Comparing Two Heart Medicines for Fast, Irregular Heartbeat (Atrial Fibrillation)

Verapamil Versus Metoprolol for Rate Control in Hemodynamically Stable Atrial Fibrillation With Rapid Ventricular Response

The goal of this clinical trial is to learn whether intravenous verapamil or intravenous metoprolol controls heart rate more effectively in adult patients who arrive at the emergency department with atrial fibrillation and a fast heart rate (rapid ventricular response), but who are otherwise medically stable. Atrial fibrillation with a rapid heart rate is a common emergency, and doctors currently choose between these two standard medicines based on personal preference rather than strong local evidence, since there is limited research on this comparison in Pakistani patients.

The main questions this study aims to answer are:

Does a higher proportion of patients reach a target heart rate of less than 110 beats per minute within 30 minutes with verapamil compared to metoprolol? Which medicine controls the heart rate faster, on average? Are there differences in side effects (such as low blood pressure, slow heart rate, or breathing problems) between the two medicines? Researchers will compare a group of patients receiving verapamil to a group receiving metoprolol to see if one medicine controls the heart rate faster and more safely than the other.

Participants will:

1. Receive either verapamil or metoprolol through an IV, with the dose given according to standard protocols
2. Have their heart rate, blood pressure, and oxygen levels monitored continuously for 30 minutes after the medicine is given
3. Be observed for any side effects during this monitoring period Both medicines used in this study are already standard, guideline-recommended treatments for this condition, so participation will not change or delay the medical care patients would normally receive.

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia encountered in clinical practice, and rapid ventricular response (RVR), defined as a ventricular rate greater than 110 beats per minute, is a frequent reason for emergency department presentation. In hemodynamically stable patients, pharmacological rate control-rather than immediate cardioversion-is the primary initial management strategy, aiming to restore an acceptable ventricular rate, relieve symptoms, and improve cardiac output.

Intravenous non-dihydropyridine calcium channel blockers (such as verapamil) and cardio-selective beta-blockers (such as metoprolol) are both recommended as first-line agents for acute rate control by major international guidelines, including those of the American College of Cardiology (ACC) and the European Society of Cardiology (ESC). However, existing trials and observational studies comparing these two drug classes have produced mixed findings: some studies suggest verapamil achieves faster rate control due to more direct atrioventricular (AV) nodal inhibition, while others report comparable efficacy, with metoprolol offering a safer profile in patients with reactive airway disease or mild-to-moderate left ventricular dysfunction. A prior meta-analysis suggested verapamil may reach target heart rate faster than metoprolol, though both drugs demonstrated acceptable safety in hemodynamically stable patients.

There is limited data from South Asian, and specifically Pakistani, emergency medicine settings, where the epidemiological profile of AF differs (with a higher burden of uncontrolled hypertension, ischemic heart disease, and valvular disease as underlying substrates) and where rate-control drug selection is often based on physician preference rather than locally generated evidence.

This study is a randomized controlled trial conducted in the Emergency Department of Pakistan Ordnance Factories (POF) Hospital, Wah Cantt. Eligible adult patients (≥18 years) with confirmed AF-RVR (ventricular rate ≥110 bpm on 12-lead ECG) who are hemodynamically stable (systolic BP ≥90 mmHg, no altered consciousness, no cardiogenic shock, no chest pain, no acute pulmonary edema) will be randomized in a 1:1 ratio using a computer-generated sequence to one of two treatment arms:

1. Group A (Verapamil): Initial IV dose of 5 mg over 2 minutes; if target heart rate is not achieved within 15 minutes, a further 5 mg IV dose may be given, to a cumulative maximum of 10 mg.
2. Group B (Metoprolol): Initial IV dose of metoprolol tartrate 5 mg over 2 minutes; if target heart rate is not achieved within 5 minutes, up to two additional 5 mg IV doses may be given at 5-minute intervals, to a cumulative maximum of 15 mg.

Both groups will undergo continuous cardiac monitoring, pulse oximetry, and non-invasive blood pressure measurement throughout the observation period, with vital signs recorded at baseline and at 5, 10, 15, 20, and 30 minutes post-drug administration. A trained research officer, blinded to study analysis, will document adverse events, need for rescue medication, and clinical outcomes using a structured proforma.

The primary outcome is the proportion of patients in each group achieving a ventricular rate below 110 bpm within 30 minutes of study drug administration. Secondary outcomes include the mean time to achieve target heart rate and the incidence and nature of adverse drug events (including symptomatic hypotension, bradycardia, high-degree AV block, and bronchospasm) in each group.

Sample size was calculated using a two-proportion comparison based on previously reported rate-control success rates of 78% for verapamil and 58% for metoprolol (95% confidence interval, 80% power), yielding 54 patients per group, adjusted to 60 per group (120 total) to account for anticipated dropout. Data will be analyzed using SPSS version 29.0, with independent samples t-test or Mann-Whitney U test for continuous variables, chi-square or Fisher's exact test for categorical outcomes, and Kaplan-Meier survival analysis with log-rank test for time-to-rate-control comparisons. A p-value <0.05 will be considered statistically significant.

The study will be conducted in accordance with the Declaration of Helsinki (2013 revision) and Good Clinical Practice (GCP) guidelines, with prior approval from the Institutional Review Board / Ethics Committee of POF Hospital, Wah Cantt, and written informed consent obtained from all participants in English and Urdu.

Inclusion Criteria:

• Adult patients aged 18 years and above presenting to the Emergency Department
• Confirmed diagnosis of atrial fibrillation with rapid ventricular response (heart rate ≥110 bpm) on 12-lead ECG
• Hemodynamically stable at the time of enrollment (systolic blood pressure ≥90 mmHg, no shock, no acute pulmonary edema)
• Willingness to provide written informed consent

Exclusion Criteria:

• Hemodynamic instability, cardiogenic shock, or acute decompensated heart failure
• Known pre-excitation syndrome (e.g., Wolff-Parkinson-White syndrome) on baseline ECG
• Severe left ventricular systolic dysfunction (ejection fraction less than 30%) as determined by echocardiography
• Known hypersensitivity or contraindication to verapamil or metoprolol
• Patients already taking rate control agents (beta-blockers, calcium channel blockers, or digoxin) in the last 24 hours
• Major bradycardia (heart rate less than 50 bpm) or AV block (second or third degree) on baseline ECG
• Active bronchospasm or severe obstruction of pulmonary disease
• Severe hepatic impairment (Child-Pugh Class C) or acute renal failure (eGFR <15 mL/min/1.73 m²)
• Pregnancy or breastfeeding
• Inability to give informed consent