Atrial fibrillation (AF) is the most recurrent arrhythmia in clinical practice. It affects more than two million people in the US, with 180,000 new cases added every year. It is estimated that by the year 2050, there will be approximately six to eight million people suffering from AF.

       In the past, AF was considered just a nuisance. Patients were advised to learn how to live with it. Digoxin, and later beta blockers, were the drugs of choice to achieve rate control. We now know that AF is not just a nuisance. In fact, it is a serious problem with major and devastating complications.
       Although AF is commonly known to be an affliction of growing old, there are almost 100,000 people in the US who are 40 years of age or younger suffering from this arrhythmia. In this group of patients, AF can have negative and debilitating effects on their quality of life.
       People with AF have a 2–5% yearly chance of having a stroke than those who do not have AF. This percentage increases with age, to about 10% in those who are 65 or above. In the US, it is estimated that mortality caused by AF is approximately 10,000 per year, mainly from stroke.
       In AF, since the atria “quiver” rather than contract, blood may pool, causing a thrombus to form and a stroke to happen. Anticoagulation has become a standard therapy for AF to minimize the risk of stroke. However, anticoagulation does not entirely eliminate that risk. It is believed that even when people do not suffer from stroke or TIA while in AF, micro-embolic events can occur causing subtle memory changes and dementia.
       In addition to the risk of stroke, persistent atrial fibrillation over time can lead to tachycardia-induced cardiomyopathy and heart failure (Figure 1).

Figure 1.

Classification of AF (Figure 2)

Figure 2.

       Over the last few decades, management of AF has evolved from our understanding of the risks associated with it. (Figure 3)

Figure 3.

Each of the options presented in Figure 3 aims at reducing or eliminating the patient’s symptoms and the risks associated with AF, mainly stroke and cardiomyopathy. The options adopted vary from one practice to the other, and treatment may include one or more of these options combined.
       In this article, we will focus on the option of rhythm control with anti-arrhythmics (AA) — mainly, the new generation of class 1C agents.
       Figure 4 shows the most commonly used AA for rhythm control and maintaining normal sinus rhythm (NSR).

Figure 4.

Class 1C AA (Figure 5)

Figure 5.

       The class 1C AA are a relatively new group of agents; they act by blocking the sodium channel (prolonging QRS), and have little effect on repolarization (no effect on QT interval). However, because of their negative inotropic effect, they are not recommended for patients with structural heart disease.
       In the landmark study CAST (Cardiac Arrhythmia Suppression Trial), it was shown that patients with coronary artery disease and poor left ventricular function (EF < 40%) are at risk of developing proarrhythmia with class 1C antiarrhythmic agents.
       The ACC/AHA have established guidelines for the use of AA in patients with AF. The guidelines clearly distinguish between patients with heart disease and those without (Figure 6).

Figure 6.

       Class 1C can be used safely and effectively in those patients without structural heart disease. In patients with hypertension, LVH should be documented to be less than 1.4 cm before a class 1C can be used.
       Almost one-third of patients diagnosed with AF have what is known as “lone atrial fibrillation.” This type of AF is not associated with the presence of structural heart disease (Figure 7).

Figure 7.

       In the US, almost 400,000 patients are hospitalized every year with the primary diagnosis of AF. It is estimated that half of these patients have lone AF, i.e. no ischemic heart disease or congestive heart failure. Those patients are considered good candidates for using class 1C AA. They are usually active and relatively young, and AF may greatly affect their quality of life.

Rythmol and Rythmol SR
       Rythmol (propafenone), a class 1C antiarrhythmic drug, has been widely used for ventricular and supraventricular arrhythmias since 1980. Because of its rapid absorption from the gut, Rythmol is recommended to be taken three times daily. Recently, Rythmol SR (sustained release) was introduced; to be taken twice a day rather than three times a day. Figure 8 shows a comparison between Rythmol and Rythmol SR.

Figure 8.

       The RAFT study (Rythmol Atrial Fibrillation Trial) was a randomized, double-blinded, placebo-controlled clinical trial to test the efficacy and safety of the sustained-release preparation of Rythmol SR in reducing the frequency of symptomatic arrhythmia recurrences in patients with atrial fibrillation. Patients with a history of symptomatic AF who were in sinus rhythm were randomly assigned to receive placebo or propafenone SR 425, 325, or 225 mg twice a day (Figure 9 and 10).

Figure 9.

Figure 10.

       As shown in Figure 11, propafenone SR significantly lengthened the time to the first symptomatic atrial arrhythmia recurrence at all three doses compared with placebo.

Figure 11.

       In addition, the study showed that Rythmol SR did not appear to increase the recurrence of regular supraventricular tachycardia as atrial flutter (something which was widely reported when class 1C was initially introduced). Rythmol SR also did not appear to increase the occurrence of asymptomatic AF as evident by Holter monitoring.

Rythmol SR Dosing
       Rythmol SR comes in three strengths: 225, 325, and 425 mg. Dosage should be titrated according to patient’s response and tolerance. It is usually started at 225 mg every 12 hours. If the therapeutic effect is not achieved (e.g. occurrence of daily AF episodes), the dose can be increased to 325 mg every 12 hours at a minimum of five days after the initial dose of 225 mg. The same pattern is repeated if the higher dose of 425 mg is needed.

Adverse Effects of Rythmol SR
       The adverse effects of Rythmol SR are dose related. In the RAFT study, the most common adverse effects were reported to be: dizziness, fatigue, palpitations, taste disturbance, nausea, GI upset and constipation. These symptoms commonly occur in the first 7–14 days after initiation of therapy.
       Other severe adverse effects are less common and may include: severe bradycardia, especially if used in combination with beta blockers or calcium channel blockers, and also hypotension, heart block or proarrhythmia.
       Since Rythmol SR is highly metabolized by the liver, it should be used with caution in patients with liver impairment. Rythmol SR and other class 1C antiarrhythmics are contraindicated in patients with congestive heart failure, ischemic heart disease and those with poor left ventricular function.
       Due to the beta-adrenergic-blocking property of Rythmol, it should not be administered to patients with chronic bronchitis or emphysema. Figure 12 shows a complete list of contraindications of Rythmol SR.

Figure 12.

Conclusion
       Rythmol SR is a new class 1C antiarrhythmic agent that has proved its safety and efficacy in the treatment of atrial fibrillation. It is indicated to prolong the time to recurrence of symptomatic AF episodes in those patients with no structural heart disease. Other benefits of Rythmol SR are summarized in Figure 13.

Figure 13.