Circ: Colchicine reduces incidence of AF after cardiac surgery
Colchicine treatment started on day three after cardiac surgery reduced the incidence of post-operative atrial fibrillation (POAF) without significant side effects, according to a study published online Nov. 16 in Circulation. Compared with placebo, colchicine also trimmed patients’ hospital and rehabilitation stays, making treatment a potentially a cost-saving approach for managing patients.
The Colchicine for the Prevention of the Post-Pericardiotomy Syndrome (COPPS) study, a prospective, randomized, double-blind, placebo-controlled multicenter trial, found that colchicine was safe and efficacious for preventing post-pericardiotomy syndrome (PPS), with about a 12 percentage point reduction in the incidence of PPS. Massimo Imazio, MD, of the Department of Cardiology at Maria Vittoria Hospital in Torino, Italy, and colleagues postulated that the anti-inflammatory properties of colchicine might make it a safe and effective treatment for POAF.
In a substudy of COPPS, they enrolled 336 patients in sinus rhythm who were randomized to receive either placebo (167 patients) or colchicine (169 patients). The colchicine group received standard treatment plus, starting on post-operative day three, colchicine at the dosage of 1.0 mg twice daily for the first day followed by a maintenance dosage of 0.5 mg or 0.25 twice daily, depending on the patient’s weight, for one month. The placebo group received standard treatment only.
The primary endpoint was the rate of POAF. AF was defined as no consistent P-waves before each QRS complex and an irregular ventricular rate. The episode had to last five minutes or longer.
The authors found that the addition of colchicine reduced the incidence of POAF and halved the mean duration of POAF. POAF incidence in patients receiving colchicine was 12 percent vs. 22 percent in the placebo group, with a relative risk reduction of 45 percent. The colchicine group had a shorter in-hospital stay (9.4 days vs. 10.3 days), a shorter rehabilitation stay (12.1 days vs. 13.9 days) and a shorter overall hospital stay (21 days vs. 24 days).
The incidence of death and stroke was similar in both groups, and there were no severe side effects, although the colchicine group showed an increased trend toward complications.
Imazio and colleagues wrote that, as in the COPPS trial, colchicine reduced the incidence of POAF without significant side effects. “Moreover, colchicine halved the mean duration of POAF; such an effect may be particularly important for reducing the subsequence rate of late AF (AF after 30 days of surgery) because a longer duration of POAF is a strong and independent predictor of late AF.”
They speculated on the electrophysiological mechanisms for POAF, including pericardial inflammation, autonomic imbalance, excessive catecholamines production and hemodynamic factors. “Both systemic and local inflammatory responses are believed to contribute to the pathogenesis of POAF,” they wrote. “Inflammation, inhomogeneity of atrial conduction, and the incidence of POAF are decreased by corticosteroids. On this basis, colchicine may have the potential to be efficacious in preventing not only PPS but also POAF.”
They concluded that colchicine may provide an inexpensive and safe option for preventing PPS and POAF, potentially reducing costs associated with cardiac surgery. They added that the study was relatively small and that the highest incidence of POAF generally occurs in the first postoperative days.
“Further research should address whether alternative regimens providing the drug in the perioperative period (e.g., starting the administration before the operation) may provide better prevention for either PPS or POAF,” they suggested. “Both efficacy and safety should be evaluated in this setting.”
David R. Van Wagoner, PhD, of the Department of Molecular Cardiology and Cardiovascular Medicine at the Cleveland Clinic, agreed in an accompanying editorial that colchicine should be studied to “evaluate the utility of perioperative colchicine treatment (beginning at the time of surgery or before) as a prophylactic approach that can reduce the morbidity associated with this very common postsurgical complication.”
“If colchicine is effective in preventing POAF, this treatment would constitute an important new indication for the use of a very old drug,” he wrote.
The Colchicine for the Prevention of the Post-Pericardiotomy Syndrome (COPPS) study, a prospective, randomized, double-blind, placebo-controlled multicenter trial, found that colchicine was safe and efficacious for preventing post-pericardiotomy syndrome (PPS), with about a 12 percentage point reduction in the incidence of PPS. Massimo Imazio, MD, of the Department of Cardiology at Maria Vittoria Hospital in Torino, Italy, and colleagues postulated that the anti-inflammatory properties of colchicine might make it a safe and effective treatment for POAF.
In a substudy of COPPS, they enrolled 336 patients in sinus rhythm who were randomized to receive either placebo (167 patients) or colchicine (169 patients). The colchicine group received standard treatment plus, starting on post-operative day three, colchicine at the dosage of 1.0 mg twice daily for the first day followed by a maintenance dosage of 0.5 mg or 0.25 twice daily, depending on the patient’s weight, for one month. The placebo group received standard treatment only.
The primary endpoint was the rate of POAF. AF was defined as no consistent P-waves before each QRS complex and an irregular ventricular rate. The episode had to last five minutes or longer.
The authors found that the addition of colchicine reduced the incidence of POAF and halved the mean duration of POAF. POAF incidence in patients receiving colchicine was 12 percent vs. 22 percent in the placebo group, with a relative risk reduction of 45 percent. The colchicine group had a shorter in-hospital stay (9.4 days vs. 10.3 days), a shorter rehabilitation stay (12.1 days vs. 13.9 days) and a shorter overall hospital stay (21 days vs. 24 days).
The incidence of death and stroke was similar in both groups, and there were no severe side effects, although the colchicine group showed an increased trend toward complications.
Imazio and colleagues wrote that, as in the COPPS trial, colchicine reduced the incidence of POAF without significant side effects. “Moreover, colchicine halved the mean duration of POAF; such an effect may be particularly important for reducing the subsequence rate of late AF (AF after 30 days of surgery) because a longer duration of POAF is a strong and independent predictor of late AF.”
They speculated on the electrophysiological mechanisms for POAF, including pericardial inflammation, autonomic imbalance, excessive catecholamines production and hemodynamic factors. “Both systemic and local inflammatory responses are believed to contribute to the pathogenesis of POAF,” they wrote. “Inflammation, inhomogeneity of atrial conduction, and the incidence of POAF are decreased by corticosteroids. On this basis, colchicine may have the potential to be efficacious in preventing not only PPS but also POAF.”
They concluded that colchicine may provide an inexpensive and safe option for preventing PPS and POAF, potentially reducing costs associated with cardiac surgery. They added that the study was relatively small and that the highest incidence of POAF generally occurs in the first postoperative days.
“Further research should address whether alternative regimens providing the drug in the perioperative period (e.g., starting the administration before the operation) may provide better prevention for either PPS or POAF,” they suggested. “Both efficacy and safety should be evaluated in this setting.”
David R. Van Wagoner, PhD, of the Department of Molecular Cardiology and Cardiovascular Medicine at the Cleveland Clinic, agreed in an accompanying editorial that colchicine should be studied to “evaluate the utility of perioperative colchicine treatment (beginning at the time of surgery or before) as a prophylactic approach that can reduce the morbidity associated with this very common postsurgical complication.”
“If colchicine is effective in preventing POAF, this treatment would constitute an important new indication for the use of a very old drug,” he wrote.