Atrial Fibrillation Rate Control in the ED: Calcium Channel Blockers or Beta Blockers?

Rate control with IV medications is recommended for atrial fibrillation in the acute setting in patients without preexcitation. This was a Class 1 recommendation (Level of Evidence B) per the 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation [1]. What does the evidence say? Are calcium channel blockers or beta blockers better?

Esmolol vs. Verapamil [2]

45 patients (21 got esmolol, 24 got verapamil). Atrial fibrillation or atrial flutter. Randomized, parallel, open-label study. Heart rate declined with esmolol from 139 to 100 beats/min (p < 0.001) and with verapamil from 142 to 97 beats/min (p < 0.001). Fifty percent of esmolol-treated patients with new onset of arrhythmias converted to sinus rhythm, whereas only 12% of those who received verapamil converted (p < 0.03). Mild hypotension was observed in both treatment groups.

Take Home: Esmolol and verapamil both lowered heart rate effectively. More new onset cases converted to sinus rhythm with esmolol.

 

Metoprolol vs. Diltiazem [3]

40 patients (20 got metoprolol, 20 got diltiazem). Atrial fibrillation. Prospective, randomized study in the ED. IV diltiazem 0.25 mg/kg (maximum 25 mg) or metoprolol 0.15 mg/kg (maximum 10 mg) over 2 minutes. Successful treatment was defined as fall in ventricular rate to below 100/minute, decrease in ventricular rate by 20%, or return to sinus rhythm. The success rate at 20 minutes for diltiazem and metoprolol was 90% (n = 18) and 80% (n = 16), respectively (p > 0.05). The success rate at 2 minutes was higher in the diltiazem group (50% vs. 15%, p < 0.05). The percentage decrease in ventricular rate was higher in the diltiazem group at each time interval. None of the patients had hypotension.

Take Home: Metoprolol and diltiazem both lowered heart rate effectively. Diltiazem may have fared slightly better.

 

Metoprolol vs. Diltiazem [4, 10]

52 patients (28 got metoprolol, 24 got diltiazem). Atrial fibrillation or atrial flutter. Prospective, randomized, double-blind trial in the ED. Primary outcome was HR < 100. Diltiazem dose was 0.25 mg/kg (max 30 mg), metoprolol dose was 0.15 mg/kg (max 10 mg). A second dose was allowed after 15 minutes if the primary outcomes was not achieved. Within 30 minutes, 95.8% in the diltiazem vs. 46.4% in the metoprolol group reached target heart rate < 100 bpm (p < 0.0001). In the first 5 minutes, 50% in the diltiazem vs. 10.7% in the metoprolol group reached heart rate control (p < 0.005). No patients required cardioversion.

This is the highest quality study comparing these two drugs, yet it still has some important limitations. First, it was a convenience sample. Second, the max dose of metoprolol was 10 mg. Many institutions use a 5 mg X 3 approach for a total of 15 mg. Therefore, this may not be a fair comparison. The authors also didn’t comment on how many patients in either group required a second dose of the assigned medication. Third, I’m also wondering why it took 4 years to get this study published after its presentation at the 2011 SAEM annual meeting.

Take Home: Diltiazem lowered HR more effectively than metoprolol at all time points up to and including 30 minutes, though the metoprolol dose may have been too low.

 

Calcium Channel Blocker vs. Beta Blocker [5]

This prospective study actually looked at rates of cardioversion in new onset atrial fibrillation or atrial flutter in the ED, but also included data on rate control. 206 total patients (109 patients had rate control data documented). Rate control success was 71% for calcium channel blockers and 79% for beta blockers (statistics not reported). Two patients that received diltiazem had hypotension reported as an adverse effect.

Take Home: Both calcium channel blockers and beta blockers were effective in controlling heart rate, but the medications and doses used were not reported.

 

Calcium Channel Blocker vs. Beta Blocker [6]

259 patients (100 got CCBs, 159 got BBs). Atrial fibrillation. Retrospective cohort of ED patients. The objective was to determine whether beta blockers or calcium channel blockers would have a lower hospital admission rate and to measure 30-day safety outcomes including stroke, death, and ED revisits. 27% of beta blocker patients and 31.0% of calcium channel blocker patients were admitted (95% CI = -7.7% to 16.1%), and there were no significant differences in ED LOS, adverse events, or 7- or 30-day ED revisits.

Take Home: Calcium channel blockers had similar hospital admission rates to those receiving beta blockers, while both classes of medications appeared equally safe at 30 days.

 

What does it all mean?

From an ED standpoint, both CCBs and BBs appear to be effective. The highest quality study seemed to demonstrate that diltiazem performed better than metoprolol, though the metoprolol dose may have been too low [4, 10]. Previous thinking suggested that diltiazem reduced the probability of spontaneous conversion of atrial fibrillation to normal sinus rhythm. However, a prospective, randomized study found this notion to be false [7]. A major limitation of the studies to date is the heterogeneity of the populations enrolled, as it is unclear how calcium channel blockers or beta blockers might perform in patients with certain comorbidities. These considerations may be important clinically, as calcium channel blockers or beta blockers may not be ideal in certain scenarios (e.g., CCBs in patients with heart failure or BBs in patients with reactive airway disease). A similarly important limitation is whether a change in heart rate should serve as the major determinant efficacy or whether a more clinically meaningful outcome (e.g., length of stay, need for direct current cardioversion) may be more ideal.

In part 2 of our two-part series, my cardiology pharmacist colleague, Brent Reed, PharmD, FAHA (@brentnreed), explores the ED’s choice of calcium channel blockers or beta blockers and its effect on chronic management choices by the inpatient team: Thinking Beyond the Emergency Department.

Update: January 2015

A new systematic review published online January 2, 2015 identified two randomized, double blind trials comparing diltiazem to metoprolol for acute rate control. [8] One of the trials is discussed above. [3] The other was an abstract published in 2011. [9] With only two trials to work from, the systematic review found the combined relative risk of acute rate control by diltiazem versus metoprolol was 1.8 (95% confidence interval 1.2-2.6).

Update: April 2015

The abstract presented at the 2011 Society for Academic Emergency Medicine Annual Meeting  [4], was published online as a peer-reviewed manuscript [10]. Updated analysis of this study is discussed above.

References

1. January CT, Wann LS, Alpert JS, et al. 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society. Circulation 2014;130(23):e199-267. PMID: 24682347 [PDF, 7.1 MB]
2. Platia EV, Michelson EL, Porterfield JK, Das G. Esmolol versus verapamil in the acute treatment of atrial fibrillation or atrial flutter. Am J Cardiol 1989;63(13):925-9. PubMed PMID: 2564725.
3. Demircan C, Cikriklar HI, Engindeniz Z, et al. Comparison of the effectiveness of intravenous diltiazem and metoprolol in the management of rapid ventricular rate in atrial fibrillation. Emerg Med J 2005;22(6):411-4. Erratum in: Emerg Med J 2005;22(10):758.  PubMed PMID: 15911947.
4. Abstracts of the SAEM (Society for Academic Emergency Medicine) Annual Meeting. June 1-5, 2011. Boston, Massachusetts, USA. Acad Emerg Med 2011;18 Suppl 1:S1-268. Abstract 616. PubMed PMID: 21598455.
5. Vinson DR, Hoehn T, Graber DJ, Williams TM. Managing emergency department patients with recent-onset atrial fibrillation. J Emerg Med 2012;42(2):139-48. PubMed PMID: 20634022.
6. Scheuermeyer FX, Grafstein E, Stenstrom R, et al. Safety and efficiency of calcium channel blockers versus beta-blockers for rate control in patients with atrial fibrillation and no acute  underlying medical illness. Acad Emerg Med 2013;20(3):222-30. PubMed PMID: 23517253.
7. Hassan S, Slim AM, Kamalakannan et al. Conversion of atrial fibrillation to sinus rhythm during treatment with intravenous esmolol or diltiazem: a prospective, randomized comparison. J Cardiovasc Pharmacol Ther 2007;12(3):227-31. PubMed PMID: 17875950.
8. Martindale JL, et al. Beta-blockers versus calcium channel blockers for acute rate control of atrial fibrillation with rapid ventricular response: a systematic review. Eur J Emerg Med 2015;22(3):150-4. PubMed PMID: 25564459.
9. Fromm C, et al. Comparison of diltiazem and metoprolol in the management of atrial fibrillation or flutter with rapid ventricular rate in the emergency department: a prospective, randomized double-blind trial [abstract]. Emerg Med J 2011;18 (Suppl 1):235.
10. Fromm C, et al. Diltiazem vs. Metoprolol in the Management of Atrial Fibrillation or Flutter with Rapid Ventricular Rate in the Emergency Department. J Emerg Med. 2015 Apr 22. [Epub ahead of print]

Original June 4, 2014; updated April 23, 2015

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