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Atrial Fibrillation: Current Management and Best Practices

Atrial Fibrillation: Current Management and Best Practices

To rule out the presence of a thrombus in the left atrium prior to CA, all patients underwent transesophageal echocardiography prior to the procedure. Patients in the dabigatran group were given the morning dose of the regimen prior to the ablation and the evening dose timed to occur at least 3 hours after sheath removal and after the achievement of hemostasis. As described in the VENTURE-AF study, all patients were given UFH during the procedure to maintain the goal ACT of >300 seconds. While radiofrequency was the primary technique used in this study, other modalities were allowed, including cryoablation and laser ablation. Ablation was performed as determined by the attending electrophysiologist and according to recommendations and guidelines based on the 2012 expert consensus statement. Several safety and efficacy endpoints were evaluated in this study; however, the primary endpoint was incidence of adjudicated ISTH major bleeding events. Events occurring from the start of the ablation procedure up to 8 weeks post ablation were included in the analysis. Secondary endpoints for this study included incidence of a composite of stroke; systemic embolism or transient ischemic attack (TIA); minor bleeding events; and bleeding events combined with thromboembolic events (stroke, systemic embolism or TIA).  In order to have enough power to determine statistical significance for noninferiority, each treatment group would have needed more than 2000 patients. Since the researchers thought this was unfeasible, an exploratory approach was used similar to that of the VENTURE-AF trial, and it was determined that clinically meaningful data could be provided if a goal of 290 patients per treatment group was met. A total of 317 patients were randomized to the dabigatran group and 318 to the warfarin group. Both demographic and clinical characteristics were similar among treatment groups. Most patients enrolled in the study were diagnosed with paroxysmal AF. The mean age of patients included in the study was 59 years and patients were predominately men (73%).36 Adherence rates for patients receiving dabigatran was determined by calculating the number of pills taken. Patients who had not met 80% to 120% of the anticipated dose were considered nonadherent. The mean adherence rate for patients taking dabigatran was 97.6%. To determine adherence in the warfarin group, a therapeutic INR goal of 2.0-3.0 was used. Patients in the INR-adjusted warfarin group were within goal INR range 66% of the time. A total of 86% of dabigatran patients and 84% of warfarin patients received trial medication for at least 8 weeks post ablation, and more than 98% of trial participants received medication for at least 6 weeks. Incidence of major bleeding events, the primary endpoint of the study, was observed in 1.6% of patients in the dabigatran group and 6.9% of patients in the warfarin group (95% CI, –8.4 to –2.2; P <.001). Cox proportional-hazards analysis demonstrated a hazard ratio of 0.22 (95% CI, 0.08-0.59) for dabigatran compared with warfarin.36

Use of anticoagulation of any mechanism is associated with a risk of bleeding. Events of pericardial tamponade, groin hematoma, intracranial bleeding, gastrointestinal bleeding, pseudoaneurysm, and hematoma were observed less frequently in the dabigatran group than in the warfarin group. There were 4 major bleeding events in the dabigatran group within 7 days post ablation, compared with 17 events in the warfarin group. Comparing patients in the warfarin group with and without major bleeding events, the mean INR was similar (2.4 vs 2.3).36

Secondary outcomes in this study included incidence of stroke, systemic embolism, or TIA, and the rate of serious AEs. A serious AE in patients who had taken at least 1 dose of the study drug occurred in 22.2% of the warfarin group and 18.6% of the dabigatran group. Severe events were observed in 3.3% of dabigatran patients versus 6.2% of warfarin patients.36

In addition to bleeding risks, stroke is a potential complication in patients undergoing CA. No reports of stroke or TIA were reported in the dabigatran group and only 1 TIA occurred in the warfarin group. The composite of major bleeding and thromboembolic events was 1.6% in the dabigatran group versus 7.2% in the warfarin group.36

Analysis of the results indicates significantly lower rates of major bleeding events in the dabigatran group. Of particular note were fewer incidents of groin hematoma and life-threatening bleeds such as pericardial tamponade. Researchers postulated that the observed differences in bleeding events might be related to 2 specific factors. First, they referenced the shorter half-life of dabigatran versus treatment with a VKA, which has a much longer half-life. Secondly, the authors pointed out that dabigatran’s mechanism of action through direct thrombin inhibition preserves factor VII levels, whereas VKA exhibits a broad-spectrum anticoagulation by impacting several coagulation factors, including factor VII. As in the VENTURE-AF trial, the RE-CIRCUIT trial lacks statistical power due to the small sample size as well as the open-label design.36

The authors noted a recent meta-analysis, involving 7996 patients from 19 observational studies, that supports the use of an uninterrupted NOAC as a viable treatment strategy to prevent thromboembolic events in patients undergoing CA. The study indicated that NOACs may be associated with a lower rate of bleeding complications.36 Results from the RE-LY trial, which demonstrated an advantage of dabigatran over VKA, add to the growing evidence of the safety and efficacy of utilizing NOACs in patients with AF.36

Managed Care Implications
Evidence suggests that AF cost-reduction strategies can be effective by shifting cost from inpatient to outpatient care. Utilization of treatment algorithms in the emergency department have been shown to be effective in avoiding hospital admission and allowing for follow-up in AF clinics in the outpatient setting to reduce costs. When developing algorithms, it is important to note that evidence suggests rate control is a more cost-effective approach than rhythm control. Additionally, improving utilization, management, and adherence to anticoagulation therapy has been shown in numerous studies to improve outcomes and should be part of focused efforts in this heavily “at risk” population.7

Over the last 15 years, CA has evolved and emerged as the primary treatment option available for rhythm control.4 With older literature references demonstrating success rates that varied widely, recent studies suggest that success rates of >80% can be achieved in patients with paroxysmal AF.7 However, it has been difficult to demonstrate AF as a cost-effective strategy in all cases due to the inherent difficulties in study comparisons and the subsequent ability to generalize results.4,7 Utilization of different technologies (radiofrequency ablation vs cryoablation), different measurements of success, and a general lack of understanding of the long-term effects of CA on cost and outcomes in patients with AF, all contribute to the need for further study.4

Chang et al performed a literature review on the cost-effectiveness of CA; all studies they reviewed used a modeling-based approach to extrapolate the impact of CA. They noted that existing randomized controlled trials for CA in AF have failed to report long-term cost and quality-of-life (QOL) results.4 In the cost-effectiveness analysis studies, Chang et al found that several input assumptions made by the authors of the individual studies could substantially change the results and must be confirmed (or challenged) with further research. To achieve greater modeling accuracy, Chang et al suggested that more needs to be known about CA, including long-term outcomes and costs. They outlined a framework for further study that includes measuring effect on QOL, calculating ability to maintain normal sinus rhythm, and tabulating readmissions associated with recurrent AF, as well as quantifying the interrelationship among CA and HF, stroke, and mortality. Variability in these factors can push the incremental cost-effectiveness ratio calculation beyond the “willingness-to-pay” threshold of $100,000 per quality-adjusted life-year.4

Given the current literature available, evidence suggests that CA may achieve the most benefit in younger patients with symptomatic disease, especially those who fail antiarrhythmic drug treatment. Further study would be needed to justify the use of CA in all cases, across the board, given the facts that complications related to the procedure can certainly outweigh its benefits, and that lower-cost alternatives, such as pharmacologic rate control, are better understood. Advances in technology may also improve outcomes, as well as lower the costs and decrease the risks associated with CA.4

While there are other methods of CA not mentioned here, it is certain that reducing thromboembolic complications using safe and effective uninterrupted anticoagulation is of prime importance. Until recently, standard of care has been to stop VKA therapy and bridge patients with LMWH prior to and after CA. However, as previously mentioned, studies have shown that this may not be the safest, nor the most effective, strategy.

Evidence appears to favor the utilization of uninterrupted anticoagulation utilizing either a VKA or an NOAC, such as dabigatran or rivaroxaban, prior to and post CA.33

By reducing thromboembolic complications and minimizing bleeding events, overall costs of care would be reduced. Given the rising healthcare costs attributed to AF, any incremental reduction in costs benefits not only the patient, but the entire healthcare system.

Given the small sample sizes and lack of statistically powered results, managed care providers should be cautious not to overgeneralize the results of these studies. However, given that bridging patients on NOACs or with a VKA is a practice existing today, and new data to support this practice are available, there does appear to be an opportunity to reduce the direct costs associated with the more traditional strategy of bridging VKA patients with LMWH. Certainly, reviewing internal quality metrics related to CA, and reviewing outcomes and complications, should help to drive medical policy. It should be a reasonable goal to develop treatment algorithms, with the input of cardiovascular specialists who perform CA, without relying on older, less effective practices that lead to more complications, yet ensuring that patients enjoy uninterrupted anticoagulation prior to and post CA. Collecting data and reviewing outcomes using uninterrupted VKA and newer NOACs should help to further drive practice changes. And although a reversal agent was available during the time of the RE-CIRCUIT trial, major bleeding events were managed without the need to use the drug. Under study conditions, it would be expected that the goal would be to minimize the use of reversal agents; however, in a real-world practice setting, the inappropriate use of expensive reversal agents has the potential to drive up costs and should be monitored closely. From a managed care perspective, identifying centers of excellence that perform these procedures with the fewest complications and the most effective outcomes, and that are reproducible at the lowest cost, should help to drive medical policy and population management. 

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