|Author, date and country||Patient group||Study type (level of evidence)||Outcomes||Key results||Study Weaknesses|
|Schreck et al,|
|30 consecutive patients presenting to an ED with acute onset AF or atrial flutter randomised to receive either: 9 patients allocated to IV digoxin 0.25 mg and again 30 min later; 11 patients allocated to IV diltiazem at an initial dose of 0.25 mg/kg, followed by 0.35 mg/kg at 15 min followed by an infusion of 10 mg/h to a maximum of 20 mg/h to keep VR ,100 bpm; 10 patients allocated to both IV diltiazem and digoxin. Excluded if BP,100 mm Hg systolic, drug allergy, acute MI or heart failure (NYHA Class 3 or 4), IV beta-blocker in preceding hour, WPW, SSS, cardiogenic shock, current treatment with calcium channel blockers other than diltiazem.||Unblinded randomised controlled trial||VR control measured over 3 h as defined as a HR ,100.||Rate control achieved within 15 min for IV diltiazem group and at 30 min for IV dlitiazem with digoxin group but not achieved at any time with IV digoxin alone.|
Reduction in HR in digoxin group reached significance at 3 h (p=0.0099).
No additional benefit for HR control with the addition of digoxin to diltiazem
|Unblinded but adequately powered study, only lasting 3 h. Dose of digoxin given as two boluses of 0.25 mg. Exclusions include those patients with acute MI and pulmonary congestion and those with severe heart failure. Not adequately powered to study complications|
|Blood Pressure||Blood pressures lower with IV diltiazem|
|Innes et al, |
|Convenience sample of 41/451 ED patients age 18–75, presenting in AF of ,48 h duration.|
22 patients allocated to receive verapamil 5 mg IV, repeated at 20, 60 and 120 min if HR .100. 19 patients allocated to digoxin 0.5 mg IV and 0.25 mg at 60 and 120 min if HR .100. Placebo was given to ensure patients and clinicians were blinded.
Exclusion criteria of HR ,100 or 200, allergy to study drugs, BP ,90 mm Hg with clinical evidence of hypoperfusion, heart block, SSS or prolonged QRS interval.
|Randomised controlled trial||Number of patients with HR ,100.||5/22 patients receiving verapamil converted to sinus rhythm prior to rate control.|
10/19 patients receiving digoxin converted to sinur rhythm prior to achieving rate control.
Results difficult to extract from graph accurately, however at 20 min, average HR in verapamil group about 100 and digoxin about 130. At 40 min these results are 100 and 120, respectively. At 180 min the results are unchanged.
|Small study. Study designed to compare the speed and success of cardioversion using first verapamil or digoxin (to control the rate), then quinidine (to cardiovert). Results are hard to extract.|
|Tisdale et al,|
|40 patients with acute AF within 7 days of CABG.|
20 patients assigned to diltiazem 20 mg IV followed by 25 mg 15 min later. An infusion of 10 mg/h was started and increased 1 h later to 15 mg/h if ,20% decrease in ventricular rate. 20 patients assigned to digoxin 0.5 mg IV followed by 0.25 mg and 0.25 mg at 3 and 6 h. Placebo administered to enable blinding of doctors and patient.
Exclusions included BP ,100 mm Hg, heart failure, renal failure, mechanical ventilation, hypokalaemia, hypomagnesaemia, heart block, WPW or administration of digoxin or calcium antagonist.
|Randomised controlled trial||Ventricular rate control (.20% decrease) Time to ventricular rate control||At 2 h, 15/20 with diltiazem and 7/20 with digoxin, achieved rate control (p=0.03).At 6 h, 17/20 with diltiazem and 9/20 with digoxin achieved rate control (p=0.02). At 12 h, 17/20 with diltiazem and 13/20 with digoxin achieved rate control (p=0.27). At 24 h, 19/20 with diltiazem and 17/20 with digoxin achieved rate control (p=0.61)||All patients had undergone CABG in previous 7 days.|
Only 40/101 potential patients included because of wide exclusion criteria.
|Adverse events||3/20 with diltiazem developed hypotension. 1/20 with digoxin had sinus pauses on ECG.|
|Tan et al,|
|54 patients presenting with acute AF or atrial flutter.|
34 patients were randomised to IV diltiazem or 20 patients were randomised to IV cediland.
|Single blind randomised trial.||Mean decrease in heart rate.||IV diltiazem group 34% and IV cediland group 23% reduction in HR from baseline.||Small study|
Details were difficult to extract as only the abstract available in English.
|Mean response time to bolus.||IV diltiazem 7 min and IV cediland 33 min.|
|Side effects of drugs including effects on LV function, blood pressure and arrhythmias||No worsening of LVF in any patient.|
In the IV diltiazem group, 2/34 had asymptomatic hypotension and 1/34 had a ventricular pause.
|Siu et al,|
|150 ED patients with acute symptomatic AF ,48 h duration with VR .120 bpm. 50 patients allocated to IV diltiazem 0.25 mg/kg over 2 min followed by
0.35 mg/kg if initial bolus failed, followed by infusion of 10 mg/h for 24 h. 50 patients allocated to digoxin 0.5 mg IV followed by 0.25 mg every
8 h (1.25 mg over 24 h). 50 patients allocated to amiodarone 300 mg over 1 h followed by 10 mg/kg over the next 24 h.|
Excluded if BP 90 mm Hg, congestive heart failure, recent ACS, VR .200 bpm, WPW, CVA or PE within 6 months, antiarrhythmic use, allergy to study drugs or other major medical condition.
|Open-label randomised controlled trial.||Time to control of VR ,90.||Median time to VR control significantly shorter for diltiazem group compared with digoxin or amiodarone (3 h vs 6 h vs 7 h, respectively p,0.0001).||Initial digoxin dose low as was maintenance dose of amiodarone. Open-label study, therefore potential bias in assessment of AF symptoms. Adverse effects only defined as HR ,50 bpm for .30 min or BP,60 mm Hg systolic.|
|Sustained control of VR defined as VR ,90 bpm for .4 h at 24 h.||Patients in diltiazem group significantly more likely to achieve control of VR within 24 h than those in the digoxin or amiodarone group (90% vs 74% vs 74%, respectively, p=0.047).|
|Improvement of symptoms.||AF symptom score significantly lower in diltiazem group at 24 h compared with digoxin (p=0.047) and amiodarone (p=0.01).|
|Length of stay in hospital.||Length of stay significantly less in diltiazem group compared with digoxin or amiodarone group (3.9 days vs 4.7 days vs 4.7 days respectively, p=0.023).|
|Adverse events.||One case of phlebitis in amiodarone group, no other adverse effects.|