Statin Therapy is Recommended for ASCVD Risk of 10.5%, but Fibrate Addition is Not Recommended
For a person with an ASCVD risk of 10.5%, statin therapy alone is recommended, and the addition of a fibrate is generally not recommended due to lack of proven cardiovascular benefit and increased risk of adverse effects. 1
Statin Recommendation for ASCVD Risk of 10.5%
- An ASCVD risk of 10.5% exceeds the 7.5% threshold established by the ACC/AHA guidelines, making this patient a clear candidate for moderate to high-intensity statin therapy 1
- The ACC/AHA guidelines provide strong evidence that statin therapy offers a net benefit for individuals with ≥7.5% 10-year ASCVD risk, with the absolute benefit in ASCVD risk reduction proportional to baseline risk 1
- For patients with 10-year ASCVD risk >7.5%, the number needed to treat (NNT) with moderate-intensity statin therapy (36-44) clearly outweighs the number needed to harm (NNH) (100) for diabetes development 1
Why Fibrate Addition is Not Recommended
- Statin plus fibrate combination therapy has not been shown to improve ASCVD outcomes and is generally not recommended 1
- The ACCORD study in patients with type 2 diabetes found that adding fenofibrate to simvastatin did not reduce the rate of cardiovascular events compared to simvastatin alone 1
- The FDA label for fenofibrate notes that in the ACCORD Lipid trial, fenofibrate plus statin combination therapy showed a non-significant 8% relative risk reduction in major adverse cardiovascular events compared to statin monotherapy 2
- The FIRST trial demonstrated that adding fenofibric acid to atorvastatin did not further decrease carotid intima-media thickness progression in high-risk patients with mixed dyslipidemia 3
Safety Concerns with Statin-Fibrate Combination
- Combination therapy with statins and fibrates is associated with an increased risk for abnormal liver enzymes, myositis, and rhabdomyolysis 1
- The risk of rhabdomyolysis is more common with higher doses of statins, renal insufficiency, and appears to be higher when statins are combined with gemfibrozil compared to fenofibrate 1
- In the FIRST trial, fenofibric acid plus atorvastatin was associated with a greater incidence of renal-related adverse events compared with atorvastatin monotherapy (6.5% versus 0.9%) 3
Appropriate Statin Therapy Approach
- For a patient with 10.5% ASCVD risk, moderate to high-intensity statin therapy should be initiated with the goal of reducing LDL-C by 30-49% (moderate intensity) or ≥50% (high intensity) 1
- Before initiating statin therapy, a clinician-patient discussion should include consideration of potential ASCVD risk-reduction benefits, adverse effects, drug-drug interactions, and patient preferences 1
- Monitor lipid levels to ensure adherence, therapeutic response, and safety 1
Special Considerations
- If the patient has elevated triglycerides (≥500 mg/dL), treatment with a fibrate alone may be considered to reduce the risk of pancreatitis, but not in combination with a statin 1
- For patients with controlled LDL-C on a statin but elevated triglycerides (135-499 mg/dL), icosapent ethyl may be considered instead of a fibrate to reduce cardiovascular risk 1
- The Cochrane review found that fibrates may lower the risk for cardiovascular events in primary prevention, but the absolute treatment effects are modest (absolute risk reductions <1%) 4
Monitoring and Follow-up
- Monitor for statin-associated side effects including myopathy (0.01 excess cases per 100) and new-onset diabetes (0.1-0.3 excess cases per 100 per year depending on statin intensity) 1
- Assess lipid response 4-12 weeks after initiating statin therapy to evaluate adherence and efficacy 1
- Consider intensifying statin therapy if LDL-C goals are not achieved before considering addition of other agents 5