Letter by Reiffel Regarding Article, “Acute Pharmacological Conversion of Atrial Fibrillation to Sinus Rhythm”
To the Editor:
I read with great interest the Special Report by Drs William Hiatt, Michael Lincoff, and Robert Harrington1 on acute pharmacological conversion of atrial fibrillation (AF) to sinus rhythm. Their report provides the reader some fascinating insight into the deliberations of the Cardiovascular and Renal Drugs Advisory Committee, as well as a glimpse into the authors’ personal opinions as to the value (or lack thereof) of pharmacological cardioversion. In my opinion, although their thoughtful deliberations raised some significant and valid issues for consideration, several important points related to this topic were presented in a biased manner or not even considered. (1) The success of cardioversion is time dependent, especially for drug conversion, and “watchful waiting,” as was discussed several times in the report, would have been detrimental to success in the trials (especially because many of the patients were not treated on the first day of their AF) and misleading to practitioners, who must ultimately consider using such therapy if/when available. A no-treatment run-in phase, as suggested by the authors, clearly would also have been adverse to successful results. Moreover, in clinical practice in which the drugs being considered would be used, waiting for spontaneous conversion for >24 hours is generally not practiced unless the patient is both anticoagulated and tolerating their AF well. (2) The risk of thromboembolism is also time dependent after the onset of AF, and watchful waiting may increase its risk or increase the need for initiation of anticoagulation and its accompanying risks, a major concern for patients and practitioners alike. (3) The concern about QT prolongation and torsade de pointes proarrhythmia is certainly valid for current class III agents, but it is not a concern with class IC drugs, which was misstated in the report. (4) The data set of the drugs considered was thought to be small; yet, it is substantially larger than the pivotal trials that resulted in Food and Drug Administration approval for flecainide, propafenone, and sotalol for treatment of AF. (5) Perhaps most importantly, the issue of watchful waiting should really be a nonissue, because that is inherently what was done in the placebo arms of the trials reviewed in the report. (6) In addition, although the authors note that direct current (DC) cardioversion could be performed and that when done after drug failure, it did allow the total number of patients attaining sinus rhythm to be essentially similar in the drug and placebo groups, the authors did not address several substantial items. These include the risks and costs associated with DC shock in this setting; the risks and costs associated with the anesthesia required for DC cardioversion; the fact that the total costs exceed those of pharmacological cardioversion; the skin discomfort that often follows DC cardioversion; and the need to reevaluate implanted devices after DC shock if such are present. DC cardioversion is not a panacea; moreover, it can happen that emergent (but not instantaneously emergent) cardioversion is sometimes needed but anesthesia for DC shock is contraindicated. In such cases, pharmacological conversion with an intravenous agent is the clinical procedure of choice, and a safer choice than ibutilide remains a clinical necessity for practitioners. Thus, I believe the overall risk-to-benefit profile as noted by the committee according to the report may have been calculated in a biased manner against the drugs that were considered, at least as far as vernakalant goes.
Dr Reiffel has served on the advisory board and/or speakers’ bureau for Astellas Pharma, Cardiome, GlaxoSmithKline, Pharmacia, Reliant Pharmaceuticals, CV Therapeutics, and Sanofi-Aventis.
Hiatt WR, Lincoff AM, Harrington RA. Acute pharmacological conversion of atrial fibrillation to sinus rhythm: is short-term symptomatic therapy worth it? A report from the December 2007 Meeting of the Cardiovascular and Renal Drugs Advisory Committee of the Food and Drug Administration. Circulation. 2008; 117: 2956–2957.