From the Guidelines
The efficacy of triglyceride-lowering drugs varies significantly across medication classes, with fibrates, omega-3 fatty acids, and statins being the primary treatment options, as recommended by the 2021 ACC expert consensus decision pathway 1.
Triglyceride-Lowering Medications
The following medications are used to lower triglycerides:
- Fibrates (fenofibrate, gemfibrozil) typically reduce triglycerides by 30-50% and are often first-line for severe hypertriglyceridemia, as seen in the FIELD trial 1.
- Omega-3 fatty acids, particularly prescription-strength formulations like icosapent ethyl (Vascepa) at 4g daily, can lower triglycerides by 20-50%, as recommended by the 2021 ACC expert consensus decision pathway 1.
- Statins primarily target LDL cholesterol but also reduce triglycerides by 10-30%, with more potent statins like rosuvastatin and atorvastatin showing greater effects, as seen in the Heart Protection Study and the Collaborative Atorvastatin Diabetes Study 1.
Treatment Approach
For patients with severe hypertriglyceridemia (>500 mg/dL), combination therapy may be necessary, typically starting with a fibrate and adding omega-3 fatty acids, as recommended by the Endocrine Society guidelines 1.
Mechanism of Action
The mechanism of action differs among these medications:
- Fibrates activate PPAR-α receptors to enhance triglyceride clearance.
- Omega-3s reduce hepatic triglyceride production.
- Statins primarily inhibit cholesterol synthesis but also decrease triglyceride-rich lipoprotein production.
Treatment Efficacy
Treatment efficacy should be assessed after 4-12 weeks with appropriate dose adjustments as needed, taking into account the patient's cardiovascular risk factors and other comorbidities, as recommended by the 2021 ACC expert consensus decision pathway 1.
From the Research
Efficacy of Triglyceride-Lowering Drugs
The efficacy of triglyceride-lowering drugs, such as fibrates, omega-3 fatty acids, and statins, has been evaluated in several studies.
- Fibrates: According to 2, fibrates have not been able to demonstrate significant cardiovascular risk reduction in most clinical trials. However, they are still used to lower triglyceride levels.
- Omega-3 fatty acids: The study 2 mentions that only icosapent ethyl esters (a purified EPA) have shown significant cardiovascular benefit in patients with ASCVD or diabetes with elevated risk on maximally tolerated statin. Another study 3 found that prescription omega-3 fatty acids (P-OM3) reduced median TG values by 60.8% when used concomitantly with fenofibrate.
- Statins: Statins are first-line therapy for treatment of elevated triglyceride and lower ASCVD risk in patients with elevated triglycerides 2.
Comparison of Triglyceride-Lowering Therapies
- A study 3 compared the efficacy of P-OM3 plus fenofibrate with fenofibrate monotherapy in subjects with very high TG levels. The results showed a trend towards greater reduction in TG levels with the combination therapy.
- Another study 4 discussed the recent developments in pharmacotherapy for hypertriglyceridemia, including apolipoprotein C-III inhibitors, angiopoietin-like 3 inhibitors, and novel formulations of omega-3 fatty acids.
- A review 5 assessed recent evidence for TG-lowering agents, including omega-3 fatty acid-based therapies, PPARα modulators, apoC-III mRNA antisense inhibitors, and angiopoietin-like 3 (ANGPTL3) antibodies.
Current State of Triglyceride-Lowering Therapies
- The current state of triglyceride-lowering therapies is evolving, with new agents being developed to target novel pathways 4, 5.
- The choice of therapy is mainly based on baseline TG levels, and dyslipidemia guidelines are likely to change in the near future to include some of these new agents 4.
- Long-term data regarding the safety and efficacy of these new agents in terms of CVD outcomes and pancreatitis are warranted 4, 5.