JACC in a Flash: Colchicine for Post-PVI AFib Recurrence and the HF-ACTION Trial
Anti-Inflammatory Agent Prevents Early AFib Recurrence Post-PVI
Pro-inflammatory processes induced by pulmonary vein isolation (PVI), the mainstay of current atrial fibrillation (AFib) ablation therapy, have been implemented in early AFib recurrence. Although a short course of corticosteroids has been shown to reduce immediate AFib recurrence post-ablation, their unwanted side effects preclude mid- or long-term use in these patients. Spyridon Deftereos, MD, and colleagues report that an anti-inflammatory agent, colchicine, successfully prevents early AFib recurrence, suggesting that the drug be included in the therapeutic management of AFib patients after catheter ablation.
Colchicine, proven to reduce postoperative AFib incidence without serious adverse events in the Colchicine for the Prevention of the Post-pericardiotomy Syndrome (COPPS) study, was selected as an "obvious candidate" for post-ablation AFib recurrence, according to the study authors. Dr. Deftereos, from the department of cardiology at Athens General Hospital in Greece, and investigators conducted a randomized, double-blind, controlled trial comparing the effectiveness of colchicine and placebo in reducing AFib recurrence three months after radiofrequency PVI in patients with paroxysmal AFib. A total of 161 patients completed the study: 81 received treatment with 0.5 mg colchicine twice daily for three months and 80 received placebo. To measure inflammatory reaction, calcium reactive protein (CRP) and IL-6 blood levels were obtained one day after ablation and on day four of treatment.
Twenty-seven (33.5 percent) of the placebo patients experienced a recurrence of AFib, compared with 13 (16 percent) in the colchicine group (p = 0.01; odds ratio [OR] = 0.38; 95 percent CI 0.18-0.80). On average, patients on colchicine remained free from recurrence for a longer period of time: 82.2 days (95 percent CI 77.8-86.7 days) vs. 68.9 days (95 percent CI 61.7-76.1 days). Patients who did experience recurrence in either group tended to be older, have a larger left atrium, and have a higher prevalence of hypertension, the authors noted.
Median levels of inflammatory biomarkers were similar between the two groups immediately after ablation, as the researchers expected, but there was a significant difference on day four, with higher CRP and IL-6 levels in the placebo group. Patients on colchicine did experience a higher rate of gastrointestinal side effects (13.5 vs. 5.1 percent in the placebo group), but no serious adverse events were reported.
In an accompanying editorial, Gregory M. Marcus, MD, MAS, and Jonathan C. Hsu, MD, from University of California, San Francisco, acknowledge that Deftereos et al.'s study "likely provides the strongest evidence to date that inflammation is causal in early-recurrence AF," but also draw attention to a lingering question: "The as-yet unanswered question is whether reduction in early-recurrence AF will translate into long-term success.... Future studies will be important to determine the optimal dose and duration of colchicine, as well as to determine if these early effects lead to lasting success."
- Deftereos S, Giannopoulos G, Kossyvakis C, et al. J Am Coll Cardiol. 2012;60:1790-6.
- Marcus GM, Hsu JC. J Am Coll Cardiol. 2012;60:1797-8.
HF-ACTION: A Dose-Response Relationship Between Exercise and Adverse Event Risk
The Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training (HF-ACTION) trial demonstrated that aerobic exercise training could effectively reduce the risk of subsequent clinical events in HF patients, but did not examine whether greater volumes of exercise conferred a greater reduction in clinical events. In a new sub-analysis of the initial study appearing in JACC, Steven J. Keteyian, PhD, from the department of cardiovascular medicine at Henry Ford Hospital in Detroit, and colleagues found that, in some respects, greater amounts of exercise led to greater decrease in clinical event rates.
HF-ACTION randomly assigned 2,331 patients to usual care alone or usual care plus aerobic exercise training. In the current study, Keteyian et al. evaluated the relationship between exercise volume (EV) and clinical outcomes in a subset of 959 patients randomized to the exercise training arm who were event-free for at least three months. All patients in the study were given educational material recommending 30 minutes of moderate-intensity activity most days of the week. Patients in the exercise training arm began with supervised exercise sessions three days per week and transitioned to a five-day per week at-home exercise program. EV was quantified as metabolic equivalent (MET-h; the product of exercise intensity and number of hours of exercise per week). The primary outcome measure was all-cause mortality or hospitalization; secondary outcomes were the disease-specific endpoint of CV mortality or HF hospitalization and change in exercise capacity as measured by peak oxygen uptake (VO2).
When treated as a continuous variable in linear regression analyses, EV was not significantly predictive of the primary endpoint of all-cause mortality or hospitalization (p = 0.18); however, when EV was evaluated as a logarithmic predictor, it did significantly predict reduction in risk of the primary outcome (p = 0.03). Regarding the CV mortality or HF hospitalization endpoint, EV was significantly predictive, in both linear and logarithmic models—a finding the authors attribute to the fact that EV exerts a greater effect on CV mortality or HF hospitalization specifically as opposed to all-cause mortality and hospitalization.
For both clinical endpoints, Keteyian et al. reported that an exercise volume ≥7 MET-h per week was associated with a smaller decrease in adjusted risk than both the 3 to <5 MET-h per week and 5 to <7 MET-h per week groups. This relationship resulted from the fact that a higher exercise volume was associated with a higher peak VO2, and that peak VO2 was highly associated with clinical outcome (adjusted p < 0.0001).
Ultimately, this substudy analysis extends the findings from the larger HF-ACTION trial: even moderate EV (between 3 and 7 MET-h per week) were associated with reductions in adjusted risk that exceeded 30 percent, the authors concluded, providing support for the use of moderate, regular exercise in the management of patients with chronic systolic HF.
- Keteyian SJ, Leifer ES, Houston-Miller N, et al. J Am Coll Cardiol. 2012;60:1899-1905.
Keywords: Odds Ratio, Inflammation, Colchicine, Exercise, Interleukin-6, Pulmonary Veins, Postpericardiotomy Syndrome, Biomarkers, Heart Failure, Oxygen, Metabolic Equivalent, Catheter Ablation, Hypertension
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