Introduction
Methods
Discussion
Current Antiarrhythmic Therapy
Classification of Antiarrhythmic Agents
Drug [reference] | V-W class | Dosage (oral) | Metabolism | Adverse effects | Drug–drug interactions |
---|---|---|---|---|---|
Quinidine [21] | IA | 324–648 mg q8h (gluconate) 300–600 mg q6h (sulfate) | Hepatic (CYP3A4) and renal | Diarrhea, stomach cramps, tinnitus, fever, rash, thrombocytopenia, hemolytic anemia, QT prolongation, torsades | ↓ digoxin dose by 50%; ↓ warfarin and beta-blocker dose; amiodarone, cimetidine and verapamil may ↑ quinidine levels |
Disopyramide [21] | IA | 150–300 mg q6h (150 mg q12–24h in moderate–severe CKD) | Primarily renal | Urinary retention, blurred vision, constipation, dry mouth, QT prolongation, torsades | Phenytoin may ↓ disopyramide levels; use caution with co-administration of other QT prolonging medications |
Mexiletine [21] | IB | 150–300 mg q8h | Hepatic (CYP2D6) | Nausea, stomach cramps, tremor, blurred vision, ataxia, confusion | Cimetidine and quinidine may ↑ mexiletine levels |
Flecainide [21] | IC | 50–200 mg q12h (50–200 mg q24h in significant CKD) | Hepatic (CYP2D6) and renal | Tremor, blurred vision, headache, ataxia, PR and QRS prolongation, proarrhythmia | Amiodarone, cimetidine, propranolol and quinidine may ↑ flecainide levels |
Propafenone [21] | IC | 150–300 mg q8h | Hepatic (CYP2D6, 3A4, 1A2) | Constipation, dizziness, headache, metallic taste, bronchospasm, bradycardia, PR and QRS prolongation, proarrhythmia | ↓ digoxin dose by 25–50%; cimetidine and quinidine may ↑ propafenone levels |
Amiodarone [22] | III | Loading dose 400 mg q6–12h for 10 g Maintenance dose 200–600 mg/day | Hepatic (CYP3A4) | Pulmonary toxicity, hypo/hyperthyroidism, hepatic toxicity, neuropathy, corneal deposits, bradycardia, prolongation of PR, QRS, QT | ↓ digoxin and warfarin dose by 25–50% |
Sotalol [22] | III | Start 80 mg q12h (80 mg q24h if moderate CKD) Maintenance dose 80–160 mg q12h (40–80 mg q12h in CKD). Avoid in severe CKD | Renal | Bradycardia, fatigue, bronchospasm, heart failure, QT prolongation, torsades | Use caution with co-administration of other QT prolonging medications |
III | 500 µg q12h if CrCl >60; 250 µg q12h if CrCl 40–60; 125 µg q12h if CrCl 20–39. Avoid in severe CKD | Renal and hepatic (CYP3A4) | Headache, chest pain, dizziness, respiratory tract infection, dyspnea, nausea, QT prolongation, torsades | Do not administer dofetilide with cimetidine, ketoconazole, prochlorperazine, megestrol, verapamil, trimethoprim or hydrochlorothiazide | |
III | 400 mg q12h | Hepatic (CYP3A4) | Diarrhea, nausea, stomach cramps, QT prolongation, bradycardia, heart failure, hepatic toxicity | Verapamil and diltiazem may ↑ dronedarone levels; dronedarone may ↑ digoxin, beta-blocker and simvastatin levels | |
IB | 500–1,000 mg q12h | Hepatic (CYP3A4) | Dizziness, headache, nausea, QT prolongation | Ranolazine may ↑ digoxin and simvastatin levels; diltiazem and verapamil may ↑ ranolazine levels |
Study [reference] | Population | N | Agent(s) studied | Follow-up | Primary endpoint | Results |
---|---|---|---|---|---|---|
CIBIS II [30] | Heart failure with NYHA Class 3 or 4 symptoms, ejection fraction ≤35% | 2,647 | Bisoprolol vs. placebo | Mean of 1.3 years | All-cause mortality | Mortality was lower with bisoprolol compared to placebo (11.8% vs. 17.3%; hazard ratio 0.66, P < 0.0001). Sudden death was lower with bisoprolol compared to placebo (3.6% vs. 6.3%; hazard ratio 0.56, P = 0.0011) |
COMMIT [31] | Acute MI patients within 24 h of suspected onset | 45,852 | Metoprolol (IV plus oral) vs. placebo | 28 days | 1. Death, reinfarction, or cardiac arrest 2. Death from any cause | No significant difference in either primary outcome. Fewer patients had ventricular fibrillation with metoprolol vs. placebo (2.5% vs. 3.0%; odds ratio 0.83, P = 0.001) but more developed cardiogenic shock (5.0% vs. 3.9%; odds ratio 1.30, P < 0.00001) |
OPTIC [19] | Secondary prevention ICD recipients | 412 | Amiodarone + beta-blocker vs. sotalol vs. beta-blocker | 1 year | ICD shock for any reason | Fewer shocks with amiodarone + beta-blocker (10.3%) compared to sotalol (24.3%) or beta-blocker alone (38.5%) |
Pacifico et al. [32] | Secondary prevention ICD recipients | 302 |
d,l-sotalol vs. placebo | 1 year | Death or ICD shock from any cause | Lower risk of death or ICD shock with sotalol over placebo (reduction in risk, 48%, P < 0.001). Sotalol also reduced the mean frequency of shocks due to any cause (1.43 vs. 3.89 shocks per year, P = 0.008) |
SWORD [33] | Previous MI, ejection fraction ≤40% | 3,121 |
d-Sotalol vs. placebo | Mean of 148 days | All-cause mortality | Higher risk of death with d-sotalol over placebo (5.0% vs. 3.1%; relative risk 1.65, P = 0.006). Arrhythmic deaths accounted for the increased mortality |
EMIAT/CAMIAT pooled analysis [34] | Survivors of acute MI with either ejection fraction ≤ 40% (EMIAT), or with frequent ventricular ectopy (CAMIAT) | 2,687 | Beta-blockers + amiodarone, beta-blockers alone, amiodarone alone vs. placebo | 2 years | All-cause mortality, cardiac death, arrhythmic cardiac death, nonarrhythmic cardiac death, arrhythmic death, or resuscitated cardiac arrest | Event rates were significantly lower for patients receiving beta-blockers + amiodarone compared to beta-blockers alone, amiodarone alone, or placebo |
CAST [35] | Survivors of acute MI with frequent ventricular ectopy | 1,498 | Encainide or flecainide vs. placebo | Mean of 10 months | All-cause mortality | Increased mortality with encainide or flecainide compared to placebo, including both arrhythmic death (P = 0.0004), and nonarrhythmic cardiac death (P = 0.01) |
SHIELD [36] | ICD recipients with history of VT/VF | 633 | Aimilide vs. placebo | 1 year | 1. All-cause shocks plus symptomatic tachyarrhythmias terminated by antitachycardia pacing 2. All-cause shocks | All-cause shocks plus symptomatic ventricular tachycardia terminated by antitachycardia pacing were significantly reduced by azimilide (hazard ratio 0.43, P = 0.0006 on 75 mg dose; hazard ratio 0.53, P = 0.0053 on 125 mg dose). The reductions in all-cause shocks on azimilide were not statistically significant |
ALPHEE [37] | ICD recipients with history of VT/VF and ejection fraction ≤40% | 486 | Celivarone vs. placebo | Median of 9 months | ICD therapy for VT/VF or sudden death | No significant difference in the primary outcome with celivarone vs. placebo |