Author + information
- Received December 13, 1985
- Revision received March 18, 1986
- Accepted April 2, 1986
- Published online September 1, 1986.
- ↵§Address for reprints: Joel Morganroth, MD, Likoff Cardiovascular Institute, Hahnemann University Hospital, Broad and Vine Streets, Philadelphia, Pennsylvania 19102.
Antiarrhythmic therapy is known to be associated with a significant risk of adverse cardiac reactions, including a proarrhythmic response. This study assessed in 1,330 patients followed up for 292 ± 393 days the predictive value for cardiovascular safety of a system by which patients were classified according to ventricular arrhythmias on entry, presence or absence of organic heart disease and drug dose for flecainide acetate. Baseline arrhythmia subgroups included patients with 1) premature ventricular complexes only, 2) nonsustained ventricular tachycardia, and 3) sustained ventricular tachycardia.
Proarrhythmic events occurred in 6.8% of patients overall and were serious in 2.3% and lethal in 1.0%. However, proarrhythmia was highly dependent on arrhythmia class on entry: serious nonlethal proarrhythmic events occurred in 6.6% of patients with sustained ventricular tachycardia, only 0.9% with nonsustained ventricular tachycardia and 0% with premature ventricular complexes (p < 0.01). Proarrhythmic death occurred in 3.1% of patients with sustained ventricular tachycardia, 0.2% with nonsustained ventricular tachycardia and 0% with premature ventricular complexes only (p < 0.01). Proarrhythmia was also influenced by the presence of structural heart disease: serious nonlethal proarrhythmia occurred in 2.6% of patients with versus 0.4% of those without organic heart disease, and death occurred in 1.2 versus 0%, respectively. These adverse events were also dependent on dosing regimen. Flecainide caused premature discontinuation due to new or worsened heart failure in 1.4% of patients, all with underlying organic heart disease; however, heart failure was not clearly related to dose or type of arrhythmia. Symptomatic conduction disturbances occurred in 2.2%, and were predicted by preexistent sinus node disease but not by other baseline features.
The safety of flecainide was markedly enhanced by a slow, incremental approach to dosing, especially in high risk patients. Because most proarrhythmia occurred early during dose finding, hospitalization for drug initiation would appear to improve safety in patients with sustained ventricular tachycardia, heart failure and sinus node dysfunction. These data confirm the usefulness of a clinical classification system based on severity of rhythm disorder and presence of structural heart disease in predicting serious adverse proarrhythmic events with flecainide.
- Received December 13, 1985.
- Revision received March 18, 1986.
- Accepted April 2, 1986.
- American College of Cardiology Foundation