Clinical Question:

A 68-year-old woman presents to the emergency room and she mentions that she feels heart palpitations, dizziness, and shortness of breath. The patient is hemodynamically stable with her heart rate at 142 beats per minute. A stat EKG is done and it shows the patient is having atrial fibrillation with rapid ventricular rate. The nurse asks the provider which medication should be administered, diltiazem or metoprolol.

Search Question:

In adults with atrial fibrillation with rapid ventricular rate, how does IV diltiazem compare to IV metoprolol in terms of time to achieve rate control and reducing incidences of hypotension and bradycardia?

PICO Question:

P	I	C	O
Adults with A-Fib	Intravenous Diltiazem	Intravenous Metoprolol	Rate control achieved
A-Fib	Diltiazem	Metoprolol	Reducing incidence of hypotension
Atrial Fibrillation			Reducing incidence of bradycardia
Atrial Fibrillation with Rapid Ventricular Rate

Search Strategy:

PubMed

• Atrial fibrillation AND Diltiazem – 22 articles
  • Filters: last 10 years
• Atrial fibrillation AND Diltiazem AND Metoprolol – 14 articles
  • Filters: last 10 years
• Atrial fibrillation with rapid ventricular rate AND Diltiazem AND Metoprolol – 8 articles
  • Filters: last 10 years

TRIP Database

• (Atrial fibrillation) (Diltiazem) – 68 articles
  • Filter: last 10 years
• (Atrial fibrillation) (Diltiazem) (Metoprolol) – 14 articles
  • Filter: last 10 years

Cochrane Library

• (Atrial fibrillation) (Diltiazem) (Metoprolol) – 26 articles
  • Filter: Last 10 years
• (Atrial fibrillation with rapid ventricular rate) (Diltiazem) (Metoprolol) – 2 articles
  • Filter: Last 10 years

For the article selection of my Mini-CAT I wanted to find articles that were of the highest level of evidence available, which were either a systematic review or a meta-analysis. I looked for studies that were within that last ten years, but thankfully the five articles I chose were all within the last five years making them very recent and topical.

I searched through 3 different databases and I ended up choosing my five articles from PubMed and Trip Database. I included one systematic reviews/meta-analysis, one meta-analysis, and three retrospective cohort studies. I wanted to include some real-world American studies in my Mini-CAT because I wanted to see if the data mirrored the same information as the systematic reviews/meta-analysis and I was curious in seeing how emergency rooms were running their own codes like an A-Fib with RVR.

Articles Chosen (5 or more) for Inclusion:

1) Lan, Q., Wu, F., Han, B., Ma, L., Han, J., & Yao, Y. (2022). Intravenous diltiazem versus metoprolol for atrial fibrillation with rapid ventricular rate: A meta-analysis. The American Journal of Emergency Medicine, 51, 248–256. https://doi.org/10.1016/j.ajem.2021.08.082

Abstract

Background: Intravenous diltiazem and metoprolol are both commonly used to treat atrial fibrillation (AF) with rapid ventricular rate (RVR) in the emergency department (ED), but the advantages and disadvantages of these drugs cannot be verified. This meta-analysis aimed to assess the efficacy and safety of intravenous diltiazem versus metoprolol for AF with RVR.

Method: We systematically searched PubMed, Web of Science, Embase, Cochrane library, the China National Knowledge Infrastructure (CNKI), Wanfang, China Biology Medicine disc (CBM) and the WeiPu (VIP). Meta-analysis was performed using weighted mean difference (WMD), relative risk (RR) and 95% confidence interval (CI). Statistical analysis was performed using Review Manager 5.4.1.

Results: Seventeen studies involving 1214 patients in nine randomized controlled trials (RCTs) and eight cohort studies were included in meta-analysis, including 643 patients in the intravenous diltiazem group and 571 patients group in the intravenous metoprolol. The results of the meta-analysis showed that compared with intravenous metoprolol, intravenous diltiazem was found higher efficacy (RR =1.11; 95% CI = 1.06 to 1.16, p < 0.00001), shorter average onset time (RR = −1.13; 95% CI = −1.97 to −0.28, p = 0.009), lower ventricular rate (RR = −9.48; 95% CI = −12.13 to −6.82, p<0.00001), less impact on systolic blood pressure (WMD = 3.76; 95% CI: 0.20 to 7.33, P = 0.04), and no significant difference in adverse events (RR = 0.80, 95% CI = 0.55 to 1.14, P = 0.22) and diastolic blood pressure (WMD = −1.20; 95% CI: −3.43 to 1.04, P = 0.29) was found between intravenous diltiazem and metoprolol.

Conclusion: Intravenous diltiazem has higher efficacy, shorter average onset time, lower ventricular rate, less impact on blood pressure, and with no increase in adverse events compared to intravenous metoprolol.

https://www-sciencedirect-com.york.ezproxy.cuny.edu/science/article/pii/S0735675721008883?via%3Dihub

2) Sharda, S. C., & Bhatia, M. S. (2022). Comparison of diltiazem and metoprolol for atrial fibrillation with rapid ventricular rate: Systematic review and meta-analysis. Indian Heart Journal, 74(6), 494–499. https://doi.org/10.1016/j.ihj.2022.10.195

Abstract

Background: Intravenous calcium channel blockers or beta-blockers are the preferred rate control medications for hemodynamically stable patients with atrial fibrillation with rapid ventricular rate (AF-RVR) in the emergency department.

Objectives: To compare the efficacy of intravenous diltiazem and metoprolol for rate control and safety with respect to development of hypotension and bradycardia in patients with AF-RVR.

Methods: For this systematic review and meta-analysis, we searched PubMed, Embase, Cochrane databases, and the clinicaltrials.gov registry between database inception and 30th May 2021. Articles were included if they compared efficacy and safety of diltiazem versus metoprolol in critically ill adult patients hospitalized with AF-RVR. Outcome measures were achievement of rate control, development of new hypotension, and bradycardia after drug administration.

Results: Of 86 records identified, 14 were eligible, all of which had a low to moderate risk of overall bias. The meta-analysis (Mantel-Haenszel, random-effects model) showed that diltiazem use was associated with increased achievement of rate control target compared to metoprolol [14 studies, n = 1732, Odds Ratio (OR): 1.92; 95% Confidence Intervals (CI):1.26 to 2.90; I2 = 61%]. In the pooled analysis, no differences were seen in hypotension using diltiazem vs metoprolol [12 studies, n = 1477, OR: 0.96; 95% CI:0.61 to 1.52; I2 = 35%] or bradycardia [9 studies, n = 1203, OR: 2.44; 95% CI: 0.82 to 7.31; I2 = 48%].

Conclusions: Intravenous diltiazem is associated with increased achievement of rate control target in patients with AF-RVR compared to metoprolol, while both medications are associated with similar incidence of hypotension and bradycardia.

https://www.sciencedirect.com/science/article/pii/S001948322200356X?via%3Dihub

3) Blackburn, M., Edwards, L., Woolum, J., Bailey, A., Dugan, A., & Slade, E. (2023). Metoprolol versus diltiazem in the emergency department for atrial fibrillation with rapid ventricular response. JEM Reports, 2(2), 100020-. https://doi.org/10.1016/j.jemrpt.2023.100020

Abstract

Background: Atrial fibrillation (Afib) is the most commonly treated arrhythmia in the Emergency Department (ED). Multiple guidelines recommend the use of intravenous (IV) beta-blocking (BB) agents or nondihydropyridine calcium channel blockers (Non-DHP CCB) as first line agents for heart rate control. Data regarding optimal first line selection between the agents is lacking.

Objectives: The primary objective was to determine whether a clinically significant difference exists in achieving rate control and time to rate control between use of IV metoprolol or diltiazem.

Methods: This was a dual center, retrospective, cohort, chart review of patients presenting to the ED from January 1, 2015 to March 1, 2020, who received either IV bolus doses of metoprolol or diltiazem for Afib with RVR. Inclusion criteria: ≥18 years of age, received a bolus dose(s) of IV metoprolol or diltiazem for management in the ED, and ECG confirmed diagnosis of Afib based on ICD 9/10 codes.

Results: Analyzed 305 patients with 99 patients in the metoprolol group and 206 patients in the diltiazem group. The primary outcome of time to HR ​< ​110 bpm was not statistically significant between metoprolol and diltiazem groups. Rates of adverse events including bradycardia and hypotension were not significantly different.

Conclusion: There was no significant difference in the time to adequate heart rate control following administration of IV metoprolol or diltiazem for the treatment of atrial fibrillation with rapid ventricular response.

https://www.sciencedirect.com/science/article/pii/S2773232023000160

4) McGrath, P., Kersten, B., Chilbert, M. R., Rusch, C., & Nadler, M. (2021). Evaluation of metoprolol versus diltiazem for rate control of atrial fibrillation in the emergency department. The American Journal of Emergency Medicine, 46, 585–590. https://doi.org/10.1016/j.ajem.2020.11.039

Abstract

Objective: The purpose of this study was to compare the effectiveness and safety of the metoprolol and diltiazem administration in the Emergency Department (ED) for rate control of supraventricular tachycardia.

Methods: This was a retrospective cohort study of adult patients who presented to the ED with ventricular rates ≥120 beats per minute (bpm) and who received bolus doses of either intravenous metoprolol or intravenous diltiazem. The primary outcome was achievement of rate control, defined as heart rate < 110 bpm, at two hours after administration of the last bolus dose of metoprolol or diltiazem. Safety outcomes included occurrence of hypotension, defined as systolic blood pressure < 90 mmHg or diastolic blood pressure < 60 mmHg, and bradycardia, defined as heart rate < 60 bpm.

Results: There were 166 patients receiving metoprolol and 183 patients receiving diltiazem included in the study. The primary outcome, rate control at two hours after the last bolus dose of metoprolol or diltiazem was similar between the two groups (45.8% vs 42.6%, p = 0.590, respectively). The percentage of patients achieving rate control was also similar (47.0% vs 41.6%, p = 0.333) at one hour. At 0.5 h HR had a significantly greater numerical (diltiazem: 29.3 ± 23.1 bpm vs metoprolol: 21.8 ± 18.9 bpm, p = 0.012) and percent decrease (21.1% vs 15.94%, p = 0.014) in the diltiazem group compared to metoprolol. There was no significant difference in occurrence of bradycardia in the two groups (diltiazem: 3.83% vs metoprolol: 1.2%, p = 0.179). More patients in the diltiazem group compared to the metoprolol group experienced hypotension (39.3% vs 23.5%, p = 0.002). The difference in systolic hypotension events was not significantly different (9.29% vs 5.42%, p = 0.221), while the difference in diastolic hypotension events was significantly different (37.7% vs 22.3%, p = 0.002).

Conclusion: There was no difference in acute rate control effectiveness two hours after the last bolus dose of diltiazem and metoprolol for supraventricular tachycardias. There was a significantly higher occurrence of hypotension in the diltiazem group which was driven by higher rates of diastolic blood pressures less than 60 mmHg.

https://www-sciencedirect-com.york.ezproxy.cuny.edu/science/article/pii/S0735675720310639?via%3Dihub

5) Nicholson, J., Czosnowski, Q., Flack, T., Pang, P. S., & Billups, K. (2020). Hemodynamic comparison of intravenous push diltiazem versus metoprolol for atrial fibrillation rate control. The American Journal of Emergency Medicine, 38(9), 1879–1883. https://doi.org/10.1016/j.ajem.2020.06.034

Abstract

Objective: Intravenous push (IVP) diltiazem and metoprolol are commonly used for management of atrial fibrillation (AF) with rapid ventricular rate (RVR) in the emergency department (ED). This study’s objective was to determine if there was a significant difference in blood pressure reduction between agents.

Methods: This was a single-center, retrospective study of adult patients initially treated with IVP diltiazem or metoprolol in the ED from 2008 to 2018. Primary endpoint was mean reduction in systolic blood pressure (SBP) from baseline to nadir during the study period. Study period was defined as time from first dose of IVP intervention to 30 min after last dose of IVP intervention or first dose of maintenance therapy, whichever came first.

Results: A total of 63 diltiazem patients and 45 metoprolol patients met eligibility criteria. Baseline characteristics were similar except for initial ventricular rate (VR) and home beta-blocker use. Median dose of initial intervention was 10 [10−20] mg and 5 [5–5] mg for diltiazem and metoprolol respectively. Mean SBP reduction was 18 ± 22 mmHg for diltiazem compared to 14 ± 15 mmHg for metoprolol (p = .33). Clinically relevant hypotension was similar between groups 14% vs. 16% (p = .86). Rate control was achieved in 35 (56%) of the diltiazem group and 16 (36%) of the metoprolol group (p = .04).

Conclusion: 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.

https://www-sciencedirect-com.york.ezproxy.cuny.edu/science/article/pii/S0735675720305222?via%3Dihub

Summary of the Evidence:

Author (Date)	Level of Evidence	Sample/Setting (# of subjects/ studies, cohort definition etc)	Outcome(s) studied	Key Findings	Limitations and Biases
Qingsu, L.; Fengchao, W.; Bing, H.; Lanhu, M.; Junxia, H.; Yali, Y. (2022)	Meta-Analysis	– 17 studies were included involving 1,214 patients in nine RCTs and eight cohort studies   – 643 patients were in the IV Diltiazem group   – 571 patients were in the IV Metoprolol group	– Primary outcomes studied were medication efficacy, average onset time, ventricular rate impact on blood pressure and adverse effects     Tool Used: – RevMan 5.4.1 software	– For efficacy, the results showed that IV diltiazem was superior than IV metoprolol   – The results showed that IV diltiazem had an average onset time that was shorter than IV metoprolol   – IV diltiazem was better than IV metoprolol in decreasing ventricular rate than IV metoprolol   – There were no statistical differences in regards to hypotension or adverse events for either diltiazem or metoprolol	– The sample size of the meta-analysis was not the largest that could have been used   – There might have been some selective or implication bias in the trial designs because some of the studies did not specifically mention their random sampling methods
Saurabh, S., & Mandip, B. (2022)	Systematic Review and Meta-Analysis	– 14 studies were included in this systematic review/meta-analysis with three RCTs and eleven retrospective studies   – There was a total of 1,732 patients who were treated for A-Fib with RVR   – 773 patients were treated with IV Diltiazem   – 959 patients were treated with IV Metoprolol	– The primary outcome looked at the efficacy between IV diltiazem and IV metoprolol for rate control   – Secondary outcomes looked at any adverse effects that may have arisen from giving either drug with respect to the development of new hypotension or bradycardia   Statistical analysis was preformed using RevMan version 5.4 software	– Regarding the primary outcome, patients treated with IV diltiazem had significantly greater achievement of rate control target compared to patients treated with IV metoprolol   – There were no significant differences between administering either drug for the occurrences of hypotension or bradycardia	– The biggest limitation from this study was that it only had three randomized control trials to gather information from, while the rest of the information was taken from retrospective studies   – Factors like re-admission rates, 30-day mortality rates and patients who may have had worsening heart failure were excluded in the study
Blackburn, M., Edwards, L., Woolum, J., Bailey, A., Dugan, A. (2023).	Dual Center Retrospective Cohort Study	– This study composed of a retrospective cohort chart review for patients presenting to two Kentucky Emergency Departments between Jan 1, 2015 to March 1, 2020 who received an IV of either Diltiazem or IV Metoprolol for management of their A-fib with RVR   – There was a total of 305 patients   – 206 patients were in the IV Diltiazem group   – 99 patients were in the IV Metoprolol group	– The primary outcome was the time it took to successfully control the patients heart rate (which was a HR of under 110 BPM) after medication administration   – Secondary outcomes included of any adverse effects that included hypotension (SBP under 90mmHg), bradycardia (HR under 60 BPM), and what the length of hospital stay was   – Statistical analysis was preformed using the R programming language, version 4.1.1	– The primary outcome of the time to reduce a patient’s heart rate successfully under 110 BPM was not statistically different between either medication   – There were no statistical differences in all the secondary outcomes between either medication used which included any adverse effects that led to hypotension, bradycardia, or an extended length of stay at the hospital	– The number of patients in this study was much smaller than in any other studies discussed   – There was a vast difference in the treatment arms with respect to how many patients were in each arm (effectively it was 2-1 favoring diltiazem)
McGrath, P., Kersten, B., Chilbert, M., Rusch, C., Nadler, M. (2021)	Retrospective Cohort Study	– Between Jan 1, 2015 and June 30, 2019 349 patients were treated in a Buffalo emergency department for their A-fib with RVR   – 183 patients were given IV Diltiazem   – 166 patients were given IV Metoprolol	– The primary outcome was achieving rate control at the two-hour mark after the last IV bolus of the drug was given   – The secondary outcomes included achievement of rate control at one hour; comparisons of: heart rate at half an hour, 1 and 2 hr; heart rate as a percent change at half an hour, 1 and 2 hr; if the patient required hospital admission or ICU admission; hospital length of stay; ICU length of stay; and time to rate control   – Statistical analysis was performed using SAS, version 9.4 (SAS Institute Inc., Cary, NC)	– There was no statistical difference between both treatment arms in regards to the primary outcome of achieving rate control at the two- hour mark   – There were no statistical differences that were associated with either drug in regards to hospital admissions, ICU admissions, hospital length of stay, ICU length of stay   – Two patients in the metoprolol group and seven patients in the diltiazem group experienced bradycardia (HR <60BPM)   – 39.3% of the diltiazem group experienced hypotension versus only 23.5% of the metoprolol group	– The number of participants in this study was extremely limited   – The timed intervals were not always on time (half an hour meant any time between 16-45 min, and so on)
Nicholson, J., Czosnowski, Q., Flack, T., Pang, P., Billups, K. (2020)	Single Center Retrospective Cohort Study	– 108 patients were treated for their A-fib with RVR at an Indiana emergency room between July 1, 2008 and July 1, 2018   – 63 patients were given IV Diltiazem   – 45 patients were given IV Metoprolol	– The primary outcome was the reduction of the systolic blood pressure from the first IV dose of diltiazem or metoprolol to 30 min after the last IV dose   – Secondary outcomes included any instances of hypotension, and if rate control was achieved   – Statistical analysis was performed using Minitab 18.1 statistical software 2018 (State College, PA)	– The primary outcome of reducing the systolic blood pressure was not statistically different between either treatment arm   – There was also no difference between any instances of hypotension between either drug   – More patients achieved rate control faster with IV diltiazem (56% of the cohort) versus with IV metoprolol (36% of the cohort)	– This study had the smallest patient population among all the studies we have had   – Continuous vital sign monitoring and repeat EKGs were not always available as the patient progressed through treatment   – The treatment arms were not as balanced as with other studies

Conclusion(s):

Article 1 concluded by saying patients who were treated with IV diltiazem had a higher efficacy of the drug working, shorter onset time, and decreased heart rates than those who were treated with IV metoprolol. There was no difference in the instances of hypotension or adverse events with either drug.

Article 2 concluded by saying the use of IV diltiazem in patients with A-fib with RVR saw a faster achievement of rate control than those who used IV metoprolol. There were similar instances of hypotension and bradycardia between both drugs.

Article 3 concluded by saying there were no significant differences in the time to achieve rate control following the administration of either IV diltiazem or IV metoprolol. There were also no significant differences in secondary outcomes including hospital length of stay, hypotension, or bradycardia between either treatment group.

Article 4 concluded by saying there were no differences in achieving rate control between either treatment arm after two hours after the last bolus was delivered. IV diltiazem did achieve a significant greater reduction in heart rate at the half hour mark, but both treatments were not statistically different at the two-hour mark. More patients in the IV diltiazem group experienced both hypotension and bradycardia than in the IV metoprolol group

Article 5 concluded by saying the instances of hypotension and reduction of systolic blood pressure were similar in both treatment arms, although more patients who were administered IV diltiazem achieved rate control faster than those who were given IV metoprolol.

My overall conclusion based off these 5 studies is that using IV diltiazem or IV metoprolol are both efficacious in achieving rate control for patients with atrial fibrillation with rapid ventricular rate. Although, I would say using IV diltiazem did show better instances of achieving rate control faster than IV metoprolol.

Clinical Bottom Line:

I will weigh my studies in the following order: Article 2, Article 1, Article 4, Article 3 and lastly Article 5.

I weighed article 2 the highest of all my articles. This article was my only systematic review and meta-analysis and it had close to 2,000 participants (all who stemmed from the emergency department). The article mentioned that patients treated with intravenous diltiazem had significantly greater achievement of rate control target (odds ratio of 1.92) compared to patients treated with intravenous metoprolol (odds ratio of 1.26) meaning patients who were treated with IV diltiazem had almost two times significantly greater achievements hitting their rate control target than patients who were treated with IV metoprolol. Additionally with this study being done in 2022, I was very pleased with how recent the article was. The primary outcome was exactly what my question was asking as well as the secondary outcomes referencing hypotension and bradycardia.

I weighed article 1 the next highest because it was a meta-analysis with over 1,200 participants. IV diltiazem was shown to have a higher efficacy in achieving rate control faster during the 30 minute and 60-minute time frames, shorter average onset of time to action, and a faster decrease in heart rates during the 5, 10, 15, 30, 60 and 90-minute time frames versus IV metoprolol.

Next for me is article 4. The primary outcomes of this study showed there were no statistical differences between achieving rate control by the two-hour mark, as well as no differences in hospital admissions, ICU admissions, hospital length of stay, or ICU length of stay. The interesting part of the article came almost at the end that showed participants who were treated with IV diltiazem had more incidences of hypotension (39.3% of the cohort) and bradycardia (3.83%), than those in the IV metoprolol group (where only 23.5% experienced hypotension and 1.2% experienced bradycardia).

Next was article 3 for me. This article had over 300 participants, and looked at efficacy of rate control, and for any incidences of hypotension and bradycardia, but the treatment arms were very disjointed. There was a 2-1 ratio of patients who got IV diltiazem versus patients who got IV metoprolol. Ultimately, there were no significant differences found in the time to adequate rate control between using IV diltiazem or IV metoprolol.

Lastly for me is article 5. This article had the least number of patients, at a little over 100 participants. The primary outcome also looked at reduction of systolic blood pressure, which was not what I was initially looking for with my clinical question, which was achieving rate control. Ultimately, hypotension was not significantly found to be a factor in either treatment arm (14% of the IV diltiazem cohort vs. 16% of the IV metoprolol cohort). Conversely, more patients who received IV diltiazem obtained rate control faster than the patients who received IV metoprolol (56% of the IV diltiazem cohort vs. 36% of the IV metoprolol cohort).

Clinical significance (not just statistical significance)

IV diltiazem showed better rate control over IV metoprolol in the systematic reviews/meta-analysis, but showed no statistical differences in the single and dual emergency room studies in the different cities in the United States. I would say using either diltiazem or metoprolol will both get the patient to achieve rate control without any adverse events happening.

Any other considerations important in weighing this evidence to guide practice 

Many of my articles mentioned that further investigation was needed into whether IV diltiazem or IV metoprolol was more efficacious in achieving rate control quicker with higher-blinded randomized control studies with more participants. One of the articles mentioned that IV diltiazem did show more incidences of hypotension and bradycardia, so if a clinician was worried about their patient getting to dangerous cardiac levels, they should use IV metoprolol over IV diltiazem to overcome that precaution.