Heart & Vascular Institute Physician eNewsletter - Spring 2011
AF is the most common arrhythmia problem, and medications have traditionally been useful for managing the condition. But the more Cleveland Clinic cardiologists and electrophysiologists follow patients taking medications to control their rhythm or prevent stroke, the more they realize that the long-term effects of drug therapy can result in adverse side effects or risks.
In the past decade, the movement toward ablation for AF has proved effective, and as shown in several large, multi-center trials, ablation actually serves as a better solution for some patients.
"Four years ago, I would have said that patients should try medications first before ablation, and I almost always do use medications first," says Bruce D. Lindsay, MD, FACC, FHRS, section head, Electrophysiology & Pacing for Cleveland Clinic Heart & Vascular Institute. "But if a patient has reviewed all the information we provide and understands what is involved in ablation and wants to make an informed decision, it’s reasonable to proceed to the ablation procedure. As technologies and techniques improve, we can continue to improve the success rate for a single ablation procedure."
Drug Therapy for AF
One of the big problems physicians confront when treating AF is depicted here (figure 1). Warfarin as a drug can be difficult to regulate and patient response is sometimes challenging to predict. Also, considering the narrow therapeutic window in the chart, if the International Normalized Ratio (INR) measuring how long it takes blood to clot is not in that 65-percent range most of the time, the patient does not benefit much from taking Warfarin. If the INR is too low, there is a steep increase in stroke risk, which drives up the risk of intercranial hemorrhage.
Figure 1: Relationship Between Clinical Events and INR—Intensity in Patients with Atrial Fibrillation
Meanwhile, a study of patients who were not eligible for Warfarin but instead took a combination of aspirin and Clopidogrel, showed a distinct advantage with fewer strokes, but more bleeding. "There is some advantage in reducing stroke with the combination of aspirin and Clopidogrel, but when you compare that to Coumadin, it is not as effective," Dr. Lindsay points out (figure 2).
Figure 2: Active A: Primary Outcomes—Stroke, MI, Non-CNS, Systemic Embolism and Vascular Death
The question: Where do we go from here, especially because of questions surrounding Coumadin and its side effects?
One answer could be dabigatran, a newer anticoagulant drug that showed a lower risk of intercranial hemorrhage in the RE-LY non-inferiority trial. In another study comparing the antiarrhythmic medication dronedaron with a placebo, the rate of first hospitalization for death was significantly reduced at a mean follow-up of 21 months with dronedaron. However, the dronedarone group has higher rates of bradycardia, QT-interval prolongation, nausea, diarrhea, rash and increased serum creatinine levels (figure 3). In one trial involving patients with severe heart failure, dronedarone was found to increase overall mortality, raising serious concern about the safety of this drug for patients with advanced heart failure.
Overall, the efficacy of dronedaron for AF is about 40 to 45 percent.
Dr. Lindsay says the underlying message is that medications are limiting and ablation can be a more effective, lasting treatment for patients with AF. Whether ablation eliminates the risk of stroke is still being studied.
Opting for Ablation
Today, it’s the electrophysiologists job to not just perform ablation procedures, but to educate patients who are dealing with AF about available options so they can make an informed decision. Each patient’s situation is different, so there is no one ideal treatment for AF, Dr. Lindsay says.
With focal ablation, which involves blockage of electrical signals to the pulmonary veins, ablation techniques have evolved to include the pulmonary vein antral regions. The single procedure efficacy for paroxysmal AF is 60 to 80 percent (redo rates are about 20 to 30 percent); and efficacy for persistent AF is 40 to 60 percent. In reviewing Cleveland Clinic data from 2009, there were no deaths, strokes, or esophageal injuries in the patients who received focal ablation for paroxysmal or persistent AF. At experienced centers the mortality rate is 0.1 to 0.2 percent. Risk of pulmonary vein stenosis is 1 percent or less.
In randomized trials, the efficacy of ablation vs. medications is 58 to 88 percent effective for ablation vs. 7 to 45 percent for medications (table 1).
"The direct comparisons we have thus far suggest that ablation therapy is superior to drug therapy for treatment of AF, but treating with one or two antiarrhythmic drugs is advisable before proceeding to ablation," Dr. Lindsay says. CABANA is a national multicenter study designed to compare long term outcomes of ablation compared with medical therapy. This study will evaluate the effectiveness of these approaches and compare the risk of stroke, hospitalization, and death.
Hybrid therapy is important for many patients. "Sometimes after an ablation, patients with complex heart disease may require drug therapy after ablation to manage the condition," Dr. Lindsay says.