Lipid lowering therapies




The most commonly used drug class for LDL-C lowering.



Statins inhibit HMG-CoA reductase, a key enzyme in cholesterol synthesis, and reduce intrahepatic cholesterol levels, causing up regulation of hepatic LDL receptors and enhance clearance of atherogenic lipid particles from the blood.



The increased expression of hepatic LDL receptors is a common mechanism for most of the drugs used for lipid lowering.



Depending upon the potency and dose, statin therapy leads to a 20-60% reduction in LDL-C for most patients.



There is a consistent relative ASCVD risk reduction of 20-25% per 39 mg/deciliter reduction in LDL-C that has been demonstrated across most patient sub groups, with low rates of rhabdomyolysis (1/10,000 per year)and incident diabetes (1-3/10,000 person years).



About five–10% of patients experience statin associated myalgias or other skeletal muscle adverse events.



Some patients do not have adequate LDL-C reduction with maximum tolerated doses and require additional agents.






Ezetimbe reduces intestine absorption of cholesterol, which causes increased hepatic LDL-receptor and an average 10-20% reduction in serum LDL – C levels.



It is a reasonable first adjunctive medication to statin therapy.



In conjunction with moderate intensity statin it lowers ASCVD risk by 2% in patients  treated for secondary prevention over seven years of follow up.



It is unknown if it is used as a monotherapy that it can reduce ASCVD risk.



PCSK-9 inhibitors



It is a protein that marks LDL- receptor for degradation.



It increases LDL-R density and subsequently decreases serum cholesterol levels.



These agents are human monoclonal antibodies that are administered in injectable form every 2-4 weeks.



PCSK- 9 inhibitors reduce LDL-C by 50-60% when administered as mono therapy or when added to baseline statin therapy.



PCSK-9 inhibitors are associated with a 15% relative risk reduction when added to statin therapy in high-risk patients with LDL-C values above 70 mg/dL.



These agents are well tolerated with common adverse events being injection site erythema and malaise.



Bempedoic acid



It orally administered agent that Inhibits the same cholesterol biosynthetic pathway as statins, leading to of regulation of LDL-receptor density.



It lowers LDL-C by about 20%.



It has a low incidence of myalgias.



It is a good alternative or adjective medication in patients who cannot tolerate adequate statin doses or who do not achieve optimal LDL-C  lowering with statins.



Icosapent ethyl



A highly purified form of eicosapentatonic acid which is a synthetic derivative of eicosapentatonic,  one of the predominant omega three fatty acids found in fish oil.



It’s mechanism of action is unclear.



When added to statins for a secondary or high risk primary prevention with triglycerides between 135 and 500 mg/dL at a daily dose of 2 g orally b.i.d., it reduces relative ASCVD risk by 25% (4.8% absolute risk reduction over 4.8 years of follow up).



Its benefits do not appear to be related to lipid fraction changes.



Major adverse effects or in frequent with a slightly higher risk for atrial fibrillation.







An anti-sense oligonucleotide that targets specific messenger RNA sequences to disrupt translation and production of specific proteins. 



It targets only intrahepatic PCSK-9 RNA.



Clinical trials revealed durable 30-60% reduction in LDL-C with 1 to 3 injections over a three month period, followed by dosing once every six months.



Adverse events are rare.












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