Drug Therapy for the Management of Atrial Fibrillation: An Update

Andrew RJ Mitchell

Disclosures

Br J Cardiol. 2003;10(5) 

In This Article

Facilitation of Cardioversion and Prevention of Persistent Atrial Fibrillation Recurrence

Electrical cardioversion of persistent AF is successful in 80–90% of patients and this can be increased further by pre-treatment with sotalol, ibutilide or amiodarone.[31,32,33] These drugs work by reducing the atrial defibrillation threshold and by preventing some of the immediate recurrences of AF.

The relapse rate of AF after cardioversion is extremely high. Li et al. reviewed 150 consecutive patients who had no reversible cause of AF.[34] They found that those not prescribed antiarrhythmic therapy had a significantly higher relapse rate with only 26% remaining in sinus rhythm at one year. The majority of recurrences occur in the first few weeks after cardioversion, probably as a result of atrial remodelling.[35] Some of the remodelling changes that occur in AF are related to changes in the L-type calcium current and calcium handling.[36] It has therefore been suggested that calcium antagonists may have a place at preventing remodelling but results from animal and human models are mixed.[37,38,39,40,41]

Metoprolol has been shown to maintain sinus rhythm after cardioversion, as have both sotalol and propafenone.[42,43] A comparison study suggested no additional advantage of sotalol over bisoprolol after cardioversion and highlighted the inherent risk of pro-arrhythmia with sotalol.[44] Quinidine has been shown to reduce recurrence rates of AF after cardioversion by 50% but a meta-analysis has pointed towards the potential increased mortality with use of this drug.[45]

There has been recent interest in the role of the reninangiotensin system in atrial electrical remodelling. Inhibition of endogenous angiotensin II by captopril or candesartan prevents the shortening of atrial refractory periods during rapid atrial pacing in dogs.[46] Enalapril prevented the structural and electrical changes that promote AF initiation in an experimental heart failure model.[47] Pedersen et al. demonstrated that treatment with the angiotensin-converting enzyme (ACE) inhibitor trandolapril reduced the risk of developing AF after myocardial infarction by 55% during long-term follow-up.[48] This difference could not be explained by differences in levels of potassium or left ventricular function. Patients on ACE inhibitors have also been noted to have an improved outcome from cardioversion.[49] Madrid et al. studied 154 patients undergoing cardioversion of persistent AF.[50] Seventy-five patients were randomised to amiodarone only and 79 were randomised to amiodarone plus irbesartan. At two months, 85% of patients were still in sinus rhythm on combination therapy compared with 63% in the amiodarone only group. It is theorised that blockade of angiotensin II prevents atrial electrical remodelling by decreasing atrial stretch, modulating refractoriness, interfering with ion currents, modifying sympathetic tone and stabilising electrolyte concentrations.[46]

Data from the first anti-arrhythmic drug substudy of AFFIRM were published recently.[51] The investigators demonstrated a clear superiority of amiodarone in achieving sinus rhythm at one year compared to all other drug types. In a comparison between amiodarone and class 1 agents in 222 patients, 62% of patients were successfully treated with amiodarone compared with 23% randomised to class 1 agents (p<0.001). Similarly, in 256 patients, 60% of patients were successfully treated with amiodarone compared to 39% of those randomised to sotalol (p=0.001). There is also evidence suggesting that the use of amiodarone after cardioversion reduces costs by preventing hospitalisations and reducing the need for repeat cardioversion procedures.[52] The side effects associated with the use of amiodarone may, however, reduce the expected benefits in quality of life.Use of low-dose amiodarone (100 mg) may reduce side effects but data on its long-term efficacy remain unknown.[53]

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