Cardiovascular Journal of Africa: Vol 32 No 6 (NOVEMBER/DECEMBER 2021)

CARDIOVASCULAR JOURNAL OF AFRICA • Volume 32, No 6, November/December 2021 AFRICA 333 therapy. At six months’ follow up, both groups had similar rates of freedom from AF (71% in the off-amiodarone group vs 75% in the on-amiodarone group, p = 0.702). At 32 ± 8 months, a higher success rate without AAD was demonstrated for patients in the off-amiodarone group (66 vs 34%, p < 0.002). The study by Zhang et al . suggests that a second ablation procedure renders better results than AAD use in cases of persistent AF. 100 Safety profile of amiodarone Amiodarone has a wide spectrum of adverse effects, with a prevalence of 15% in the first year of administration, which may increase up to 50% in the case of prolonged administration. 16 Potential adverse effects include toxicity involving the lungs, heart, thyroid gland, liver, skin, eyes and nerves (Table 6). While the majority of adverse effects are reversible after amiodarone dose reduction or discontinuation, fatal complications have also been reported. These include pulmonary fibrosis, liver cirrhosis or bradycardia that may lead to cardiac arrest. At risk for pulmonary fibrosis are patients with an underlying lung disease or with a dosage of amiodarone greater than 400 mg/day. Therefore amiodarone should not be used in patients with significant pulmonary disease, significant liver disease or with symptomatic conduction system disease. Follow up of patients on amiodarone treatment is mandatory to detect and limit its adverse effects. Routine screening is recommended every six months, with lung function assessment including chest radiography, liver and thyroid function tests, ECG, and an annual eye examination. 101 Moreover, amiodarone acts as an inhibitor of several cytochrome P450 pathways, such as CYP3A4 or CYP2C9, therefore resulting in alterations in plasma concentrations of many common drugs. The main amiodarone drug interactions are listed in Table 7. 16,112–114 An important interaction is potentiation of the warfarin anticoagulant effect, with the recommendation to monitor prothrombin times closely and to reduce the dose of anticoagulant if needed. 115,116 Amiodarone can also increase digoxin levels, therefore dose reduction and close monitoring of serum digoxin levels is recommended. 114 To avoid adverse drug– drug interactions, patients under treatment with amiodarone should therefore consult their cardiologist whenever a new drug is prescribed. The most important studies on the side effects of amiodarone versus other AADs are listed in Table 8. We evaluated the withdrawal rate due to AAD side effects as well as pro-arrythmic events. Following the comparison studies between amiodarone and class I or III anti-arrhythmics, we obtained the following results: amiodarone had a lower withdrawal rate than class I drugs combined and no statistically significant difference when compared to dronaderone or sotalol. As for pro-arrhythmia, Table 6. Adverse effects of amiodarone Adverse effect Incidence (%) Reference Pulmonary toxicity 2 102 Bradycardia 5 103 Torsade de pointes < 1 104 Hyperthyroidism 3 105 Hypothyroidism 4–22 8 Hepatitis and cirrhosis < 3 102, 106 Nausea, anorexia, constipation 30 107 Photosensitivity 25–75 105 Grey-blue discoloration < 10 105 Corneal microdepositions > 90 101 Optic neuropathy < 1 108,109 Neurologic: ataxia, tremor, 3–30 110, 111 peripheral neuropathy Table 7. Main interactions of amiodarone with other drugs Amiodarone plus Interactions Coumadin derivates Potentiates the anticoagulant effect and increases phrotrombin time Digoxin Increases digoxin level Beta-blockers, calcium channel blockers May cause bradycardia, sinus arrest or AV block Class IA anti-arrhythmics drugs, macrolide antibiotics, tricyclic antidepressants May prolong QTc Hypokalaemia-causing drugs (diuretics) May increase the risk of Torsades de points DOACs May increase its bioavailability, but does not affect efficacy or safety outcomes Statins (lovastatin, simvastatin) May increase the risk of rhabdombyolisis or myopathy Flecainide Increases flecainide levels Table 8. The most important trials that evaluated amiodarone vs other AAD for withdrawals due to side effects and for pro-arrhythmic events Trial AADs compared Number Mean age (years) Greater withdrawals due to side effects,RR (95% CI) Greater pro-arrhythmia, RR (95% CI) DYONISOS 2010 50 Amiodarone vs dronaderone 504 64 Amiodarone 1.37 (0.9–2.09) Amiodarone 1.95 (0.36–10.57) Pitagora 2008 51 Amiodarone vs flecainide/propafenone 176 72 Amiodarone 1.11 (0.23–5.4) Not studied Pitagora 2008 51 Amiodarone vs sotalol 176 72 Amiodarone 5.86 (0.34–100.89) Not studied Vijayalaskshmi 2006 52 Amiodarone vs sotalol 78 64 Sotalol 0.38 (0.04–3.14) Not studied Niu 2006 53 Amiodarone vs sotalol 102 56 Sotalol 0.71 (0.24–2.1) Not studied Kochiadakis 2004 55 Amiodarone vs propafenone 254 63 Amiodarone 8.74 (2.09–36.4) Similar 1.03 (0.15–7.10) AFFIRM sub-study 2003 58 Amiodarone vs class I drug 410 69 Class I drug 0.33 (–0.21–0.53) Class I drug 0.20 (0.08–0.51) AFFIRM sub-study 2003 58 Amiodarone vs sotalol 410 69 Sotalol 0.83 (0.47–1.47) Sotalol 0.49 (0.17–1.42) Kochiadakis 2000 59 Amiodarone vs sotalol 186 63 Amiodarone 3.44 (1.01–11.75) Similar 0.94 (0.14–6.46) Villani 1992 62 Amiodarone vs disopyramide 76 65 Disopyramide 0.35 (0.1–1.18) Not studied Vitolo 1981 65 Amiodarone vs quinidine 54 53 Similar 0.93 (0.06–14.09) Similar 0.93 (0.06–14.09) AAD, anti-arrhythmic drug.