NIHR Signal Alternative drug may prevent atrial fibrillation following heart surgery

Published on 12 December 2017

After heart surgery around a third of people have atrial fibrillation, an abnormal heart rhythm, which impedes their recovery and lengthens hospital stay. Colchicine treatment could reduce this complication by about a third.

About 11 people would need this treatment to prevent one of them developing atrial fibrillation. Using amiodarone, an alternative drug commonly used in this situation, other research shows that about seven people would be treated to prevent one person suffering fibrillation.

Colchicine is a drug licensed for the treatment of gout that combines both anti-inflammatory and heart rate control properties. As an older drug, it might be a cheaper alternative and could be safer.

Further study needs to clarify which patient groups could benefit from colchicine, how it compares against current treatments and which dose strikes the best balance between efficacy and side effects.

Alternative drug may prevent atrial fibrillation following heart surgery

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Why was this study needed?

Atrial fibrillation is common following heart surgery, affecting approximately 25-40% of people having coronary artery bypass surgery, and 50-60% of people requiring valve surgery. Untreated, it increases the risk of complications such as stroke and mortality. Substantial healthcare resources are devoted to detection and treatment of the condition.

Post-operative atrial fibrillation is thought to be partly due to inflammation of the heart muscle. Colchicine is a powerful anti-inflammatory possibly with additional effects which may suppress abnormal heart rhythms and has been suggested as a potential option by recent US guidelines. However, it is associated with gastrointestinal side effects.

Previous meta-analyses have given mixed results, probably because they have investigated different procedures, outcomes and assessment times. This study aimed to clarify the effects of colchicine by focusing on one outcome in one timeframe – atrial fibrillation occurring soon after open heart surgery.

What did this study do?

This systematic review and meta-analyses included five randomised controlled trials comparing colchicine with placebo or no treatment in 1,412 patients having coronary artery bypass graft or valve surgery. Two studies came from Italy and one each from Iran, Jordan and Brazil.

All studies used the same colchicine maintenance dose of 0.5mg twice daily, but differed regarding starting dose, start time (three days before to three days after surgery) and duration of use (one week to one month). Atrial fibrillation was assessed until the point of discharge in three studies and up to three months in one study. Authors used a statistical approach to account for these differences.

Three studies had a possible bias because the method of group allocation was unclear and the participants and assessors were aware of the treatment.

What did it find?

  • Colchicine reduced the incidence of atrial fibrillation early after cardiac surgery by 30% compared with placebo or usual care (18% vs 27%, relative risk [RR] 0.69, 95% confidence interval [CI] 0.57 to 0.84). The direction of results was similar across all five studies giving confidence in the pooled finding.
  • Based on four trials (1,196 people), colchicine increased the risk of any adverse drug related-effect by more than two-fold compared with control (21% vs 8.2%, RR 2.53, 95% CI 1.62 to 3.93). Consistent with known side effects, this was mostly gastrointestinal intolerance.
  • There was no evidence that colchicine influenced the risk of major adverse events of death or stroke (3.2% of each group, RR 0.96, 95% CI 0.48 to 1.95; four studies).
  • Colchicine decreased the length of stay by 1.2 days (95% CI -1.89 to -0.44 days; three studies).

What does current guidance say on this issue?

NICE (2014) recommends that patients having heart surgery are offered drug treatment with amiodarone, a beta-blocker or calcium-channel blocker to reduce the risk of atrial fibrillation developing.

The European Society of Cardiology guideline for the management of atrial fibrillation primarily recommends beta blockers to prevent post-operative atrial fibrillation, though amiodarone is listed as another option.

Neither guideline gives any recommendation on the use of colchicine. The European Society of Cardiology mentions that small trials have investigated its use but did not demonstrate clear benefits.

Patients who develop atrial fibrillation require anticoagulation and rate control, with treatment to convert any abnormal rhythm to a normal rhythm if they are symptomatic.

What are the implications?

Colchicine may be an alternative option to prevent post-operative atrial fibrillation.

However, there is still a limited body of evidence and some unanswered questions, particularly how it compares in effect or risk profile with other recommended drugs. The specific populations that might benefit most from colchicine need to be identified.

The optimal dosing or duration of use is also unclear. Minimising side effects would vastly improve the desirability of colchicine for widespread use. Past research suggested a reduced dosage may achieve this without compromising efficacy, but this needs further investigation.

Ongoing studies may give a better indication of its possible place in care.

Citation and Funding

Lennerz C, Barman M, Tantawy M, et al. Colchicine for primary prevention of atrial fibrillation after open-heart surgery: Systematic review and meta-analysis. International Journal of Cardiology. 2017;249:127-37.

No funding information was provided for this study.

Bibliography

NHS Choices. Atrial Fibrillation. London: Department of Health; updated 2015.

NHS Choices. Atrial Fibrillation: Treatment. London: Department of Health; updated 2015.

NICE. Atrial Fibrillation: Management. CG180. London: National Institute for Health and Care Excellence; 2014.

The American Association for Thoracic Surgery. Guidelines for the prevention and management of perioperative trial fibrillation and flutter for thoracic surgical procedures. The Journal of Thoracic and Cardiovascular Surgery. 2014;148(3):e153-93.

The Task Force for the management of atrial fibrillation of the European Society of Cardiology (ESC). 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS. European Heart Journal. 2016;37(38):2893-962.

The Atrial Fibrillation Association. AF Association patient information factsheets. Chipping Norton: The Atrial Fibrillation Association; 2017.

Why was this study needed?

Atrial fibrillation is common following heart surgery, affecting approximately 25-40% of people having coronary artery bypass surgery, and 50-60% of people requiring valve surgery. Untreated, it increases the risk of complications such as stroke and mortality. Substantial healthcare resources are devoted to detection and treatment of the condition.

Post-operative atrial fibrillation is thought to be partly due to inflammation of the heart muscle. Colchicine is a powerful anti-inflammatory possibly with additional effects which may suppress abnormal heart rhythms and has been suggested as a potential option by recent US guidelines. However, it is associated with gastrointestinal side effects.

Previous meta-analyses have given mixed results, probably because they have investigated different procedures, outcomes and assessment times. This study aimed to clarify the effects of colchicine by focusing on one outcome in one timeframe – atrial fibrillation occurring soon after open heart surgery.

What did this study do?

This systematic review and meta-analyses included five randomised controlled trials comparing colchicine with placebo or no treatment in 1,412 patients having coronary artery bypass graft or valve surgery. Two studies came from Italy and one each from Iran, Jordan and Brazil.

All studies used the same colchicine maintenance dose of 0.5mg twice daily, but differed regarding starting dose, start time (three days before to three days after surgery) and duration of use (one week to one month). Atrial fibrillation was assessed until the point of discharge in three studies and up to three months in one study. Authors used a statistical approach to account for these differences.

Three studies had a possible bias because the method of group allocation was unclear and the participants and assessors were aware of the treatment.

What did it find?

  • Colchicine reduced the incidence of atrial fibrillation early after cardiac surgery by 30% compared with placebo or usual care (18% vs 27%, relative risk [RR] 0.69, 95% confidence interval [CI] 0.57 to 0.84). The direction of results was similar across all five studies giving confidence in the pooled finding.
  • Based on four trials (1,196 people), colchicine increased the risk of any adverse drug related-effect by more than two-fold compared with control (21% vs 8.2%, RR 2.53, 95% CI 1.62 to 3.93). Consistent with known side effects, this was mostly gastrointestinal intolerance.
  • There was no evidence that colchicine influenced the risk of major adverse events of death or stroke (3.2% of each group, RR 0.96, 95% CI 0.48 to 1.95; four studies).
  • Colchicine decreased the length of stay by 1.2 days (95% CI -1.89 to -0.44 days; three studies).

What does current guidance say on this issue?

NICE (2014) recommends that patients having heart surgery are offered drug treatment with amiodarone, a beta-blocker or calcium-channel blocker to reduce the risk of atrial fibrillation developing.

The European Society of Cardiology guideline for the management of atrial fibrillation primarily recommends beta blockers to prevent post-operative atrial fibrillation, though amiodarone is listed as another option.

Neither guideline gives any recommendation on the use of colchicine. The European Society of Cardiology mentions that small trials have investigated its use but did not demonstrate clear benefits.

Patients who develop atrial fibrillation require anticoagulation and rate control, with treatment to convert any abnormal rhythm to a normal rhythm if they are symptomatic.

What are the implications?

Colchicine may be an alternative option to prevent post-operative atrial fibrillation.

However, there is still a limited body of evidence and some unanswered questions, particularly how it compares in effect or risk profile with other recommended drugs. The specific populations that might benefit most from colchicine need to be identified.

The optimal dosing or duration of use is also unclear. Minimising side effects would vastly improve the desirability of colchicine for widespread use. Past research suggested a reduced dosage may achieve this without compromising efficacy, but this needs further investigation.

Ongoing studies may give a better indication of its possible place in care.

Citation and Funding

Lennerz C, Barman M, Tantawy M, et al. Colchicine for primary prevention of atrial fibrillation after open-heart surgery: Systematic review and meta-analysis. International Journal of Cardiology. 2017;249:127-37.

No funding information was provided for this study.

Bibliography

NHS Choices. Atrial Fibrillation. London: Department of Health; updated 2015.

NHS Choices. Atrial Fibrillation: Treatment. London: Department of Health; updated 2015.

NICE. Atrial Fibrillation: Management. CG180. London: National Institute for Health and Care Excellence; 2014.

The American Association for Thoracic Surgery. Guidelines for the prevention and management of perioperative trial fibrillation and flutter for thoracic surgical procedures. The Journal of Thoracic and Cardiovascular Surgery. 2014;148(3):e153-93.

The Task Force for the management of atrial fibrillation of the European Society of Cardiology (ESC). 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS. European Heart Journal. 2016;37(38):2893-962.

The Atrial Fibrillation Association. AF Association patient information factsheets. Chipping Norton: The Atrial Fibrillation Association; 2017.

Colchicine for primary prevention of atrial fibrillation after open-heart surgery: Systematic review and meta-analysis

Published on 19 September 2017

Lennerz, C.,Barman, M.,Tantawy, M.,Sopher, M.,Whittaker, P.

Int J Cardiol , 2017

BACKGROUND: Atrial fibrillation occurs frequently after open-heart surgery. It is associated with increased morbidity and mortality, longer hospital stays, and increased healthcare costs. Prophylactic administration of colchicine may mitigate post-operative atrial fibrillation (POAF). METHODS: We searched PubMed, ClinicalTrials.gov and CENTRAL databases to identify randomized controlled trials (RCTs) that; (1) compared prophylactic use of colchicine to placebo, or usual care, in patients with sinus rhythm who underwent elective open-heart surgery and (2) reported POAF-incidence. We excluded trials focused on incidence of atrial fibrillation after percutaneous interventions or colchicine treatment of diagnosed pericarditis or post-pericardiotomy-syndrome. A random-effects model was used to pool data for POAF-incidence as the primary outcome and for drug-related adverse effects, major adverse events (death and stroke), and hospital length-of-stay as secondary outcomes. RESULTS: We included five RCTs (1412 patients). Colchicine treatment reduced POAF-events by 30% versus placebo or usual care (18% vs. 27%, risk ratio (RR) 0.69, 95% confidence interval (CI) 0.57 to 0.84, p=0.0002). Adverse drug-related effects, especially gastrointestinal intolerance, increased with colchicine; (21% vs. 8.2%, RR 2.52, 95% CI 1.62 to 3.93, p<0.0001). However, major adverse events were unchanged (3.2% vs. 3.2%, RR 0.96, 95% CI 0.48 to 1.95, p=0.92). Length-of-stay decreased by 1.2days with colchicine (95% CI -1.89 to -0.44, p=0.002). CONCLUSION: Colchicine demonstrated superior efficacy versus usual care for prevention of atrial fibrillation after cardiac surgery. Moreover, colchicine treatment was associated with shorter hospital stays. These benefits outweigh increased risk of adverse drug-related effects; although further work is needed to minimize gastrointestinal effects.

Expert commentary

Atrial fibrillation is a common clinical problem, associated with increased risk of stroke. It is particularly common after cardiac surgery and is often treated with potentially toxic drugs such as amiodarone.

Colchicine is an old drug, commonly used for gout and less commonly for pericarditis. It appears to be safe with a moderate side effect burden. This systematic review suggests that colchicine could be a cheap and effective way of reducing postoperative atrial fibrillation.

This use of an old drug deserves wider consideration.

Dr Alice Wood, Cardiology Registrar, Glenfield Hospital, Leicester