Washington University Emergency Medicine Journal Club- September 2020
Having recently returned from an extended (and entirely unexpected) six-week-long “staycation,” you return to work full of pep and vigor. During your first shift you encounter Mrs. Z, a sixty-five-year old woman with a history of mitral valve stenosis who presents with three days of palpitations and shortness of breath. Her symptoms began on Friday, but she decided to wait out the weekend and see her primary care doctor today (Monday). Her doctor did an ECG in the office and found her to be in new-onset atrial fibrillation with a rate in the 140s, so sent her to the ED for evaluation and treatment.
On arrival, her vitals are as follows:
HR 156 BP 136/83 RR 16 SpO2 98% T 36.8
She is well-appearing and in no distress. Cardiac exam reveals an irregularly irregular rhythm. Her lungs are clear. Lower extremity exam reveals no edema or calf tenderness. She reports that other than feeling her heart racing and noting shortness of breath on exertion she has no symptoms, including chest pain, syncope, and lightheadedness.
Since Mrs. Z has been having symptoms for more than 48 hours, she is not a candidate for urgent cardioversion, as previously discussed in journal club. After discussing with your attending, your plan is for anticoagulation and rate control. But which agent to use for rate control? You know from prior rotations that some seem to prefer metoprolol, but in your ED you have noticed that most attending use diltiazem almost exclusively. Wondering if there is a benefit to one agent over the other, you decide to do some digging and find a few relevant articles in the literature…
Population: Adult patients presenting to the emergency department in atrial fibrillation or atrial flutter with a rapid ventricular response without signs of hemodynamic compromise
Intervention: Bolused intravenous diltiazem
Comparison: Bolused intravenous metoprolol
Outcome: Frequency and time to rate control, ED length of stay, need for hospital admission, hypotension, bradycardia requiring urgent treatment
A PubMed search was performed using the terms “(atrial Bibrillation) OR (atrial
Blutter)) AND (metoprolol AND diltiazem)” resulting in 38 citations (https://
tinyurl.com/y6smse9t). An additional search of the Cochrane Database of Systematic Reviews revealed no additional evidence. The four most relevant articles from the
PubMed search were chosen for inclusion.
Article 1: Scheuermeyer FX, Grafstein E, Stenstrom R, et al. Safety and efBiciency of
calcium channel blockers versus beta-blockers for rate control in patients with atrial
Bibrillation and no acute underlying medical illness. Acad Emerg Med. 2013;20(3):
222-230. Answer Key.
Article 2: Fromm C, Suau SJ, Cohen V, 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;49(2):175-182. Answer Key.
Article 3: Nicholson J, Czosnowski Q, Flack T, Pang PS, Billups K. Hemodynamic
comparison of intravenous push diltiazem versus metoprolol for atrial Bibrillation
rate control. Am J Emerg Med. 2020;38(9):1879-1883. Answer Key.
Article 4: 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 Bibrillation [published correction appears in Emerg Med J.
2005 Oct;22(10):758]. Emerg Med J. 2005;22(6):411-414. Answer Key.
Atrial Bibrillation (AF) is the most common dysrhythmia encountered in the
emergency department (ED) and is responsible for over 500,000 visits in the United
States every year (Rozen 2018). Management options for patients with new-onset
AF with a rapid ventricular rate (RVR) in the ED typically include rhythm control
(via electrical or chemical cardioversion) and rate control. While several studies
have demonstrated similar outcomes among patients treated with these two
modalities (Wyse 2002, Chatterjee 2013), practice patterns in the US tend to favor
rate control and hospital admission. Rate control is most commonly accomplished
with beta-blocking agents or calcium-channel blocking agents, with IV metoprolol
or diltiazem recommended when urgent rate control is desired . Although there is no clear consensus on which agent is preferable in the ED population, there have been several studies addressing this question.
Early research comparing IV metoprolol with IV diltiazem in AF with RVR included a
small study comprised of 40 patients, randomized in a 1:1 fashion to the two
treatment arms (Demircan 2005). While patients assigned to IV diltiazem were
more likely to have “successful treatment” (reduction in ventricular rate to < 100
bpm or by 20% as long as the resulting rate was < 120 bpm) 2 minutes following
medication administration, success rates were similar at 5, 10, 15, and 20 minutes.
No patient converted to sinus rhythm during this time period and there was no
signiBicant difference in blood pressure change. These Bindings contrast with those
of a more recent randomized controlled trial from Maimonides Medical Center in
New York in which 54 patients were randomized, with 24 receiving IV diltiazem and
28 receiving IV metoprolol (Fromm 2015). In this study, a heart rate < 100 was achieved within 30 minutes of medication administration with much higher frequency in the diltiazem group, with a relative risk (RR) of 2.1 (95% CI 1.4 to 3.1). Both of the studies were primarily limited by the outcomes measures used; both studies looked at short-term rate control primarily (20 and 30 minutes, respectively) and neither looked at more patient-centered outcomes (e.g. ED length of stay or need for hospital admission). Given the time needed to obtain lab results
and perform consults, it is unlikely that rate control at 30 minutes would impact
Unfortunately, only observational studies have looked at these more relevant
outcomes, including a retrospective study conducted at two hospitals in Canada
(Scheuermeyer 2013) that enrolled patients with AF with RVR without a significant
underlying medical cause for AF. There was no significant difference in rates of
hospital admission between those receiving beta-blockers and calcium channel
blockers (27.0% vs. 31.0%; absolute difference 4.0%, 95% CI -7.7% to 16.1%).
Median ED length of stay was also similar in both patient groups, and there was no
difference in adverse outcomes.
While none of these studies demonstrated a signiBicant difference in blood pressure
decrease between patients receiving diltiazem and those receiving metoprolol, none
of these studies looked at blood pressure as a primary outcome. A recent
retrospective study (Nicholson 2020) did look at this, demonstrating a mean
reduction in systolic blood pressure (SBP) of 18±22 mmHg and 14±15 mmHg for the
diltiazem and metoprolol groups, respectively (p = 0.33). Furthermore, clinically
relevant hypotension occurred with similar frequency in the two groups (RR 0.92,
95% CI 0.37 to 2.3). Given the higher degree of negative inotropy associated with IV
metoprolol, there has been additional concern about its use in patients heart failure
with reduced ejection fraction. A retrospective study in this population (Hirschy
2019) found no difference in incidence of hypotension, bradycardia, or conversion,
with similar rate control efficacy.
Overall, these data demonstrate a more rapid reduction in heart rate with diltiazem
when compared with metoprolol in AF with RVR. While this does not seem to
translate into decreased ED length of stay or admission rate, this Binding comes from
a single retrospective study conducted in Canada, where admission rates for AF
seem to be much lower (28.6% compared to ~60% in US patients). Both
medications are reasonable options based on this review, though given the more
rapid reduction in heart rate with diltiazem, this may be a more prudent choice in
the busy emergency department where frequent reassessment may be difficult.