What is the efficacy of each lipid-lowering drug, such as statins (HMG-CoA reductase inhibitors) and fibrates, in reducing hyperlipidemia?

From the Guidelines

Statins are the most effective lipid-lowering drugs, reducing LDL cholesterol by 20-60% depending on the specific medication and dose, and should be used as the first-line pharmacologic therapy for LDL lowering. The efficacy of lipid-lowering drugs can be broken down as follows:

• Statins: reduce LDL cholesterol by 20-60% depending on the specific medication and dose, with high-intensity statins like atorvastatin 40-80mg or rosuvastatin 20-40mg daily lowering LDL by 50% or more 1.
• Ezetimibe: typically reduces LDL by 15-20% when used alone and provides an additional 15-20% reduction when combined with statins.
• PCSK9 inhibitors (evolocumab and alirocumab): are highly potent, lowering LDL by 50-70% beyond statin therapy.
• Bile acid sequestrants (cholestyramine, colestipol): reduce LDL by 15-30% but have limited use due to gastrointestinal side effects.
• Fibrates (fenofibrate, gemfibrozil): primarily lower triglycerides by 30-50% with modest 5-15% LDL reduction, and have been shown to reduce CVD rates and progression of carotid intimal medial progression in patients with low HDL 1.
• Niacin: can reduce LDL by 15-20% and triglycerides by 20-40% while raising HDL by 15-30%, though side effects limit its use.
• Omega-3 fatty acids: mainly reduce triglycerides by 20-50% at prescription doses (4g daily).
• Bempedoic acid: lowers LDL by 15-25% and can be useful for statin-intolerant patients.
• Inclisiran: provides sustained LDL reduction of 50-55% with twice-yearly injections.

The selection of lipid-lowering drugs should be based on lipid profile, cardiovascular risk, comorbidities, and tolerability, as recommended by the 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol 1.

From the FDA Drug Label

Ezetimibe Tablet reduces total-C, LDL-C, Apo B, and non-HDL-C in patients with hyperlipidemia. Maximal to near maximal response is generally achieved within 2 weeks and maintained during chronic therapy In two multicenter, double-blind, placebo-controlled, 12-week trials in 1719 patients with primary hyperlipidemia, ezetimibe tablet significantly lowered total-C, LDL-C, Apo B, and non-HDL-C compared to placebo Combination with Statins: Ezetimibe Tablet Added to On-going Statin Therapy In a multicenter, double-blind, placebo-controlled, 8-week trial, 769 patients with primary hyperlipidemia, known coronary heart disease or multiple cardiovascular risk factors who were already receiving statin monotherapy but who had not met their NCEP ATP II target LDL-C goal, were randomized to receive either ezetimibe tablet or placebo in addition to their on-going statin. Ezetimibe Tablet, added to on-going statin therapy, significantly lowered total-C, LDL-C, Apo B, and non-HDL-C compared with a statin administered alone

The efficacy of ezetimibe in reducing hyperlipidemia is supported by clinical trials, which show that it significantly lowers total-C, LDL-C, Apo B, and non-HDL-C in patients with primary hyperlipidemia.

• The reduction in LDL-C was consistent across age, sex, and baseline LDL-C.
• When added to ongoing statin therapy, ezetimibe further lowered total-C, LDL-C, Apo B, and non-HDL-C compared to statin alone 2.

Fenofibrate is mainly excreted in the urine in the form of metabolites, primarily fenofibric acid and fenofibric acid glucuronide. The pharmacokinetics of fenofibric acid was examined in patients with mild, moderate, and severe renal impairment. Patients with severe renal impairment (estimated glomerular filtration rate [eGFR] < 30 mL/min/1.73m2) showed 2. 7-fold increase in exposure for fenofibric acid and increased accumulation of fenofibric acid during chronic dosing compared to that of healthy subjects.

The efficacy of fenofibrate in reducing hyperlipidemia is not directly stated in the provided text, but it is mentioned that fenofibrate is a lipid-lowering agent and its pharmacokinetics are affected by renal impairment 3.

However, the provided text does not directly compare the efficacy of statins and fibrates in reducing hyperlipidemia.

• Statins are mentioned as part of combination therapy with ezetimibe, but their individual efficacy is not directly addressed in the provided text.
• Fibrates, such as fenofibrate, are mentioned as lipid-lowering agents, but their efficacy in reducing hyperlipidemia is not directly compared to statins in the provided text.

From the Research

Efficacy of Lipid-Lowering Drugs

The efficacy of lipid-lowering drugs, such as statins and fibrates, in reducing hyperlipidemia is well-documented in various studies 4, 5, 6, 7, 8.

• Statins are the first-line treatment for reducing cardiovascular events by lowering low-density lipoprotein cholesterol (LDL-C) levels, with a reduction of 30-50% 6.
• The addition of ezetimibe to statin therapy can further reduce LDL-C levels by about 20% 4, 5, 7.
• Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, such as evolocumab and alirocumab, can reduce LDL-C levels by ≥50% when added to statins 4, 6, 8.
• The combination of rosuvastatin and ezetimibe has been shown to be effective in reducing LDL-C levels and achieving lipid goals in high-risk patients, while avoiding safety issues related to high dosages of intensive statin therapy 7.

Comparison of Lipid-Lowering Drugs

A comparison of the efficacy and safety of different lipid-lowering drugs is presented in the following points:

• Statins are the most potent drugs for lowering LDL-C levels, but may not be enough to achieve LDL-C goals in many patients 5, 6.
• Ezetimibe is usually the first additional treatment to achieve LDL-C targets, with a reduction of about 20% 4, 5, 7.
• PCSK9 inhibitors have been shown to be effective in reducing atherosclerotic events through their significant LDL-C-lowering action, and are considered safe and well-tolerated 6, 8.
• The safety and tolerability of injectable lipid-lowering drugs, such as evolocumab, alirocumab, and inclisiran, have been established in clinical studies 6.