Antiarrhythmic drugs and NOACs: A common combination with under-recognised interaction
A 68-year-old male, with a history of cigarette smoking and high blood pressure, presented with atypical chest pain and palpitations. He was overweight (body mass index, 28kg/m2). Electrocardiogram (ECG) showed mild left ventricular hypertrophy (LVH), and echocardiogram showed moderate left atrial enlargement (4.5 cm), but no significant valvular heart disease. An ambulatory ECG documented paroxysmal atrial fibrillation (AF) with an average ventricular rate of 130 bpm. Coronary angiogram revealed a 60 percent narrowing of the circumflex artery, with normal fractional flow reserve. The coronary artery disease (CAD) was managed pharmacologically.
He was given the antiarrhythmic agent (AAD) sotalol (80 mg BID) and the non-vitamin K antagonist oral anticoagulant (NOAC) rivaroxaban (20 mg QD). However, he continued to experience brief but frequent AF episodes. As the patient preferred further conservative treatment, dronedarone (400 mg BID) was started. He responded well to dronedarone. There was no change in liver function or in QTc interval. Apixaban 5 mg BID was used instead of rivaroxaban.
There are 4 pillars in AF management: prevention of stroke and systemic embolism, rate control, rhythm control, and management of risk factors. NOACs are the most effective medication for stroke prevention, but their interaction with permeability glycoprotein (P-gp) and some cytochrome enzymes (e.g. CYP3A4) makes them susceptible to some interactions with both rate and rhythm controlling drugs.
The choice of AADs depends on the presence of CAD, cardiac function and drug safety. For example, class Ic AADs, such as flecainide and propafenone, are contraindicated in patients with underlying CAD, left ventricular hypertrophy, and congestive heart failure. The most potent AAD is amiodarone, but it can cause pulmonary toxicity and thyroid dysfunction.1
Dronedarone is recommended for the prevention of recurrent symptomatic AF in patients with stable CAD, non-pathological LVH and normal left ventricular function.1 Clinical trials have demonstrated the efficacy of dronedarone in reducing AF symptoms in patients with paroxysmal/persistent AF, and reduced cardiovascular (CV) hospitalisation and death in the ATHENA trial.2,3 (Table) However, it should not be used in patients with permanent AF and in those with impaired heart function.4,5 Concomitant use of digoxin, with its interaction with dronedarone might be the underlying reason.6 (Table)
As AADs are often combined with NOACs, potential drug interactions should be recognised. Amiodarone will increase the bleeding risk in patients on NOACs. Plasma concentration of NOACs will also increase with dronedarone.6
The European Heart Rhythm Association and ESC have made the following recommendations on concomitant use of dronedarone with currently available NOACs:1,7,8
· Observational data suggested that apixaban at the standard dose (5 mg BID) can be safely used with dronedarone, which was used in this case;
· Dabigatran 150 mg BID is contraindicated with dronedarone due to increased drug plasma concentration with concomitant administration (no pharmacokinetic data is currently available on the interaction between dronedarone and dabigatran 110 mg BID);
· A reduced dose of edoxaban (30 mg QD) is recommended when used concomitantly with dronedarone;
· With limited pharmacokinetic data, the concomitant use of dronedarone with rivaroxaban is not recommended
In summary, this case illustrates the effective and safe concomitant use of dronedarone with the NOAC apixaban in managing AF symptoms of an overweight patient with moderate CAD, left atrial enlargement and non-pathological LVH with preserved systolic function, who did not respond well to sotalol. In addition, the patient is currently undertaking weight reduction measures, which could help maintain sinus rhythm and improve the efficacy of AF ablation should the patient opt for or require this alternative therapy.