I was dismayed by the specifics of the comparison by Ulimoen et al of 4 drug regimens for the rate control of atrial fibrillation. This RATe Control in Atrial Fibrillation (RATAF) trial was a good idea, but it compared unequivalent medication dosages.

Extended release diltaizem at 360 mg/day—a standard maximum dose—was better than the other regimens studied because it was a full medication dose and dosed correctly. Extended release verapamil was given at 240 mg/day, although the usual maximum dose is 360 mg/day. Extended release metoprolol (succinate) was given at 100 mg/day, although the usual target dose for all indications is 200 mg/day.

Most disturbingly, short-acting carvedilol was given at 25 mg once daily. Not only is this ½ the target dose, but the drug is always recommended for twice daily dosing. A carvedilol phosphate formulation is available at additional cost for daily dosing. This use of once-daily carvedilol raises nasty concerns of trial safety. For those of us who frequently prescribe carvedilol and whose patients might occasionally forget a dose, it is reassuring to find that this dosing was not associated with adverse events in their trial. Still, daily dosing of short-acting carvedilol is simply wrong.

Their trial has parallels that of the POISE study, in which a long-acting drug was given in an unsafe manner and was then deemed inferior. Perhaps some of these trials were agenda driven. Whatever the motive, any drug in any formulary is either useless or deadly if dosed improperly.