Evaluation of the blood pressure effects of diltiazem versus metoprolol in the acute treatment of atrial fibrillation with rapid ventricular rate

Design

Single-center, retrospective cohort study

N= 160

Objective

To evaluate the difference in blood pressure effects of diltiazem intravenous push (IVP) and metoprolol IVP in the acute management of atrial fibrillation with rapid ventricular rate (AF with RVR)

Study Groups

Diltiazem (n= 80)

Metoprolol (n= 80)

Inclusion Criteria

Aged ≥18 years, treated for AF with RVR or atrial flutter (AFL) with either diltiazem IVP or metoprolol IVP as the initial rate control agent, and had a baseline heart rate of ≥110 beats per minute (bpm)

Exclusion Criteria

Crossover of IVP agents used, received a different anti-arrhythmic or antihypertensive agent within 1 h of initial agent administration (including oral or continuous infusion); comorbidities or serious illnesses that may affect patient outcomes

Methods

Patients meeting inclusion criteria were grouped via initial rate control agent: diltiazem IVP or metoprolol IVP. Patients may receive repeat doses of the initial IVP agent if required.

Duration

Data collection: January 2012 to September 2018

60 ± 10 minutes

Outcome Measures

Primary: Median change in SBP at one hour

Secondary: Repeat doses, rate control to <110 bpm within 1 hour, lowest SBP within 3 hours, SBP <90 mmHg or ≤40% decrease within 3 hours

Baseline Characteristics

Diltiazem (n= 80)

Metoprolol (n= 80)

Median age, years

Female

Median weight, kg

Diagnosis

Atrial fibrillation with RVR

Atrial flutter with RVR

93%

9%

85%

20%

Results

Endpoint

Diltiazem (n= 80)

Metoprolol (n= 80)

p-value

Median change in SBP at 1 h, mmHg (IQR)

Doses

First dose, mg

Second dose, mg

Third dose, mg

17.5 (n= 80)

20 (n= 17)

-

5 (n= 80)

5 (n= 26)

5 (n= 11)

Repeat dose within 1 h

21%

33%

HR goal of <110 bpm achieved, n

At 1 h

At 3 h

54%

46%

43%

39%

0.205

0.424

Abbreviations: IQR= interquartile range

Adverse Events

N/A

Study Author Conclusions

In conclusion, diltiazem IVP versus metoprolol IVP result in similar blood pressure reduction for the acute management of AF with RVR. In patients presenting with an initial SBP < 110 mmHg, an increase in SBP may be seen. A larger prospective study is needed to further evaluate the difference on blood pressure effects in this patient population

InpharmD Researcher Critique

Limitations include the use of retrospective and observational data from a medical chart, as well as the small number of patients in each cohort. The study also did not meet the sample size required to achieve power, and thus may be too small to detect a difference between groups.

Hemodynamic comparison of intravenous push diltiazem versus metoprolol for atrial fibrillation rate control

Single-center retrospective study

N= 108 participants 

To determine if there was a significant difference in blood pressure reduction between intravenous push diltiazem and metoprolol for atrial fibrillation with rapid ventricular rate (RVR)

Diltiazem (n= 63)

Metoprolol (n= 45)

Adult patients (≥ 18 years) treated with IVP diltiazem or metoprolol for AF with RVR in the emergency department (ED)

Indication other than AF with RVR, known pregnancy, incarceration, prior rate or rhythm modifying interventions, extreme dosing, myocardial infarction during admission, SBP < 90 mmHg prior to intervention, fever ≥38°C, no BP documentation post-intervention, contraindications to diltiazem or metoprolol

Patient data were compiled via retrospective chart review from a single center in Indiana. Patients received IVP diltiazem or metoprolol based on clinician preference, patient presentation, or practice familiarity. Dosing strategies varied; metoprolol was given at a fixed dose while diltiazem was given as both fixed or weight-based.

Trial: patients treated between July 2008 to July 2018

Study period: from first dose to 30 min after last dose or first maintenance therapy

Extended study period: up to 6 hours after last IVP dose

Primary Outcome: Mean reduction in SBP from baseline to nadir

Secondary Outcomes: Clinically relevant hypotension, achievement of rate control

Age, years

Male

Weight, kg

31 ± 9

Past medical history

Atrial fibrillation

Congestive heart failure

38 (60%)

20 (32%)

39 (87%)

16 (36%)

0.095

0.68

146 ± 15

137 (125 to 148)

9 (14%)

12 (19%)

10 (10-20) mg or 0.14 (0.11 to 0.19) mg/kg

SBP reduction from baseline to nadir during study period, mmHg

SBP reduction from baseline to nadir during extended study period, mmHg

Hypotension composite

Fluid bolus

Nadir SBP < 90 mmHg

Vasopressor addition

Rate control composite

VR < 100 bpm

VR < 120 bpm if 20% reduction

35 (56%)

22 (35%)

13 (21%)

16 (36%)

10 (22%)

6 (13%)

Conversion to normal sinus rhythm

Clinically relevant hypotension was similar between groups (14% for diltiazem vs. 16% for metoprolol)

IVP diltiazem and metoprolol caused similar SBP reduction and hypotension when used for initial management of AF with RVR in the ED. However, rate control was achieved more often with diltiazem.

Strengths include a focus on hemodynamic outcomes and a clear comparison of two common treatments. Limitations include retrospective design, potential provider bias, and incomplete data due to missing documentation. The study was underpowered for the metoprolol group, and dosing strategies may have influenced outcomes.

Metoprolol vs. diltiazem in the acute management of atrial fibrillation in patients with heart failure with reduced ejection fraction

Design

Single-center, retrospective cohort study

N= 48

Objective

To examine the effects of metoprolol versus diltiazem in the acute management of atrial fibrillation (AF) with rapid ventricular response (RVR) in patients with heart failure with reduced ejection fraction (HFrEF)

Study Groups

Metoprolol (n= 14)

Diltiazem (n= 34)

Inclusion Criteria

Patients ≥ 18 years of age, treated for AF with RVR, documented EF ≤ 40%, HR ≥ 120 bpm, EF confirmed via echocardiogram within the previous five years

Exclusion Criteria

Pregnancy, pre-treatment SBP < 90 mm Hg, decompensated HF, crossover between treatment medications

Methods

Charts were retrospectively reviewed from a single-center in Illinois. Patients received intravenous push (IVP) doses of metoprolol or diltiazem in the emergency department. Common initial doses of metoprolol and diltiazem were 5 mg and 15 mg (IQR 10-20). If needed, a second dose could be administered at a dose of 5 mg metoprolol and 10 mg diltiazem within 30 min. 

Duration

Treated between January 2010 through September 2016

Outcome Measures

Primary: Successful rate control within 30 min (HR < 100 bpm or HR reduction ≥ 20%)

Secondary: Rate control at 60 min, maximum median change in HR, incidence of hypotension, bradycardia, conversion to normal sinus rhythm, signs of worsening heart failure

Baseline Characteristics

Metoprolol (n= 14)

Diltiazem (n= 34)

Age, years (interquartile range [IQR])

Female

Systolic blood pressure, mm Hg (IQR)

Heart rate, bpm (IQR)

Ejection fraction %, (IQR)

New York Heart Association Class 

I

II

III

IV

6 (43%)

3 (21%)

4 (29%)

1 (7%)

15 (44%)

7 (21%)

12 (35%)

0 (0%)

Home medications

ACE-inhibitor

Angiotensin receptor blocker

Beta-blocker

Calcium channel blocker

Digoxin

Amiodarone

Inotrope

Loop diuretic

9 (64%)

0 (0%)

14 (100%)

2 (14%)

4 (29%)

0 (0%)

0 (0%)

6 (43%)

15 (44%)

8 (24%)

23 (68%)

9 (26%)

2 (6%)

1 (3%)

0 (0%)

11 (32%)

Home loop diuretic dose, mg (IQR)

Past medical history

Atrial fibrillation

Asthma

COPD

Coronary artery disease

11 (79%)

2 (14%)

2 (14%)

10 (71%)

20 (59%)

4 (12%)

4 (12%)

13 (38%)

Rapid Emergency Medicine Score

Dose

Initial, mg (IQR)

Second, mg

Time between dose, min (IQR)

5

5

23 (12-23)

15 (10-20)

10

16 (8-30)

Results

Endpoint

Metoprolol (n= 14)

Diltiazem (n= 34)

p-value; Odds ratio (95% CI)

At 30 mins

Successful rate control

Heart rate, bpm

Hypotension

Bradycardia

Conversion

8/13 (62%)

114 (96–124)

0 (0%)

0 (0%)

0 (0%)

15/30 (50%)

110 (100−123)

1 (3%)

0 (0%)

2 (6%)

0.49; OR 0.63 (95%CI 0.17–2.36)

0.87

1.00

1.00

1.00

At 60 mins

Successful rate control

Heart rate, bpm

9 (64%)

110 (94–118)

16 (47%)

109 (99–120)

0.28; OR 0.49 (95%CI 0.14–1.78)

0.68

Transfer to an inpatient unit

Successful rate control

Heart rate, bpm

9 (64%)

111 (97–126)

21 (62%)

103 (92–114)

0.87; OR 0.90 (95%CI 0.25–3.27)

0.79

0.60

0.21; OR 3.00 (95%CI 0.63–14.27)

1.00

1.00

Increased O₂ requirement within 48 hours

Readmission within 7 days

Adverse Events

No significant difference in incidence of hypotension, bradycardia, or conversion to normal sinus rhythm was noted at 30 min between groups.

Study Author Conclusions

For the acute management of AF with RVR in patients with HFrEF, IVP diltiazem achieved similar rate control with no increase in adverse events when compared to IVP metoprolol.

InpharmD Researcher Critique

The study's strengths include its focus on a specific patient population and the comparison of two commonly used medications. However, limitations include its retrospective design, small sample size, lack of a formal treatment protocol, and potential selection bias due to differences in baseline characteristics. The study's findings may not be generalizable due to its single-center setting.

Diltiazem vs. Metoprolol in the Management of Atrial Fibrillation or Flutter with Rapid Ventricular Rate in the Emergency Department

Prospective, randomized, double-blind study

N= 52

To compare the effectiveness of diltiazem with metoprolol for rate control of atrial fibrillation/flutter in the emergency department (ED)

Diltiazem (n= 24)

Metoprolol (n= 28)

Adult patients aged 18 years or older presenting with atrial fibrillation or atrial flutter with a ventricular rate of ≥120 beats per minute (bpm) and a systolic blood pressure of ≥90 mm Hg

Systolic blood pressure (SBP) < 90 mm Hg, ventricular rate ≥ 220 bpm, QRS > 0.100 s, second- or third-degree antrioventricular (AV) block, temperature > 38.0°C, acute ST elevation myocardial infarction, NYHA Class IV heart failure, active wheezing with asthma or COPD, prehospital administration of diltiazem or AV nodal blockading agent, history of cocaine or methamphetamine use within 24 hours, allergic reaction to diltiazem or metoprolol, sick sinus or pre-excitation syndrome, anemia with hemoglobin < 11.0 g/dL, pregnancy, or breastfeeding

Adult ED patients meeting inclusion criteria were randomized 1:1 to receive blinded IV diltiazem or IV metoprolol. Initial diltiazem dose was 0.25 mg/kg, maximum 30 mg; initial metoprolol dose was 0.15 mg/kg, maximum 10 mg. If heart rate (HR) <100 beats/min was not achieved at 15 minutes, a second blinded escalation dose was administered: diltiazem 0.35 mg/kg, maximum 30 mg, or metoprolol 0.25 mg/kg, maximum 10 mg. HR, SBP, and diastolic blood pressure (DBP) were monitored at baseline and at 5, 10, 15, 20, 25, and 30 minutes after drug administration. Enrollment was stopped early after safety monitoring found that significantly more patients in one group were reaching the desired endpoint.

June 2009 to November 2010

Primary: HR < 100 bpm within 30 min

Secondary: Safety outcomes (hypotension and bradycardia)

Diltiazem (n= 24)

66.2 ± 13.4

46.9

20.8%

21.0%

132.4 ± 23.8

88.7 ± 19.4

136.8 ± 15.3

4.0%

29.2%

8.0%

25.0%

70.8%

Abbreviation: COPD, chronic obstructive pulmonary disease.

Diltiazem (n= 24)

50.0%

95.8%

4.2

Mean baseline heart rate was similar between groups (136.8 beats/min with diltiazem vs 142.2 beats/min with metoprolol; p= 0.231).

By 5 minutes, mean heart rate decreased to 102.1 beats/min with diltiazem versus 127.3 beats/min with metoprolol (p= 0.0001), and this between-group difference persisted through 10 minutes (98.0 vs 121.7 beats/min; p= 0.0001), 15 minutes (95.6 vs 117.6 beats/min; p= 0.001), 20 minutes (90.8 vs 116.9 beats/min; p= 0.0001), 25 minutes (90.9 vs 113.5 beats/min; p= 0.0001), and 30 minutes (90.3 vs 115.6 beats/min; p= 0.0001).

In multivariable Cox regression controlling for age, sex, baseline heart rate, baseline systolic and diastolic blood pressure, and adenosine administration, patients receiving diltiazem were significantly more likely to achieve HR <100 beats/min within 30 minutes compared with metoprolol (hazard ratio 4.657; 95% confidence interval [CI] 2.093-10.363; p= 0.0001).

No difference between groups with respect to hypotension (SBP < 90 mm Hg) and bradycardia (HR< 60 bpm)

Diltiazem was more effective than metoprolol in achieving rate control in ED patients with AFF at all time points within 30 min and did so with no increased incidence of adverse effects.

This randomized, double-blind ED study directly addresses the inquiry and found faster and more frequent achievement of HR <100 beats/min with IV diltiazem compared with IV metoprolol over 30 minutes, without a statistically significant increase in hypotension or bradycardia. However, interpretation is limited by the small sample size, early termination, convenience sampling, restricted enrollment hours, and use of a capped metoprolol dosing strategy that the authors noted may have influenced efficacy and safety outcomes.

Efficacy and Safety of Diltiazem versus Metoprolol in the Management of Atrial Fibrillation with Rapid Ventricular Response

Retrospective cohort study using the TriNetX database

N= 14,598

To evaluate whether intravenous (IV) diltiazem or IV metoprolol is more efficacious in managing atrial fibrillation with rapid ventricular response by examining outcomes of patient mortality, heart rate (HR) control, and intensive care unit (ICU) admissions

IV diltiazem (n= 7,299)

IV metoprolol (n= 7,299)

Adult patients aged 18 years and older diagnosed with paroxysmal or unspecified atrial fibrillation with a heart rate of at least 150 bpm, treated with either IV diltiazem or IV metoprolol between September 22, 2003, and September 22, 2023

Patients whose indexed event occurred more than 20 years ago

Data were obtained from the TriNetX U.S. Collaborative Network, which included nearly 92 million patients across 59 healthcare organizations, primarily large academic tertiary care centers and associated satellite facilities in the United States. Adult patients with atrial fibrillation and heart rate ≥150 beats/min were identified using ICD-10-CM, RxNorm, and TriNetX codes. Cohort 1 included patients given IV diltiazem without metoprolol on the same day as atrial fibrillation diagnosis, and cohort 2 included patients given IV metoprolol without diltiazem on the same day as atrial fibrillation diagnosis. Outcomes were evaluated from 1 to 7 days after diagnosis and treatment. A 1:1 propensity score matching analysis was performed using demographics and comorbidities associated with mortality, including age, sex, race/ethnicity, hypertension, diabetes, acute and chronic renal failure, obesity, heart failure, prior cardiac arrest, ischemic heart disease, and malignant neoplasm of the bronchus/lung. Statistical analyses were performed before and after propensity matching, with statistical significance defined as a 2-sided alpha <0.05.

September 22, 2003, to September 22, 2023

Primary: 7-day mortality rate, myocardial infarction rates, heart rate control, ICU admissions

IV metoprolol (n= 7,299)

66.3 ± 13.2

77.9%

46.1%

63.3%

26.7%

24.7%

IV diltiazem

3.3%

2.4%

35.7%

13.4%

Not specifically detailed in the provided text.

IV diltiazem showed superiority in reducing mortality, heart rate control, and decreased ICU admissions over IV metoprolol for managing A-fib with RVR. This data supports the preferential use of IV diltiazem for A-fib with RVR.

The study's large sample size and use of propensity score matching are strengths, enhancing the reliability of the findings. However, as a retrospective study, it cannot establish causation, and potential confounders not accounted for in the analysis may influence results. The lack of detailed information on treatment duration and dose appropriateness is a limitation. Additionally, the inability to assess clustering of treatment at specific centers due to data privacy policies limits the analysis.

Intravenous Metoprolol Versus Diltiazem for Rate Control in Atrial Fibrillation

Single-center, retrospective cohort study

N= 200

To compare the efficacy and safety of intravenous (IV) metoprolol and diltiazem for rate control

Metoprolol (n= 100)

Diltiazem (n= 100)

Patients 18 years or older, presented to the emergency department (ED) between 2015 and 2019 with atrial fibrillation (AF) with rapid ventricular response (RVR), and received either IV metoprolol or diltiazem within 1 hour

Patients who were pregnant, incarcerated, or had an implanted pacemaker or cardioverter-defibrillator

Retrospective review of medical records for patients who received IV metoprolol or diltiazem. Rate control defined as heart rate (HR) < 100 beats per minute (bpm) within 2 hours. Data collected included demographics, clinical data, and outcomes such as time to rate control and adverse events.

2015 to 2019

Primary: Percentage of patients achieving rate control (HR < 100 bpm within 2 hours)

Secondary: Time to rate control, percentage requiring additional agents, incidence of cardioversion, bradycardia, and hypotension

Age, years (IQR)

Female

Baseline heart rate, beats per minute (IQR)

Prior to admission medication

None

β-blocker

Nondihydropyridine calcium channel blocker

10 (10%)

88 (88%)

2 (2%)

37 (37)

56 (56)

13 (13)

<0.001

<0.001

0.003

Hypertension

Diabetes

Heart failure

Heart failure with ejection fraction ≤ 40%

Abbreviations: IQR, interquartile range.

Overall rate control

Time to rate control, minutes (IQR)

Cardioversion

Hypotension

Bradycardia

One patient developed hypotension, no patient developed bradycardia, and 4 patients required electric cardioversion. No adverse events were observed in patients with ejection fraction ≤40%.

There was no difference in the achievement of rate control between IV metoprolol and diltiazem. This is the largest study to date comparing the two classes of agents for acute rate control in AF. No patient-specific factors were identified that would influence the preferential use of one medication over the other.

This study directly addresses the inquiry because it evaluated adult ED patients with AF with RVR who received IV metoprolol or IV diltiazem, and it found no statistically significant difference in achievement of rate control within 2 hours. Interpretation is limited by the retrospective, single-center design; nonstandardized treatment selection and dosing; significant baseline differences in prior rate-control medication use; and lack of follow-up beyond 2 hours, which limits conclusions about sustained rate control.

Comparison of the Effectiveness of Intravenous Diltiazem and Metoprolol in the Management of Rapid Ventricular Rate in Atrial Fibrillation

Prospective, double-blind, randomised study

N= 40

To compare the effectiveness of intravenous (IV) diltiazem and metoprolol in the management of rapid ventricular rate in atrial fibrillation (AF)

Diltiazem (n= 20)

Metoprolol (n= 20)

Patients >18 years of age with AF, ventricular rate >120/minute, and systolic blood pressure >95 mm Hg

History of allergic reactions to diltiazem and metoprolol, congestive heart failure (NYHA Class IV), systolic blood pressure <95 mm Hg, sick sinus syndrome, AV block (2nd or 3rd degree), pre-excitation syndromes, ventricular rate >220/min, QRS >0.08 s, unstable angina pectoris, acute myocardial infarction, hyperthyroidism, temperature >38.0 ˚C, haemoglobin <11.0 g/dl, bronchial asthma, COPD, diabetes mellitus, peripheral vascular disease, pregnancy, recent use of diltiazem, verapamil, digoxin, b blockers, theophylline, or b mimetics within the last five days

Patients presenting to the emergency department with atrial fibrillation and rapid ventricular rate were randomized using sealed opaque envelopes to receive either IV diltiazem 0.25 mg/kg, maximum 25 mg, or IV metoprolol 0.15 mg/kg, maximum 10 mg. Both medications were administered over 2 minutes by ED nursing staff, with the injection volume equalized using normal saline. A blinded observer measured heart rate using a rhythm strip of at least 30 seconds and recorded blood pressure at baseline and at 2, 5, 10, 15, and 20 minutes after treatment. Successful treatment was defined as ventricular rate <100/min, ≥20% decrease in ventricular rate with rate <120/min, or conversion to sinus rhythm. If initial therapy was unsuccessful, IV diltiazem rescue therapy was given at the end of the 20-minute study period.

January 2000 to July 2002

Treatment success at 2, 5, 10, 15, and 20 minutes; ventricular rate at each time point; percentage decrease in ventricular rate at each time point; blood pressure changes at each time point; hypotension, defined as systolic blood pressure <90 mm Hg

Diltiazem (n= 20)

60.2

12

156.4

IV diltiazem produced a greater reduction in ventricular rate than IV metoprolol at all assessed time points through 20 minutes.

Mean ventricular rate decreased from 156.4 to 100.0 beats/min with diltiazem and from 152.0 to 107.5 beats/min with metoprolol at 20 minutes; corresponding mean percentage decreases in ventricular rate were significantly greater with diltiazem at 2 minutes (25.6% vs 17.5%; p< 0.05), 5 minutes (30.7% vs 20.4%; p< 0.01), 10 minutes (33.6% vs 24.3%; p< 0.01), 15 minutes (34.5% vs 25.9%; p< 0.01), and 20 minutes (35.9% vs 28.9%; p< 0.05).

Treatment success was significantly higher with diltiazem at 2 minutes (50% vs 15%; p< 0.05), but differences were not statistically significant at 5, 10, 15, or 20 minutes; by 20 minutes, success occurred in 90% of diltiazem-treated patients and 80% of metoprolol-treated patients (p> 0.05).

No patients converted to sinus rhythm, and no hypotension occurred in either treatment group.

None of the patients had hypotension.

Both diltiazem and metoprolol were safe and effective for the management of rapid ventricular rate in AF. However, the rate control effect began earlier and the percentage decrease in ventricular rate was higher with diltiazem than with metoprolol.

The study was well-designed with a double-blind, randomised approach, providing reliable results. However, the small sample size and single-center setting may limit the generalizability of the findings. Additionally, the study did not include a comparison with other rate control agents such as digoxin or verapamil.