CertMedEd – Colchicine and Cardiac Surgery Patients

CertMedEd – Colchicine and Cardiac Surgery Patients

Postpericardiotomy syndrome (the episode of symptoms of pericarditis, including chest pain), postoperative atrial fibrillation (AF), and postoperative pericardial/pleural effusions (excess fluid around the heart and lungs) are all complications that can arise post-cardiac surgery. These complications affect more than one third of patients and, as a result, may be responsible for increased morbidity, extended hospital stay, lead to hospital readmissions and often a need for invasive treatments.

In one trial, according to the paper, use of colchicine assisted in the prevention of the above complications.

Colchicum
Colchicine is derived from the meadow saffron or autumn crocus plant.

 

Colchicine is a highly toxic plant hormone that is utilized medically in the treatment of gout. Colchicine is derived from the meadow saffron or autumn crocus plant, which is plentiful in meadows in Europe and has become naturalized in parts of North America. It is produced in tablets, granules, and ampoules of sterile solution.

The objective of the study was to determine the effectiveness and safety of using oral colchicine to reduce complications after cardiac surgery.

Dr. Massimo Imazio, of Maria Vittoria Hospital, Torino, Italy, and colleagues randomly assigned 360 cardiac surgery patients, enrolled in 11 centers in Italy, to two groups. The patients received either placebo or colchicine starting between 48 and 72 hours before surgery, and continued for 1 month after surgery. Centers were encouraged to use continuous electrocardiographic (ECG) monitoring for at least 5 days after surgery.

Patients received follow-up involving physical examination, blood chemistry, ECG, echocardiography aimed at identification and assessment of pericardial effusion, and thoracic ultrasound at 1 day, 3 days, day of discharge after surgery, weekly during the rehabilitation phase, then at 1 month and 3 months. At least one chest X-ray was performed during the hospital stay and then as clinically indicated.

Use of colchicine ‘significantly reduced incidence of postpericardiotomy syndrome’

The main outcomes of the study are as follows:

Colchicine group

  • Postpericardiotomy occurred in 35 of 180 patients (19.4%)
  • Postoperative AF occurred in 61 of 180 patients (33.9%)
  • Postoperative pericardial/pleural effusions occurred in 103 of 180 patients (57.2%)
  • Adverse event rates occurred in 36 of 180 patients (20.0%).

Placebo group

  • Postpericardiotomy occurred in 53 of 180 patients (29.4%)
  • Postoperative AF occurred in 75 of 180 patients (41.7%)
  • Postoperative pericardial/pleural effusions occurred in 106 of 180 patients (58.9%)
  • Adverse event rates occurred in 21 of 180 patients (11.7%).

The authors write:

“In this multicenter trial, perioperative administration of colchicine significantly reduced the incidence of postpericardiotomy syndrome after cardiac surgery but did not reduce the risk of postoperative AF and postoperative pericardial/pleural effusions by intention-to-treat analysis.”

They add, “About 20% of all patients enrolled in the trial discontinued study drug; this relatively high rate may have affected the overall efficacy of the drug, especially for postoperative AF prevention.”

The study, released early online to coincide with its presentation at the European Society of Cardiology Congress, highlights that adverse event rates occurred primarily due to increased incidence of gastrointestinal intolerance, 14.4% in the colchicine group and 6.7% in the placebo group. No serious adverse events were observed.

“The high rate of adverse effects is a reason for concern and suggests that colchicine should be considered only in well-selected patients,” the researchers conclude.

 

Click here to read the entire JAMA Article (Abstract is listed for you below)

Colchicine for Prevention of Postpericardiotomy Syndrome and Postoperative Atrial Fibrillation: The COPPS-2 Randomized Clinical Trial”

Abstract

Importance  Postpericardiotomy syndrome, postoperative atrial fibrillation (AF), and postoperative effusions may be responsible for increased morbidity and health care costs after cardiac surgery. Postoperative use of colchicine prevented these complications in a single trial.

Objective  To determine the efficacy and safety of perioperative use of oral colchicine in reducing postpericardiotomy syndrome, postoperative AF, and postoperative pericardial or pleural effusions.

Design, Setting, and Participants  Investigator-initiated, double-blind, placebo-controlled, randomized clinical trial among 360 consecutive candidates for cardiac surgery enrolled in 11 Italian centers between March 2012 and March 2014. At enrollment, mean age of the trial participants was 67.5 years (SD, 10.6 years), 69% were men, and 36% had planned valvular surgery. Main exclusion criteria were absence of sinus rhythm at enrollment, cardiac transplantation, and contraindications to colchicine.

Interventions  Patients were randomized to receive placebo (n=180) or colchicine (0.5 mg twice daily in patients ≥70 kg or 0.5 mg once daily in patients <70 kg; n=180) starting between 48 and 72 hours before surgery and continued for 1 month after surgery.

Main Outcomes and Measures  Occurrence of postpericardiotomy syndrome within 3 months; main secondary study end points were postoperative AF and pericardial or pleural effusion.

Results  The primary end point of postpericardiotomy syndrome occurred in 35 patients (19.4%) assigned to colchicine and in 53 (29.4%) assigned to placebo (absolute difference, 10.0%; 95% CI, 1.1%-18.7%; number needed to treat = 10). There were no significant differences between the colchicine and placebo groups for the secondary end points of postoperative AF (colchicine, 61 patients [33.9%]; placebo, 75 patients [41.7%]; absolute difference, 7.8%; 95% CI, −2.2% to 17.6%) or postoperative pericardial/pleural effusion (colchicine, 103 patients [57.2%]; placebo, 106 patients [58.9%]; absolute difference, 1.7%; 95% CI, −8.5% to 11.7%), although there was a reduction in postoperative AF in the prespecified on-treatment analysis (placebo, 61/148 patients [41.2%]; colchicine, 38/141 patients [27.0%]; absolute difference, 14.2%; 95% CI, 3.3%-24.7%). Adverse events occurred in 21 patients (11.7%) in the placebo group vs 36 (20.0%) in the colchicine group (absolute difference, 8.3%; 95% CI; 0.76%-15.9%; number needed to harm = 12), but discontinuation rates were similar. No serious adverse events were observed.

Conclusions and Relevance  Among patients undergoing cardiac surgery, perioperative use of colchicine compared with placebo reduced the incidence of postpericardiotomy syndrome but not of postoperative AF or postoperative pericardial/pleural effusion. The increased risk of gastrointestinal adverse effects reduced the potential benefits of colchicine in this setting.

Trial Registration  clinicaltrials.gov Identifier: NCT01552187




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