Antihyperlipidemic Drugs: Lowering Lipids To Reduce Cardiovascular Risk


Hyperlipidemia or high levels of lipids in the blood is a major risk factor for developing cardiovascular diseases like atherosclerosis, heart attack and stroke. Antihyperlipidemic drugs help lower elevated lipid levels and reduce cardiovascular risk. In this article, we discuss the various classes of antihyperlipidemic drugs available and their efficacy.

Statins: The First Line of Treatment
Statins are considered first-line treatment for hyperlipidemia due to their proven efficacy in reducing cardiovascular risk. Statins work by competitively inhibiting HMG-CoA reductase, the rate-limiting enzyme in cholesterol biosynthesis. This leads to upregulation of LDL receptors in the liver, increased clearance of LDL-cholesterol from blood and reduced levels. Some commonly prescribed statins include Atorvastatin, Rosuvastatin, Simvastatin, Pravastatin etc. Statins can reduce LDL-C levels by 20-60% depending on the drug and dosage. They also mildly reduce triglyceride levels while increasing HDL-C levels. Large clinical trials have shown that statin therapy reduces the risk of heart attacks and strokes by around 25-35%. However, some patients experience muscle pain or weakness (myalgia) as a side effect which limits their use.

PCSK9 Inhibitors: A Promising New Class
Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are a new class of injectable drugs for patients who cannot achieve adequate LDL-C reduction with statins or are statin intolerant. PCSK9 binds to LDL receptors and targets them for degradation, thereby reducing cholesterol clearance from blood. PCSK9 inhibitors block this interaction leading to increased number of LDL receptors and enhanced LDL lowering. Evolocumab and Alirocumab are two PCSK9 inhibitors approved for clinical use. They can further lower LDL-C levels by 50-60% when added to statins. Clinical trials have demonstrated their ability to significantly reduce cardiovascular events like heart attacks. However, their high cost limits widespread use currently.

Antihyperlipidemic Drugs are pharmaceutical agents used to lower elevated levels of lipids, such as cholesterol and triglycerides, in the blood. These medications include statins, fibrates, bile acid sequestrants, PCSK9 inhibitors, and cholesterol absorption inhibitors. They help mitigate the risk of cardiovascular diseases by regulating lipid metabolism and improving lipid profiles.

Bile Acid Sequestrants: Useful but inconvenient
Bile acid sequestrants like Colesevelam and Colestipol work by binding bile acids in the intestine. This prevents bile acid reabsorption and increases elimination from body. To compensate for the higher bile acid loss, liver pulls more cholesterol from blood to synthesize new bile acids. This lowers LDL-C levels by 15-20%. They also mildly reduce triglyceride levels. Side effects may include constipation and intestinal gas. Taking the drug with meals helps reduce these symptoms. However, their large pill size and 3-4 times daily dosing limits compliance. Reserving them for patients who cannot tolerate other drugs is reasonable.

Ezetimibe: Fills a useful niche
Ezetimibe works by inhibiting intestinal cholesterol absorption. It blocks the Niemann-Pick C1-Like 1 protein which transports cholesterol across enterocytes. Ezetimibe alone lowers LDL-C by 15-20% and provides additional benefit when added to statin therapy. Combining ezetimibe with a statin provides greater LDL-C lowering of up to 55% without added side effects. It has a favorable safety profile. Ezetimibe fills an important role as additive therapy in patients not meeting LDL-C goals with maximum tolerated statin alone or those who are statin intolerant.

Fibric Acid Derivatives: Help manage hypertriglyceridemia
Fenofibrate, Gemfibrozil and Bezafibrate are fibric acid derivatives mainly used to lower elevated triglyceride levels. They work by activating peroxisome proliferator-activated receptor alpha (PPAR-α) in the liver to stimulate breakdown and clearance of triglyceride-rich lipoproteins from blood. They reduce triglyceride levels by 20-50% and also mildly increase HDL-C levels. However, they have limited effects on lowering LDL-C. These drugs are preferred for isolated hypertriglyceridemia or mixed dyslipidemia associated with elevated triglyceride levels. Side effects may include gastrointestinal distress and impaired kidney function with gemfibrozil.

Niacin: Broad-spectrum but tolerability issues
Niacin or nicotinic acid is a water-soluble B vitamin which reduces all atherogenic lipid particles when taken at high doses. It can lower LDL-C by 15-25%, triglycerides by 20-50% and increase HDL-C significantly by 15-35%. However, it frequently causes uncomfortable flushing, itching and other side effects that reduce tolerability. Sustained-release or extended-release preparations help reduce flushing. Niacin generally finds limited use due to tolerability concerns unless necessary for refractory high triglyceride or low HDL-C levels.

Various classes of antihyperlipidemic drugs available based on the predominant lipid target aid in reducing cardiovascular risk. Statins remain first-line therapy while other drugs fill useful adjunctive roles alone or in combination for optimum LDL-C lowering and risk reduction. Lifestyle changes and addressing secondary causes additionally help good lipid control.

1. Source: Coherent Market Insights, Public sources, Desk research
2. We have leveraged AI tools to mine information and compile it