOMES trial revealed that among patients who had a previous acute coronary syndrome and who were receiving high intensity statin therapy, the risk of recurrent ischemic cardiovascular events was lower among those who received alicumab than among those who receive placebo.

OSLER trials Showed that the addition of evolocumab to standard therapy resulted in an LDL cholesterol level that was 61% lower than the level with standard therapy.

Inclisiran reduced LDL cholesterol levels of approximately 50% when administered subcutaneously every six months.

Among patients with acute MI the addition of subcutaneous biweekly alirocumab, compared with placebo, to high intensity statin  therapy resulted in significantly greater coronary plaque regression in non-infarct related arteries after 52 weeks (Raber L).

Leave a Reply

Your email address will not be published. Required fields are marked *