Verapamil better than betablockers for preventing AF progression: RACE-4 trial

Rate control for Atrial fibrillation (AF) is largely achieved by betablockers and calcium channel blockers. Mostly it is the clinician's choice that decides which drug class is to be used as both these classes of drugs have shown good results over the years. But does it make a difference if we prefer a particular class over other? Can either of these delay the progression of paroxysmal episodes of AF to more permanent forms.

Progression from paroxysmal AF to persistent or permanent AF is associated with increased disease burden, and hospitalization rates and this progression is dependent on structural and electrical remodelling of the atria. In a prespecified post hoc analysis of RACE-4 trial, Koldenhof et have shown that in patients with newly diagnosed paroxysmal AF, verapamil was associated with less AF progression, as compared to beta blockers. This study has been recently published in EP Europace journal.

Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia, with a lifetime risk of 23%. Several studies have shown that non-dihydropyridine calcium channel antagonists (CCA), such as verapamil, reduce tachycardia-induced electrical remodelling in AF.

Furthermore, in contrast to beta blockers, verapamil increases sympathetic tone that can theoretically suppress ectopic activity in atria. In patients with vagal paroxysmal AF, verapamil has shown to reduce progression to persistent AF compared to digoxin and beta blockers.

Koldenhof et al identified patients with paroxysmal AF using verapamil, beta blockers, or no rate control medication at their first outpatient visit and compared their effect on AF progression. AF progression was defined as the need for atrial ablation, electrical cardioversion (ECV), or chemical cardioversion (CCV), all an expression of progressive symptoms as well as AF persistence.

In this pre-specified post hoc analysis of the RACE 4 randomized trial, patients using Vaughan-Williams Class I or III antiarrhythmic drugs were excluded. The primary outcome was a composite of first electrical cardioversion (ECV), chemical cardioversion (CCV), or atrial ablation.

Out of 666 patients with paroxysmal AF, 47 used verapamil, 383 used beta blockers, and 236 did not use rate control drugs. The verapamil group was significantly younger than the beta blocker group and contained more men than the no rate control group.

Over a mean follow-up of 37 months, the primary outcome occurred in 17% in the verapamil group, 33% in the beta blocker group, and 33% in the no rate control group (P = 0.038).

After adjusting for baseline characteristics, patients using verapamil have a significantly lower chance of receiving ECV, CCV, or atrial ablation compared to patients using beta blockers and no rate control.

"These results could be due to the electrophysiological effects of verapamil", point authors in the discussion. Rapid atrial rates lead to calcium loading in the sarcoplasmic reticulum and increased calcium leakage from the sarcoplasmic reticulum. This calcium leak from the sarcoplasmic reticulum promotes cellular arrhythmogenesis in paroxysmal AF patients by inducing delayed afterdepolarization and triggered activity.The decrease in AF progression in the verapamil group might be explained by verapamil preventing or delaying electrical remodelling.

Authors add, "verapamil specifically lowers the heart rate during AF, but not during sinus rhythm. In contrast, the dose of beta blockers and their rate controlling effect during paroxysms of AF is limited by the heart rate during sinus rhythm. Therefore, heart rate during AF episodes in the beta blocker patients may have been more rapid, with the risk of ventricular dysfunction and subsequent atrial structural remodelling and AF progression."

These results justify further study of the effects of verapamil on AF progression in patients with paroxysmal AF with a randomized controlled trial.

Source: EP Europace: doi:10.1093/europace/euab191