Dr. Kumar’s Take:
This large review study looked at over 53,000 patients to see if fibrates—older cholesterol medications—still offer heart protection. The results were mixed. Fibrates have historically been used for lowering high triglycerides. In this review, they reduced heart attacks and related events, but only in studies where they also lowered LDL cholesterol. Lowering triglycerides alone didn’t seem to reduce heart risk.
In today’s world where many people are already on statins, fibrates may offer little extra benefit unless they’re clearly improving LDL levels. This doesn’t mean fibrates are useless—but they might be most helpful in specific cases where LDL is still high, statins aren’t tolerated, and patient’s are at high risk for heart disease.
Key Takeaways:
- Fibrates reduced heart risk only when LDL cholesterol was lowered.
- Triglyceride reduction alone didn’t reduce heart attacks or strokes.
- The absolute benefit was modest: 2.4% fewer events over an average of 5 years (NNT ~42). That’s about a 0.48% absolute risk reduction per year. (I calculated these numbers from the data in the paper)
- In people already on statins with well-controlled LDL, fibrates offered little added benefit.
- Fibrates may still help people with high LDL or those who can’t take statins.
Brief Summary:
A meta-analysis of 12 randomized trials (totaling 53,231 patients) evaluated the impact of fibrate therapy on heart outcomes. The main goal was to see if fibrates reduced major adverse cardiovascular events (MACE), including heart attack, stroke, cardiovascular death, and need for heart procedures.
Fibrates showed a 13% relative risk reduction in MACE compared to placebo (RR 0.87, 95% CI 0.81–0.94). That translates to an absolute risk reduction of 2.4% over several years. The number needed to treat (NNT) to prevent one MACE was about 42 patients in an average of 5 years. Importantly, the benefit was closely tied to how much LDL cholesterol dropped, not how much triglycerides dropped.
Study Design:
This was a meta-analysis of 12 randomized controlled trials conducted between 1971 and 2022, including over 53,000 patients. The studies compared fibrate drugs (like gemfibrozil, fenofibrate, and others) to placebo, and tracked cardiovascular events.
Researchers also looked at how lipid levels changed with treatment. A special analysis (called meta-regression) was used to see if lowering LDL or triglycerides made a difference in outcomes.
Results:
- Major adverse cardiovascular events (MACE) occurred in 10.6% of patients on fibrates vs. 13.0% on placebo — an absolute risk reduction of 2.4%.
- Relative risk of Major adverse cardiovascular events (MACE) was 0.87, meaning a 13% lower risk on fibrates.
- Number needed to treat (NNT) = 42 patients over about 5 years to prevent one MACE.
- Each 1 mmol/L drop in LDL-C was linked to a 29% lower risk of MACE
- Triglyceride reduction had no clear link to fewer events
- Fibrates didn’t reduce cardiovascular deaths or overall mortality.
Why the Mixed Results?
Earlier studies (from the 1970s–1990s) showed bigger LDL reductions and better outcomes. More recent trials—often done in people already on statins—showed little to no added benefit.
This suggests fibrates may help only when LDL is still a problem, or when used alone in statin-intolerant patients.
The lack of benefit from triglyceride-lowering challenges older thinking. It raises questions about whether triglycerides are a reliable target for reducing cardiovascular risk—at least with current medications.
Related Studies and Research
Red Yeast Rice and Metabolic Syndrome – Investigates how red yeast rice affects lipid levels and metabolic markers in people with metabolic syndrome.
Plant Sterols, Cholesterol, and Heart Health – Reviews how plant sterols impact cholesterol levels and their potential role in heart disease prevention.
Ezetimibe and Heart Disease: A Review – Examines how ezetimibe lowers LDL cholesterol and its effect on cardiovascular outcomes.
Fiber and Heart Disease Risk – Analyzes the role of dietary fiber in cardiovascular health and cholesterol reduction.
TG/HDL-C Ratio and Cardiovascular Risk – Explores the clinical importance of the triglyceride-to-HDL ratio in metabolic and cardiovascular risk.
LDL-C and Mortality: A Review – Investigates how LDL cholesterol levels correlate with mortality risk.
Frequently Asked Questions
Do fibrates help if I’m already on a statin?
Probably not, unless your LDL cholesterol is still high or you can’t tolerate statins. This study showed that benefits were tied to LDL lowering, not just being on fibrates.
What are the main fibrates used?
Common ones include gemfibrozil, fenofibrate, bezafibrate, and pemafibrate. They are mostly used to lower triglycerides and modestly reduce LDL.
Are fibrates safe?
Generally yes, but side effects can include muscle pain, liver enzyme changes, and—rarely—kidney issues. Always discuss with your healthcare provider.
Should I take a fibrate to lower my triglycerides?
Lowering triglycerides might help with pancreatitis risk, especially if levels are very high. But for heart disease risk, lowering LDL seems more important.
Conclusion
Fibrates may still have a role in heart health—especially in people with elevated LDL or who don’t tolerate statins. But their benefits appear to come from lowering LDL, not just reducing triglycerides.
If you’re considering a fibrate, make sure it’s part of a larger plan that addresses LDL cholesterol, lifestyle, and other risk factors. The overall benefit is modest—but for the right person, it may still be meaningful.