The Evidence Regarding the Drugs Used for Ventricular Rate Control
OBJECTIVE: Our goal was to determine what drugs are most effacacious for controlling the ventricular rate in patients with atrial fibrillation.
SEARCH STRATEGY: We conducted a systematic review of the literature published before May 1998, beginning with searches of The Cochrane Collaboration’s CENTRAL database and MEDLINE.
SELECTION CRITERIA: We included English-language articles describing randomized controlled trials of drugs used for heart rate control in adults with atrial fibrillation.
DATA COLLECTION/ANALYSIS: Abstracts of trials were reviewed independently by 2 members of the study team. We reviewed English-language abstracts of non-English-language publications to assess qualitative consistency with our results.
MAIN RESULTS: Forty-five articles evaluating 17 drugs met our criteria for review. In the 5 trials of verapamil and 5 of diltiazem, heart rate was reduced significantly (P<.05), both at rest and with exercise, compared to placebo, with equivalent or improved exercise tolerance in 6 of 7 comparisons. In 7 of 12 comparisons of a beta-blocker with placebo, the beta-blocker was efficacious for control of resting heart rate, with evidence that the effect is drug-specific, as nadolol and atenolol proved to be the most efficacious. All 9 comparisons demonstrated good heart rate control with beta-blockers during exercise, although exercise tolerance was compromised in 3 of 9 comparisons. In 7 of 8 trials, digoxin administered alone slowed the resting heart rate more than placebo, but it did not significantly slow the rate during exercise in 4 studies. The trials evaluating other drugs yielded insufficient evidence to support their use, but those drugs may yet be promising.
CONCLUSIONS: The calcium-channel blockers verapamil or diltiazem, or select {b}-blockers are efficacious for heart rate control at rest and during exercise for patients with atrial fibrillation without a clinically important decrease in exercise tolerance. Digoxin is useful when rate control during exercise is less of a concern.
Despite pharmacologic and electrical interventions, sinus rhythm cannot be restored and maintained in many patients with atrial fibrillation. For these patients, control of the ventricular rate is a primary goal of therapy, since a rapid rate may lead to worsening congestive heart failure, myocardial ischemia, or distressing breathlessness and palpitations.
A number of review articles have described strategies for rate control, principally involving the use of digoxin, calcium-channel blockers, and b-blockers.1-6 A recent analysis of the trends in the use of drugs for ventricular rate control found that the use of digoxin and b-blockers decreased between 1980 and 1981 and 1994 and 1996, and the use of the nondihydropyridine calcium-channel blockers diltiazem and verapamil increased.7 These investigators, however, indicated that “current practices are dictated more by clinical tradition than by clinical science.”7 There has not been a systematic review of the trials evaluating the efficacy of both the familiar and the newer medications for ventricular rate control in atrial fibrillation. It is increasingly clear the drugs that are used most often for heart rate control at rest may not be the most efficacious during exercise, and exercise tolerance is compromised by some drugs.6
The purpose of our review was to characterize the strength of the evidence regarding the efficacy of drugs used for ventricular rate control in atrial fibrillation.
Methods
Study Design
We performed a systematic literature review and synthesis of randomized controlled trials on ventricular rate control in atrial fibrillation. To be eligible for inclusion in our review, trials needed to meet the following criteria: address management of nonpostoperative atrial fibrillation or atrial flutter; include human data; include adult subjects; and present original data. Studies that included patients with postoperative atrial fibrillation were not excluded as long as those patients were only a minority of the included patients.
Literature Identification and Search Strategies
The primary source of literature for our review was the CENTRAL database of The Cochrane Collaboration, a comprehensive collection of controlled clinical trials from 1948 to the present. As a secondary source, we searched MEDLINE from 1966 to May 1998 to ensure completeness. Additionally, we used the related articles feature of PubMed, as well as recent search results submitted to the Baltimore Cochrane Center, the contents pages of recent relevant journals, and programs from recent cardiology meetings. Our search strategy included using the MeSH terms “atrial fibrillation” and “atrial flutter” as subject headings and text words, as well as “random allocation,” “double-blind method,” and “single-blind method.” The publication types were “randomized controlled trials” and “controlled clinical trials.”
Abstracts of the citations of randomized controlled clinical trials were reviewed independently by 2 members of the study team to identify articles that met the inclusion criteria. Only English-language articles were reviewed. However, we reviewed all English-language abstracts of non-English-language publications to assess qualitative consistency with our results.
