By Arzo Hamidi, PharmD, BCCCP
Clinical Pharmacy Specialist, Adult Critical Care, Rush University Medical Center, Chicago
SYNOPSIS: In patients with atrial fibrillation and heart failure, intravenous diltiazem results in greater heart rate reduction than metoprolol with a similar safety profile, but further research is needed in this patient population.
SOURCE: Compagner CT, Wysocki CR, Reich EK, et al. Intravenous metoprolol versus diltiazem for atrial fibrillation with concomitant heart failure. Am J Emerg Med 2022;62:49-54.
This was a retrospective study of adult patients who presented to the emergency departments (EDs) across a health system with atrial fibrillation with rapid ventricular response (RVR), defined as heart rate (HR) ≥ 120 bpm. The patients had documented heart failure (HF) by echocardiogram within the last 12 months or within 24 hours of admission. Patients were excluded if they were in an acute HF exacerbation upon admission, or if they received antiarrhythmic or other rate-controlling agents prior to or within the first 30 minutes after intravenous (IV) metoprolol or IV diltiazem.
The primary outcome was HR < 110 bpm within 30 minutes after metoprolol or diltiazem administration. The secondary outcomes were HR < 110 bpm within 60 minutes and HR < 110 bpm at ED discharge or transfer. Safety outcomes included bradycardia (HR < 60 bpm) within six hours, hypotension (systolic blood pressure ≤ 90 mmHg) within six hours, shortness of breath, vasopressor use within 24 hours, change in ejection fraction (EF) on echocardiogram, and acute kidney injury.
This study included 193 patients, with 59 receiving metoprolol and 134 receiving diltiazem. The average patient was 73 years old, female, and white. More than 60% of patients had heart failure with preserved ejection fraction (HFpEF) and 30% had heart failure with reduced ejection fraction (HFrEF). In patients with HFrEF, the average EF was 48%. The primary outcome of HR < 110 bpm at 30 minutes was not significantly different between the groups (55% in the diltiazem group vs. 41% in the metoprolol group; P = 0.063). However, the absolute heart rate was reduced by 33 bpm with diltiazem compared to 20 bpm with metoprolol (P < 0.001). At 60 minutes, the percentage of those with HR < 110 bpm was not significantly different between the groups (58% in the diltiazem group vs. 46% in the metoprolol group; P = 0.133). At the time of ED discharge/transfer, more patients receiving diltiazem had heart rates < 110 bpm compared to those receiving metoprolol (72% vs. 56%, respectively; P = 0.033). There were no significant differences in any of the safety outcomes.
COMMENTARY
The use of non-dihydropyridine calcium channel blockers is not recommended in patients with HF because of potential negative inotropy. This study included patients with reduced, mildly reduced, or preserved EF. This study shows that compared to metoprolol, diltiazem was effective at HR control, with faster time to HR goal and greater absolute reductions but with no differences in safety. In reviewing the patients with preserved EF, the diltiazem group had more patients with HR < 110 bpm and a greater HR reduction between groups at 30 minutes. Within current guideline recommendations, it is unclear if diltiazem is more effective in certain subcategories of HF.
It is important to consider that the overall baseline HR was lower in the metoprolol vs. the diltiazem group (135 bpm vs. 142 bpm, respectively; P = 0.004). It also is noteworthy that 83% of patients receiving IV metoprolol and 88% receiving IV diltiazem were taking beta-blockers prior to admission. It is unclear if the specific home medication drives providers to use beta-blockade in the hospital due to known nonadherence or to optimize home dosages, or, alternatively, if it drives providers to use an agent in an alternative class because of inefficacy. In either case, the lower baseline HR should be noted when evaluating the absolute reduction in HR between groups.
The crossover rate between groups was low, but 54% of patients receiving IV push diltiazem were started on diltiazem via continuous infusion and 17% of those receiving IV push metoprolol were also started on diltiazem via continuous infusion. More patients in the metoprolol group also received concomitant amiodarone than in the diltiazem group, but a similar number of patients received digoxin in both groups. The differences in these alternative agents also may have affected outcomes.
The most common doses used were metoprolol 5 mg and diltiazem 10 mg. The average weight of patients receiving diltiazem was 90 kg; considering the weight-based dose is 0.25 mg/kg, providers should have used higher doses. The average dose of diltiazem was 13.8 mg, with only 18% of patients receiving more than one dose. Based on this study, it is unclear if lower weight-based doses of diltiazem in this patient population are as effective as normal doses or if higher doses would have resulted in a greater efficacy at the cost of a higher number of safety events.
With regard to safety in patients with HFpEF, there was more hypotension within six hours of diltiazem administration compared to metoprolol (28% vs. 7%, respectively; P = 0.005). Conversely, in patients with HFrEF, there was more hypotension within six hours of metoprolol administration compared to diltiazem, although this was not significantly different (31% vs. 17%, respectively; P = 0.238). This should spark further study of IV metoprolol vs. diltiazem among patients with varying EF for the treatment of atrial fibrillation with RVR with a goal of specifying dosing in these patient populations.
