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#97 Fibrates: Statin’s Trusty Sidekick or Lackluster Fallback?


CLINICAL QUESTION
QUESTION CLINIQUE
Do fibrates reduce cardiovascular (CV) events?


BOTTOM LINE
RÉSULTAT FINAL
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
DONNÉES PROBANTES
At least ten systematic reviews evaluate fibrates oCV 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. 
  • Only one trial (ACCORD11) evaluated 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). 
Context:  
  • 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. 
  • 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  
updated jan 27 2018 by ricky


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Author(s)
Auteur(s)
  • G. Michael Allan MD CCFP
  • Ricky D. Turgeon BSc(Pharm) ACPR PharmD

1. Jun M, Foote C, Lv J, et al. Lancet. 2010; 375:1875-84.

2. Abourbih S, Filion KB, Joseph L, et al. Am J Med. 2009; 122:962.e1-962.e8.

3. Saha SA, Kizhakepunnur LG, Bahekar A, et al. Am Heart J. 2007; 154:943-53.

4. Robins SJ, Bloomfield HE. Curr Opin Lipidol. 2006 Aug; 17(4):431-9.

5. Loomba RS, Arora R. Am J Ther. 2010 Nov-Dec; 17(6):e182-8.

6. Saha SA, Arora RR. Int J Cardiol. 2010 May 28; 141(2):157-66.

7. Birjmohun RS, Hutten BA, Kastelein JJ, et al. J Am Coll Cardiol 2005; 45:185-97.

8. Studer M, Briel M, Leimenstoll B, et al. Arch Intern Med. 2005; 165:725-730.

9. Wang D, Liu B, Tao W, Hao Z, Liu M. Cochrane Database Syst Rev 2015;10:CD009580.

10. Jakob T, Nordmann AJ, Schandelmaier S, Ferreira-Gonzalez I, Briel M. Cochrane Database Syst Rev 2016;11:CD009753.

11. The ACCORD Study Group. N Engl J Med. 2010; 362:1563-74.

12. Anderson TJ, Gregoire J, Pearson GJ, et al. Can J Cardiol 2016;32:1263-82.

13. Taylor F, Huffman MD, Macedo AF, et al. Cochrane Database Syst Rev. 2013; (3):CD004816.

14. Wright HM, Musini VM. Cochrane Database Syst Rev. 2009; (3):CD001841.

15. Preiss D, Tikkanen MJ, Welsh P, et al. JAMA. 2012; 308:804-11.

16. Squizzato A, Galli M, Romualdi E, et al. Eur Heart J. 2010; 31:1248-56.

17. Zhao YY, Weir MA, Manno M, et al. Ann Intern Med. 2012; 156:560-9.

18. Amend KL, Landon J, Thyagarajan V, et al. Ann Pharmacother. 2011; 45:1230-9.

Authors do not have any conflicts of interest to declare.

Les auteurs n’ont aucun conflit d’intérêts à déclarer.

Most recent review: 27/01/2018

By: Ricky D. Turgeon BSc(Pharm) ACPR PharmD

Comments:

Evidence Updated: No new RCTs, added Cochrane reviews; Bottom Line: Unchanged.

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