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We would like to thank Dr. Coceani for his interest in our recent publication (1) and the opportunity to discuss his comments. He lists a series of reports that implicate worse cardiovascular (CV) outcomes with specific type 3 agents in particular subsets of patients with atrial fibrillation (AF). The observations in these selected reports have to be put in context of a much larger body of data that suggests that these agents are effective in restoring sinus rhythm and do not uniformly increase risk (2). Systematic review of all AF rhythm control therapy trials has also suggested excess risk with type 1 drugs. Mixed treatment analyses have also suggested some differences in efficacy and tolerability of type 3 drugs (3). We think it is important to consider the totality of the evidence and carefully select antiarrhythmic drugs for individual patients. We believe that our report can shed light on these varying results as well as define some new goals and influence designs and outcome measures of future clinical trials.
Our analysis highlights:
1. The choice of initial antiarrhythmic drug is an independent variable determining CV outcome.
2. The importance of baseline patient status and comorbidities is evident in our results. For example, coronary disease and a history of a heart failure event uniformly adversely affected CV outcome for all antiarrhythmic drugs analyzed. Specific concerns existed with individual drugs such as selection of sotalol as initial therapy in women or thyroid disease (treated or untreated) with amiodarone.
3. Worsening status of specific comorbidities, such as heart failure and ischemic heart disease, impacted outcomes.
4. Time-dependent analysis noted fewer CV events occurred in sinus rhythm.
The available clinical trial data and Dr. Coceani's highlighted subgroups probably arrived at their outcomes based on the specific combinations of these variables and the choice and effectiveness of the individual antiarrhythmic agent.
We believe that the implications of these observations could be:
1. More critical screening of AF patients for baseline clinical variables to permit more careful selection of an appropriate initial antiarrhythmic drug
2. Aggressive treatment of comorbidities to prevent disease progression
3. Quantitative assessment of sinus rhythm maintenance for effective rhythm control
We would suggest that Dr. Coceani's suggestion to “shelve type 3 antiarrhythmic drugs in current use” be restated to “carefully select the most appropriate initial drug and consider newer therapeutic options for rate and rhythm control in patients that are not suitable for currently available drugs” (4). Most importantly, we agree with Dr. Coceani regarding the need to seek newer and more effective therapies to restore and maintain sinus rhythm and upstream therapies to prevent progression of the disease and, by implication, the AF substrate.
- American College of Cardiology Foundation
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- Freemantle N.,
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- Saksena S.,
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