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The Place of Antiarrhythmic Drugs and Rhythm Control in the Treatment of Atrial Fibrillation
Atrial Fibrillation and Structural Heart Disease may be beneficial,
6
and this ‘pill-in-the-pocket’ approach has been
Many patients with AF present with concurrent cardiovascular shown to be safe in outpatients, with high patient compliance, a low
conditions such as left ventricular hypertrophy, coronary artery disease, incidence of adverse events and a marked reduction in emergency
or heart failure. Out of 17,949 adults with AF enrolled in the room visits and hospitalisations.
66
Although flecainide has been shown
Anticoagulation and Risk Factors in Atrial Fibrillation (ATRIA) study, 49% to be one of the most effective drugs in cardioversion to sinus rhythm,
had hypertension, 29% were diagnosed with heart failure and 35% had with a success rate of 77–93%,
67–70
efficacy is lost if the arrhythmia is
a history of coronary heart disease.
1
Similar findings of a high prevalence present for more than 24 hours,
68,69
a phenomenon proposed to result
of comorbid conditions have also been reported in other trials. Of the from electrical remodelling.
71
However, intervention with intravenous
4,060 patients enrolled in AFFIRM, 51% were hypertensive, 26% had flecainide early in AF recurrence (<10 hours) in patients who had
coronary artery disease, 5% had valvular disease and 23% had a history previously failed pharmacological cardioversion and had undergone
of congestive heart failure. Only 12% were found to be free of any electrical cardioversion has been shown to successfully restore
apparent cardiac disease.
29
In FRACTAL, where baseline criteria were efficacy in 58% of cases of recurrent AF.
72
This small window of
analysed in 963 patients, 49% had hypertension, 25% had coronary opportunity necessitates strict rhythm monitoring, however. The pill-in-
artery disease, 17% had valvular disease and 18% had heart failure.
63
the-pocket approach has been proposed to reduce the interval
between arrhythmia onset and treatment. Moreover, this approach has
Concomitant structural heart disease is a frequent accompanying been proposed to be beneficial for patients with recurrent episodes of
and/or underlying factor of AF, and can present an increased risk of symptomatic AF, as such episodic therapy can reduce the risk of toxicity
proarrhythmic events. Since the CAST trials in which class Ic drugs were compared with sustained therapy.
6
Early treatment, alongside the lower
found to have detrimental effects on the wellbeing and survival of likelihood of structural heart disease in younger patients, could then
patients with concurrent cardiovascular conditions,
52
studies evaluating potentially increase the long-term efficacy of therapy.
antiarrhythmic drugs in AF have greatly focused on cardiac safety. It
follows that the identification of heart disease in patients with AF is It is possible that the low use of class Ic drugs is an ongoing result of the
extremely important, and that cardiac disease, if present, is an obvious fall-out from the CAST study data, but there remains a need to
point of consideration in selecting the appropriate antiarrhythmic agent. emphasise the important role of this drug class in patients with no or
Although amiodarone is recommended for use in patients with heart minimal structural heart disease, as the safety advantage of these drugs
failure or substantial left ventricular hypertrophy, amiodarone continues in this patient population cannot be denied. Clinical studies have found
to be used excessively in the treatment of AF, even in cases in which flecainide and propafenone to be similar in the number of patients who
other antiarrhythmic agents are better suited and indicated for as first- convert to sinus rhythm,
73,74
although the studies have found the relative
line therapy in the guidelines – highly contradictive considering the rates of conversion to be inconsistent.
73,74
Rates and severity of adverse
emphasis on cardiac safety. Amiodarone has been shown to induce a effects have also been similar between the two drugs.
73–75
One study has
number of clinically significant extracardiac effects, particularly over a stated that the adverse events experienced with propafenone were
long period of use, including pulmonary and liver toxicity, thyroid important enough to stop therapy, such that the probability of a patient’s
imbalances, photosensitivity, neuropathy and blindness; all of these compliance at one year tended to be higher with flecainide than with
adverse events are absent in sotalol, dofetilide and the class Ic agents propafenone.
76
While both drugs have demonstrated efficacy and safety,
flecainide and propafenone. Indeed, a meta-analysis comparing it is ultimately the clinician’s choice to use either flecainide or
amiodarone and class Ic drugs for termination of recent AF concluded propafenone, based on the drug’s safety and tolerability profile and the
that the efficacies were similar, and all were suitable for use as an amount of clinical experience, dosage and compliance considerations
alternative therapy for patients in whom class Ic and other more rapidly and clinical data available with each drug.
acting drugs cannot be used.
64
It is important for clinicians to understand
the inter-relationships between structural heart disease and Conclusions
antiarrhythmic drugs not only in terms of proarrhythmic risk, but also in AF is a complicated condition with a significant impact on morbidity and
terms of safety and toxicities. mortality. With the potential to develop an increased risk of
thromboembolism and irreversible structural changes to the heart, it
Antiarrhythmic Drug Selection in the appears that rhythm control with antiarrhythmic drugs early in the
Absence of Structural Heart Disease disease course could be beneficial. Although rate control may be better
Patients with lone AF, or AF with minimal structural heart disease, are suited for elderly patients with structural heart disease, younger patients
candidates for class Ic drugs or sotalol, although in this setting sotalol with healthier hearts deserve rhythm control at an early stage following
has a small risk of torsades de pointes. Flecainide and propafenone are diagnosis. The class Ic drugs have proved useful in this population of
highly effective in the termination of AF in patients without structural patients, although adherence to guideline recommendations is poor and
heart disease, with differing rates of success depending on whether the other more dangerous drugs continue to be prescribed in lieu of the safer
preparation is oral (50–80%) or intravenous (90%).
65
Notably, these drugs first-line agents. With the emphasis on cardiac safety, one would expect
are generally well tolerated and are essentially devoid of extracardiac cardiologists to then select the best appropriate drug for their patients
organ toxicity. The guidelines state that the ability of this patient based on the type and severity of heart disease, concomitant disease,
population to administer these agents orally in an outpatient setting patient characteristics and long-term safety of the drug in question. ■
1. Go AS, et al., Prevalence of diagnosed atrial fibrillation in death: the Framingham Heart Study, Circulation, subjects (the Cardiovascular Health Study), Am J Cardiol,
adults: national implications for rhythm management and 1998;98:946–52. 1994;74:236–41.
stroke prevention: the AnTicoagulation and Risk Factors in 3. Ho KK, et al., The epidemiology of heart failure: the 5. Friberg J, et al., Rising rates of hospital admissions for atrial
Atrial Fibrillation (ATRIA) Study, JAMA, 2001;285:2370–75. Framingham Study, J Am Coll Cardiol, 1993;22:6A–13A. fibrillation, Epidemiology, 2003;14:666–72.
2. Benjamin EJ, et al., Impact of atrial fibrillation on the risk of 4. Furberg CD, et al., Prevalence of atrial fibrillation in elderly 6. Fuster V, et al., ACC/AHA/ESC 2006 Guidelines for the
EUROPEAN CARDIOLOGY 39
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