Changing pattern of drug therapy for AF

VANCOUVER, CANADA. Pharmaceutical drug therapy for atrial fibrillation is designed to either re-establish and maintain normal sinus rhythm (NSR) through the use of antiarrhythmic drugs (rhythm control), or to maintain a safe and comfortable ventricular rate (pulse rate) through the use of beta-blockers, calcium channel blockers or digoxin (rate control). Several trials have demonstrated that there is no significant difference in outcome (survival, stroke prevention, and quality of life) for the two protocols.

A group of Canadian researchers has investigated the changing patterns in pharmacological treatment of AF during the period 1991 to 2007. Their study included 1400 patients with new onset afib enrolled in the Canadian Registry of Atrial Fibrillation (CARAF). Among the highlights of their findings are:

  • The proportion of patients receiving antiarrhythmic drugs (AADs) increased from 26.9% in 1991 to 42.4% in 1994, but then declined steadily to about 22% in 2007. Throughout the 1990s sotalol was the most prescribed AAD, peaking in 1993 at 27%. Subsequently its use declined steadily to 6% in 2007. Amiodarone prescriptions increased from 1.6% in 1991 to 17.9% in 2007. Propafenone was also quite popular in the 1990s peaking at 13.3% in 1995 and declining to about 2% in 2007. Flecainide use was low throughout the study period peaking at 2.0% in 2001. NOTE: The low use of flecainide and propafenone may indicate that most patients enrolled in CARAF had underlying heart disease and thus were not suitable candidates for therapy using these two Class 1C drugs. Quinidine was used by 9.5% of patients in 1995 but by 2005 it was no longer prescribed.

  • The proportion of patients receiving rate control drugs exclusively decreased from a peak of 54.2% in 1991 to 34.1% in 1995. By 2000 the use of rate control started increasing again reaching 52.5% by 2007. In the early 1990s digoxin was the preferred rate control medication with 62.9% of patients using it. By 2007 this proportion had declined to 16.3%. The use of beta-blockers increased from 20.2% in 1991 to about 40% in 2007. Use of calcium channel blockers remained fairly steady over the 16-year period increasing from 14.3% in 1991 to 16.3% in 2007.

  • About 50% of patients using rhythm control were also prescribed rate control drugs. Combinations of rate control drugs were frequently used with beta-blocker + digoxin being popular in the early years and beta-blockers + calcium channel blockers gaining popularity in later years.

  • Patients receiving neither rhythm control nor rate control were significantly younger and were less likely to have hypertension or underlying heart disease. However, most of patients in this group (73%) had symptomatic afib.

  • The CARAF Study confirmed other findings that paroxysmal afib tends to progress to the permanent variety. At first year of follow-up, 10-15% were in permanent afib as compared to 37% at the 10-year follow-up.

The authors make the following interesting comment about the reason for the decline in the use of AADs, “It may be that the observed longitudinal decline in AAD use was merely a reflection of the acceptance of permanent AF by patients and their treating physicians, with a resultant shift toward a goal of ventricular rate control.”

Andrade, JG, et al. Antiarrhythmic use from 1991 to 2007: Insights from the Canadian Registry of Atrial Fibrillation (CARAF I and II). Heart Rhythm, Vol. 7, September 2010, pp. 1171-77

Editor’s comment: It is indeed gratifying to see the significant decrease in prescriptions for digoxin and sotalol. For lone afibbers at least these two drugs are ineffective and in the case of digoxin downright dangerous. The growing enthusiasm for rate control was largely fuelled by the results of the AFFIRM trial which found no significant difference in 5-year mortality between patients assigned to rhythm or rate control. Only 12% of the participants had lone afib and to quote the authors, “the results probably cannot be generalized to younger patients without risk factors for stroke (i.e. patients with primary, or “lone” atrial fibrillation), particularly those with paroxysmal atrial fibrillation.”

Quite apart from the fact that the study is not particularly applicable to lone afibbers, I believe it had several serious flaws:

  • The most “popular” drug used in the trial was digoxin. Over 70% of the people in the rate control group had used this drug at one time or another. Digoxin had been used by 54% of the participants in the rhythm control group as well. So as far as digoxin use is concerned, there was little difference between the two groups.
  • Beta-blockers were used liberally in both groups as well – 68% in the rate control group and 50% in the rhythm control group.
  • The main antiarrhythmic used was amiodarone (Cordarone). This drug was used by 63% of the patients in the rhythm control group and by 10% in the rate control group.
  • The second most popular “antiarrhythmic” used in the rhythm control group was sotalol (Betapace) – this drug was used by 41% of patients despite the fact that it is well known that it does little, if anything, to maintain sinus rhythm, although it may help control the heart rate during an afib episode.
  • Propafenone, flecainide and disopyramide had been used by only 4-15% of patients in the rhythm control group. It is impossible to say whether any of these drugs were beneficial or detrimental because of the way the data is reported.

The significant overlap in drug use between the two groups (especially in regards to digoxin) and the low usage of Class I antiarrhythmics detract somewhat from the value of the study.