Elsevier

Heart Rhythm

Volume 7, Issue 9, September 2010, Pages 1171-1177
Heart Rhythm

Focus issue: Atrial fibrillation
Clinical
Antiarrhythmic use from 1991 to 2007: Insights from the Canadian Registry of Atrial Fibrillation (CARAF I and II)

https://doi.org/10.1016/j.hrthm.2010.04.026Get rights and content

Background

The pharmacologic management of atrial fibrillation (AF), the most common sustained cardiac arrhythmia, has been traditionally dichotomized into control of ventricular rate or re-establishment and maintenance of sinus rhythm.

Objective

The purpose of this study was to evaluate the use of rate-controlling drugs and antiarrhythmic drugs (AAD) in the Canadian Registry of Atrial Fibrillation (CARAF) over a 16-year period from 1991 through 2007.

Methods

1,400 patients with new-onset paroxysmal AF who were enrolled in CARAF were included in this analysis. We assessed trends in ventricular rate-controlling medication use (digoxin, beta-blockers, and calcium channel blockers) and AAD (class IA, IC, and III antiarrhythmic agents) at baseline and follow-up visits as well as by calendar year.

Results

AAD use increased initially from 1991 to 1994 (peak use 42.5%) before steadily declining. Sotalol use decreased (27% to 6%), whereas amiodarone use increased (1.6% to 17.9%). Rate-controlling medication use decreased from 1991 to 1995 (54.1% to 34.1%) due to declining digoxin use (62.9% to 16.3%). After 1999, there was a continued increase in rate-controlling medication use (peak use 52.5% in 2007) due to increased beta-blocker use (17% to 45.7%). Calcium channel blockers use changed little over the duration of the study.

Conclusion

The management of AF has undergone significant shifts since 1990, reflecting the influence of drug development, prevailing belief systems, the impact of large clinical trials, and evidence-based recommendations. Monitoring of pharmacotherapy trends will provide insight into the real-world application of evidence-based guidelines as well as allow the opportunity to identify deficiencies and improve patient care.

Introduction

Atrial fibrillation (AF) is the most common sustained arrhythmia seen in clinical practice. AF affects nearly 2.5 million Americans and 4.5 million Europeans, and as a result, accounts for the majority of arrhythmia-related physician visits and hospital admissions.1, 2, 3 Although the majority of these cases are not immediately life threatening, AF is associated with significant complications, such as stroke, as well as reductions in quality of life, functional status, and cardiac performance. In addition, patients with AF are at higher risk of overall mortality when compared with non-AF patients.4

The pharmacologic management of AF has been traditionally dichotomized into 2 competing strategies: control of ventricular rate or re-establishment and maintenance of sinus rhythm. Traditionally, the maintenance of sinus rhythm by means of cardioversion followed by the chronic use of antiarrhythmic drugs (AAD) was chosen as the initial therapy for AF. In contrast to the prevailing clinical practice, landmark trials published over the past 10 years have not demonstrated a significant benefit with a strategy of routine rhythm control in respect to survival, stroke prevention, or quality of life. These studies have suggested that a strategy focused on minimizing symptoms and complications with ventricular rate control is equally efficacious, particularly in an elderly, minimally symptomatic patient population.5, 6, 7, 8, 9, 10

The purpose of this study was to evaluate the use of rate-controlling medications and AADs in the Canadian Registry of Atrial Fibrillation (CARAF) over a 16-year period (1991 to 2007). Because CARAF I and CARAF II are nondirected cohorts, they provide the opportunity to evaluate the long-term trends in drug therapy for patients with AF beginning in the 10-year period prior to the publication of the American College of Cardiology/American Heart Association/European Society of Cardiology clinical practice guidelines for the management of AF in 2001 through the publication of the landmark AF trials in the late 1990s to early 2000s.5, 6, 7, 8, 9, 10 As such, it provides unique insight into the use of antiarrhythmic and rate-controlling medications by primary and secondary care physicians over time.

Section snippets

Methods

Detailed methods of the CARAF cohorts have been reported elsewhere.11, 12 Briefly, CARAF I and II are prospective cohort studies that document the natural history and management of patients with new-onset AF or flutter. CARAF I enrolled 1,095 patients in 6 Canadian cities between 1991 and 1996. CARAF II added Toronto to the original 6 cities and enrolled 503 patients between 2001 and 2003. In both cohorts, patients were enrolled from emergency rooms, cardiology laboratories, hospitals, and

Rate versus rhythm control from 1991 to 2007

The proportion of patients in the CARAF studies receiving AADs to maintain sinus rhythm (rhythm control strategy) increased from 26.9% in 1991 to 42.4% in 1994 (Figure 1). There was a steady decline in the frequency of AAD use from a peak in 1994 through the end of follow-up in 2007 (with the exception of a slight increase in use in 2003). In both CARAF I and CARAF II, as well as in the combined cohort, the use of AAD was highest in the first year after AF diagnosis (45.6% for the combined

Discussion

AF and flutter are increasingly common medical problems for which the pharmacologic management has changed significantly over the past 20 years. From these 2 large nondirected prospective cohort studies, we were able to gain insight into the evolving long-term trends in the pharmacologic management of AF beginning in the 10-year period prior to the publication of landmark AF trials in the late 1990s and early 2000s.

Over the course of our study period, the management strategy for AF and flutter

Conclusion

The combined CARAF cohorts provide an 18-year duration of follow-up for newly diagnosed AF patients and offer a unique insight into the use of medications for the maintenance of sinus rhythm as well as the use of medications for the control of ventricular rate. Over this time, the management of AF and flutter has undergone significant shifts reflecting the influence of drug development, prevailing belief systems, and the impact of large clinical trials. As such, continued monitoring of the

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    The Canadian Registry of Atrial Fibrillation has been supported by an unrestricted grant from Sanofi-Aventis Canada (2006–2009), St. Jude Medical (2007), Proctor and Gamble Pharmaceuticals Inc. (1998–2003), Knoll Pharmaceuticals (1991–1997), and Dupont Pharma (1996).

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