#97 Fibrates: Statin’s Trusty Sidekick or Lackluster Fallback?
CLINICAL QUESTION
Do fibrates reduce cardiovascular (CV) events?
BOTTOM LINE
When used alone, fibrates reduce non-fatal coronary events, but have no effect on mortality or other CV events, including stroke. Current evidence suggests fibrates provide no advantage when added to statin therapy.
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EVIDENCE
At least ten systematic reviews evaluate fibrates on CV disease with similar findings.1-10 Focusing on the most up-to-date and complete:
- Meta-analysis1 of 18 trials (45,058 patients) of fibrates versus placebo over one to six years:
- 10% (confidence interval 0-18%) relative risk reduction (RRR) in CV events.
- Primarily due to a 19% RRR in non-fatal coronary events.
- No significant effect on all-cause mortality, vascular mortality or stroke.
- Coronary benefits seen in both primary and secondary prevention trials.
- 10% (confidence interval 0-18%) relative risk reduction (RRR) in CV events.
- Only one trial (ACCORD11) evaluated a fibrate or placebo added to statin therapy:
- No statistically significant difference in cardiovascular events over 4.7 years.
- Fenofibrate 10.5%, placebo 11.3% (p=0.32).
- No statistically significant difference in cardiovascular events over 4.7 years.
- The latest Canadian dyslipidemia guidelines12 recommend against routine use of fibrates in patients taking statins.
- Before initiating a fibrate, consider optimizing other CV interventions that provide a better value, for example:
- In a primary prevention patient with 10% risk of CV disease over 10 years:
- Fibrates reduce CV risk to 9%;1
- Statins reduce CV risk to 7.5%;13
- Thiazides reduce CV risk to 7%.14
- Whereas fibrate benefits are limited to non-fatal coronary events, statins and thiazides also reduce stroke and mortality risk.
- In a primary prevention patient with 10% risk of CV disease over 10 years:
- Theoretically fibrates could reduce the risk of pancreatitis (by reducing triglycerides). The best evidence15 suggests they do the opposite:
- Fibrates increase pancreatitis (Number Needed to Harm (NNH)=935) at five years.
- Statins reduce pancreatitis (Number Needed to Treat (NNT)=1200) at five years.
- Additional potential adverse effects associated with fibrates include:
- Venous thromboembolism (NNH ~110)16 over five years;
- Acute kidney injury (NNH ~450)17 during first three months of initiation;
- Rhabdomyolysis over five years for fibrates (NNH ~5050) and for fibrates with statins (NNH ~1975).18
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