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#342 Triglyce-Ride that High?


CLINICAL QUESTION
QUESTION CLINIQUE
Do triglyceride-lowering medications (fibrates, statins, niacin, omega-3s) reduce the risk of pancreatitis in patients with hypertriglyceridemia?


BOTTOM LINE
RÉSULTAT FINAL
No randomized controlled trials (RCTs) have assessed the effect of fibrates or any other triglyceride-lowering medication on pancreatitis risk in patients with “very high” triglycerides (≥5.6 mmol/L). In patients with triglycerides <5.6 mmol/L, fibrates either have no effect on pancreatitis or increase the absolute risk by ~0.1% over 5 years, whereas statins lower the risk by 0.1%.



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EVIDENCE
DONNÉES PROBANTES
  • No RCT examined triglyceride-lowering medications in patients with triglycerides ≥5.6 mmol/L.
  • Systematic review1 of cardiovascular RCTs of fibrates (7 RCTs, 40,162 patients, average baseline triglycerides 1.6-2.1 mmol/L) and statins (21 RCTs, 153,414 patients, average baseline triglycerides 1.3-2.1 mmol/L):
    • Pancreatitis at ~5 years (differences statistically significant):
      • Fibrates: 0.4% versus 0.3% with placebo.
      • Statins: 0.2% versus 0.3% with placebo.
    • Largest RCT2 (not included in above review) compared pemafibrate (not available in Canada) to placebo in 10,497 patients with type 2 diabetes, fasting triglycerides 2.0-5.5 mmol/L (median 3.1 mmol/L), and high-density-lipoprotein cholesterol <1.0 mmol/L. After 3.4 years:
      • Pancreatitis: 0.5% in both groups.
    • No evidence for niacin or omega-3 fatty acids on pancreatitis risk in any triglyceride group

CONTEXT
CONTEXTE
  • Alcohol overuse and gallstones account for the majority of acute pancreatitis,3,4 whereas hypertriglyceridemia account for <5% of cases.4,5
    • Fibrates (except possibly pemafibrate)2 increase risk of developing gallstones by ~1% over 6 years,6-8 potentially explaining how they lead to a net increase in pancreatitis.
  • Guidelines recommend fibrates to lower triglyceride-related pancreatitis risk in patients with “elevated” triglycerides, but differ in threshold triglyceride levels to consider treating (5.6-11.2 mmol/L).9-10
  • In a cohort study of 1.5 million patients, the 5-year risk of acute pancreatitis based on triglyceride concentration ranges:11
    • 4.5-10mmol/L: 0.8%
    • 10-20 mmol/L: 1.5%
    • >20 mmol/L: 3.5%
  • Cardiovascular benefits:
    • Fibrates only reduce non-fatal coronary events (19% relative risk reduction), with no benefit when added to statins.12
    • Statins reduce cardiovascular events (25-35% relative risk reduction) and all-cause mortality (10% relative risk reduction).13


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Author(s)
Auteur(s)
  • Blair J. MacDonald PharmD
  • Scott Garrison MD PhD CCFP
  • Ricky D. Turgeon BSc(Pharm) ACPR PharmD

1. Preiss D, Tikkanen MJ, Welsh P, et al. L JAMA. 2012; 308(8):804-811.

2. Das Pradhan A, Glynn RJ, Fruchart JC, et al. N Engl J Med. 2022; 387(21):1923-1934.

3. Yadav D, Lowenfels AB. Pancreas. 2006 Nov; 33(4):323-305.

4. Hassanloo J, Béland-Bonenfant S, Paquette M, et al. J Clin Lipidol. 2022 Jul-Aug; 16(4):455-62.

5. Tenner S, Baillie J, DeWitt J, et al. Am J Gastroenterol. 2013 Sep; 108(9):1400-15; 1416.

6. Bodmer M, Brauchli YB, Krähenbühl S, et al. JAMA. 2009; 302(18):2001-2007.

7. Caroli-Bosc FX, Le Gall P, Pugliese P, et al. Dig Dis Sci. 2001; 46(3):540-544.

8. Coronary Drug Project Research Group. N Engl J Med. 1977; 296(21):1185-1190.

9. Berglund L, Brunzell JD, Goldberg AC, et al. J Clin Endocrinol Metab. 2012; 97(9):2969-2989.

10. Grundy SM, Stone NJ, Bailey AL, et al. J Am Coll Cardiol. 2019; 73(24):3168-3209.

11. Patel RS, Pasea L, Soran H, et al. Cardiovasc Diabetol. 2022; 21(1):102.

12. Turgeon RD, Allan M. Tools for Practice #97. Available at: https://cfpclearn.ca/tfp97/. Accessed on April 4, 2023.

13. Allan M, Lindblad AJ, Comeau A, et al. Can Fam Physician. 2015 Oct; 61(10):857-67, e439-50.

Authors do not have any conflicts of interest to declare.

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