Flecainide is safe and effective

MADRID, SPAIN. Flecainide (Tambocor) is a class 1C antiarrhythmic drug that blocks the inflow of sodium into heart cells thereby slowing conduction through the heart. It increases the atrial effective refractory period (the time span during a heart beat in which AF cannot be initiated). The drug is highly bioavailable in its oral form (90-95% bioavailability) and has a half-life of 12 to 27 hours. Flecainide was first introduced in Europe in 1982, but its acceptance in North America has been very slow with sales taking a dramatic drop (75%) after the publication of the CAST trial which showed increased mortality among patients who had suffered a heart attack prior to initiating treatment with class 1C drugs (flecainide, propafenone). It is now clear that the increased mortality seen in CAST was caused by pro-arrhythmic events in elderly patients with significant pre-existing cardiovascular comorbidity. Thus, flecainide is now recommended in current guidelines as a first-line treatment option for the conversion of atrial fibrillation (AF) to normal sinus rhythm (NSR) and for the maintenance of sinus rhythm in afibbers with no heart disease and normal left ventricular function.

The progression of AF through more frequent and longer episodes to persistent and, in some cases, permanent AF is caused by electrical and structural remodeling of the atrium. Flecainide helps prevent electrical remodeling by slowing conduction across the myocardium and increasing the refractory period. It helps prevent structural remodeling by reducing calcium ion accumulation in the myocytes and the associated oxidative stress. However, like any drug, flecainide does have the potential for adverse effects. It can initiate atrial flutter and, as it does not slow conduction through the AV node, the flutter may result in 1:1 conduction which is clearly dangerous and highly uncomfortable. The risk of this complication is likely associated with pre-existing, perhaps asymptomatic, right atrial flutter and can be eliminated through a right atrial isthmus ablation. Beta-blockers and calcium channel blockers are also effective in preventing 1:1 conduction. The risk of a pro- arrhythmic event also increases with depressed left ventricular ejection fraction, so flecainide is not recommend for AF patients with this condition.

Nevertheless, the overall safety profile of flecainide, when given to appropriately selected patients, is very favourable with a recent study finding overall mortality in flecainide-treated patients to be lower than the expected rate in the general population. The “official” recommendation is that the oral drug, when first prescribed, should be administered in a hospital setting with a gradual increase from 50 mg twice a day to the maximum dose of 150 mg twice a day (if needed). For patients not able to tolerate high doses or having impaired kidney function, a time-release version is available. Some physicians routinely prescribe digoxin or a beta-blocker with flecainide to avoid the possibility of flutter-induced 1:1 conduction.

Intravenous infusion of flecainide is highly effective in chemically converting acute-onset (less than 48 hours duration) AF and restores NSR within an hour in 95% of patients. There is also evidence that flecainide given prior to electrical cardioversion increases the likelihood of first shocks being successful in converting the patient to NSR (65% conversion vs 30% with placebo). Oral administration is also effective if used soon after episode onset. A single loading dose of 200 to 300 mg converts 50-60% of patients within 3 hours and 75-85% within 6 to 8 hours. Although generally safe in healthy afibbers, reversion to NSR may be preceded by a longish pause in heart beat or, in a small minority (0.2%), in 1:1 conduction, particularly if reversion to NSR happens during exercise. Flecainide is also effective in maintaining NSR after conversion with only a 38% relapse rate (over a minimum 6-month follow-up) as compared to relapse rates of 58% for sotalol and 61% for propafenone.

Long-term therapy with oral flecainide has been shown to significantly reduce the frequency of AF episodes with 65% of patients being responsive to therapy in the short-term and 49% responding in the long-term. There is also evidence that flecainide suppresses palpitations, tachycardia, and episode-associated chest pain.

The group of electrophysiologists, with members form France, Germany, Italy, the Netherlands and Spain, compiling this report concludes that administration of flecainide is a safe and effective option in younger AF patients without co-existing structural heart disease.

Aliot, E, et al. Twenty-five years in the making: flecainide is safe and effective for management of atrial fibrillation. Europace, Vol. 13, 2011, pp. 161-73

Editor’s comment: I have always maintained that AF is not just a disease of the elderly, as is the position of mainstream medicine. In LAF Survey 9 (December 2005), I made the comment, “With an average age at onset of 48 years, lone AF is clearly not an old age disease, but rather a condition that strikes in what, for most people, is their most productive years. Only 7% of the 619 afibbers in our sample group were diagnosed as late as 65 years of age or older, while 10% were diagnosed before reaching the age of 30 years. A massive 60% were diagnosed at or before the age of 50 years.” It is therefore very gratifying to see that mainstream thinking may be slowly changing as indicated in the following remark from the above article, “Atrial fibrillation is widely accepted as a condition of the elderly; however, around half of patients presenting with paroxysmal atrial fibrillation are less than 60 years old.”