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#299 Cardiovascular prevention trials: Now calling colchicine to the stand


CLINICAL QUESTION
Is colchicine effective for secondary cardiovascular prevention?

BOTTOM LINE
Daily low-dose colchicine in people with coronary artery disease (CAD) lowers the risk of cardiovascular events by ~1%/year (relative risk reduction 25-30%), but increases the risk of gastrointestinal events (mostly diarrhea) by ~2% and has no effect on mortality.


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EVIDENCE
  • At least 7 systematic reviews compared the effect of colchicine to placebo in addition to standard therapy in individuals with CAD [4-11 randomized controlled trials (RCTs), 5820-12869 participants, duration 5 days to 3 years].1-7
    • All showed similar:
      • Colchicine reduced cardiovascular events [relative risk reduction (RRR) ~30%].
      • No difference in mortality.
    • Most meta-analyses evaluating gastrointestinal events found ~2% absolute risk with colchicine (mostly diarrhea).2,3,6
  • Two largest placebo-controlled, good quality RCTs, non-industry funded:
    • LoDoCo2 trial8 compared colchicine 0.5mg daily versus placebo for 2.5 years in 5522 participants (age≈66, 15% female) with stable CAD.
      • Cardiovascular events (cardiovascular mortality, myocardial infarction, ischemic strokes, urgent revascularization): Colchicine 6.8% versus 9.6% placebo, RRR=29%, number needed to treat (NNT)=36.
      • No significant difference in mortality (2.6% versus 2.2%).
      • No difference in adverse events except myalgias (NNH=38).
    • COLCOT trial9 compared colchicine 0.5mg daily versus placebo for 23 months in 4745 participants (age≈61, 19% female) within 1 month after myocardial infarction.
      • Cardiovascular events (cardiovascular mortality, myocardial infarction, strokes, urgent revascularization): Colchicine 5.5% versus 7.1% placebo, RRR=24%, NNT=63.
      • No difference in mortality (1.8% in both groups).
      • No difference in any or serious adverse events.
  • Limitations: Excluded individuals with various risk factors for colchicine toxicity (examples kidney or muscular disease) and one trial8 had an open-label colchicine run-in period that excluded 15% of patients before randomization, mostly because of adverse events.
Context
  • Recent guidelines for secondary prevention in CAD or post-myocardial infarction do not make any recommendations about colchicine.10,11
  • The new 0.5mg dose costs ~$45 for a 3-month supply (versus $25 for 0.6mg dose).12,13
  • Colchicine efficacy on cardiovascular events better [example ezetimibe (RRR ~6%)] or comparable [example aspirin or statins (RRR~25%)] to other preventive therapies, but without the benefits on mortality of aspirin and statins.14,15 

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Author(s):

  • Nicolas Dugré PharmD MSc BCPAC
  • Ricky D Turgeon BSc (Pharm) ACPR PharmD
  • Stéphane Vanier MD CCFP

1. Xia M, Yang X, Qian C. Am J Cardio. 2021; 140:33-38.

2. Ullah W, Gowda SN, Fischman D. Cardiovasc Revasc Med. 2021; 23:1-6.

3. Xiang Z, Yang J, Yang J, et al. Intern Emerg Med. 2021; 16(2):487-496.

4. Samuel M, Tardif JC, Bouabdallaoui N, et al. Can J Cardiol. 2021; 37(5):776-785.

5. Fiolet AT, Opstal TS, Mosterd A, et al. Eur Heart J. 2021; ehab115.

6. Andreis A, Imazio M, Piroli F, et al. Eur J Prev Cardiol. 2021; zwab045.

7. Al-Abdouh A, Barbarawi M, Khan SU, et al. Coron Artery Dis. 2020 Jul 23. doi:10.1097/MCA.0000000000000931. Online ahead of print.

8. Nidorf SM, Fiolet AT, Mosterd A, et al. N Engl J Med. 2020; 383:1838-1847.

9. Tardif JC, Kouz S, Waters DD, et al. N Engl J Med. 2019; 381:2497-2505.

10. Knuuti J, Wijns W, Saraste A, et al. Eur Heart J. 2020; 41:407-77.

11. Collet JP, Thiele H, Barbato E, et al. Eur Heart J. 2021; 42:1289-367.

12. Interactive Drug Benefit List [website]. Edmonton, AB: Government of Alberta; 2021. Available from: https://idbl.ab.bluecross.ca/idbl/load.do. Accessed 2021 July 08.

13. PharmaClik. McKesson Canada. 2021. https://clients.mckesson.ca/ Accessed September 27, 2021.

14. Koskinas KC, Siontis GC, Piccolo R, et al. Eur Heart J. 2018; 39(14):1172-80.

15. Antithrombotic Trialists' Collaboration. BMJ. 2002; 324(7329):71.

Authors do not have any conflicts of interest to declare.