Risk of proarrhythmic events in the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) study: a multivariate analysis.

OBJECTIVES: This study examined the risk of proarrhythmic events in patients receiving antiarrhythmic drugs for treatment of atrial fibrillation (AF) according to present-day safety guidelines. BACKGROUND: Advances in understanding the proarrhythmic risk of antiarrhythmic drugs has led to development of safety guidelines for these agents. Such guidelines were used in the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) study. METHODS: This study was an analysis of the risk of arrhythmic events (arrhythmic death, resuscitated cardiac arrest, sustained ventricular tachycardia (VT), and torsade de pointes VT) in the antiarrhythmic drug arm of the AFFIRM study. Each time an antiarrhythmic drug was begun, it was counted as an exposure to that drug and the risk of an arrhythmic event was calculated. RESULTS: A total of 2,033 patients received 3,030 exposures to antiarrhythmic drugs. Ninety-six arrhythmic events occurred by six years. Patients with a left ventricular ejection fraction <40% had more arrhythmic events. Twelve documented cases of torsade de pointes VT were noted. The incidence of torsade de pointes was 0.6% at five years (95% confidence interval 0.32 to 1.07). CONCLUSIONS: The overall risk of adverse arrhythmic events upon exposure to antiarrhythmic drugs in the AFFIRM study was reasonably low. Strict criteria for the safe use of antiarrhythmic drugs were successful in minimizing proarrhythmic events.

Effect of nesiritide (B-type natriuretic peptide) and dobutamine on ventricular arrhythmias in the treatment of patients with acutely decompensated congestive heart failure: the PRECEDENT study.

BACKGROUND: Dobutamine is commonly used as a means of treating decompensated congestive heart failure (CHF). Although typically effective at improving short-term hemodynamics and symptomatology, the frequent occurrence of arrhythmias and tachycardia is undesirable. In this randomized, multicenter trial, we compared the safety and clinical effectiveness of the cardiac hormone nesiritide (human B-type natriuretic peptide) with dobutamine in hospitalized patients with decompensated CHF. METHODS: The study population consisted of 255 patients who were randomized to 1 of 2 doses of intravenous nesiritide (0.015 or 0.03 microg/kg/min) or dobutamine (> or =5 microg/kg/min) and stratified by means of an earlier history of ventricular tachycardia. Patients were also assessed with 24 hour Holter recordings immediately before and during study drug therapy and by means of signs and symptoms of CHF. RESULTS: Dobutamine significantly increased the mean (1) number of ventricular tachycardia events per 24 hours by 48 +/- 205 (P =.001), (2) repetitive ventricular beats per hour by 15 +/- 53 (P =.001), (3) premature ventricular beats per hour by 69 +/- 214 (P =.006), and (4) heart rate by 5.1 +/- 7.7 beats per minute (P <.001). These end points were significantly decreased or unchanged in the nesiritide groups. Nesiritide did not increase heart rate, despite a greater reduction of blood pressure. Both drugs were similarly effective means of improving signs and symptoms of CHF. CONCLUSIONS: Dobutamine is associated with substantial proarrhythmic and chronotropic effects in patients with decompensated CHF, whereas nesiritide actually reduces ventricular ectopy or has a neutral effect. Compared with dobutamine, nesiritide may be a safer, short-term treatment for patients with decompensated CHF.

Inhibition of angiotensin II signaling and recurrence of atrial fibrillation in AFFIRM.

OBJECTIVES: We investigated whether inhibition of endogenous angiotensin II signaling reduces the recurrence rate of atrial fibrillation (AF) in patients enrolled in the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) study. BACKGROUND: Structural and electrical remodeling contribute to AF. Previous experimental studies have implicated the angiotensin II signaling pathway in this process, and recent clinical evidence supports a beneficial effect of inhibiting angiotensin II activity. METHODS: Using the AFFIRM database, we retrospectively identified a cohort of patients randomized to the rhythm-control arm who were in sinus rhythm. Exposure to angiotensin II receptor blockers or angiotensin-converting enzyme inhibitors (ANGI) was determined, and the time to first recurrence of AF was compared between ANGI users and nonusers. RESULTS: The study cohort included 732 patients not taking ANGI through the initial 2-month follow-up and 421 patients taking ANGI during this time. Patients in the ANGI group more likely had hypertension, diabetes, coronary artery disease, and congestive heart failure compared to patients not taking ANGI. Risk of AF recurrence in the ANGI treatment group did not differ from the risk observed in patients not taking the drugs (hazard ratio [HR] = 0.91, 95% confidence interval [CI] = 0.77-1.09). However, in patients with congestive heart failure or impaired left ventricular function, ANGI use was associated with a lower risk of AF recurrence. CONCLUSIONS: This analysis provides evidence that ANGI use may be beneficial in some patient subgroups with AF and underscores the need for randomized clinical trials defining more fully the role of angiotensin II inhibition in treating AF.