Article

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

Heart and Vascular Research Center, Hamann 3rd Floor, MetroHealth Campus, Case Western Reserve University, 2500 MetroHealth Drive, Cleveland, Ohio 44109-1998, USA.
Journal of the American College of Cardiology (Impact Factor: 14.09). 09/2004; 44(6):1276-82. DOI: 10.1016/j.jacc.2004.06.052
Source: PubMed

ABSTRACT 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.
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.
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.
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).
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.

0 Bookmarks
 · 
71 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: The potent and efficacious anti-dysrhythmic agent amiodarone (AM) can cause potentially life-threatening lung damage (amiodarone-induced pulmonary toxicity; AIPT), which is characterized by cell death in the lungs, followed by inflammation and fibrosis. AM's major metabolite, desethylamiodarone (DEA), has a greater toxic potency than AM and it has been suggested that DEA may act synergistically with AM to cause lung toxicity. The objective of this study was to determine the type of cytotoxic interaction between AM and DEA in HPL1A human peripheral lung epithelial cells. Cytotoxicity was measured by lactate dehydrogenase release. AM and DEA caused concentration-dependent cytotoxicity in HPL1A cells. The concentration of drug causing 50% cell death (LC50) and the Hill slope factor, which represents steepness of the concentration-cell death curve, were significantly different between AM and DEA (12.4 μM and 1.98; 5.07 μM and 5.43, for AM and DEA, respectively) indicating that they may induce cytotoxicity through different mechanisms. A combined concentration of 7.13 μM AM plus DEA, equivalent to 41% of each compound's individual LC50 value, resulted in 50% cell death. Isobolographic analysis revealed this effect to be additive, although the combined concentrations were only slightly higher than the concentrations that defined the threshold of synergy (threshold of synergy = 4.21±1.98 μM AM plus 1.73±1.05 μM DEA; experimental data point = 5.06±0.47 μM AM plus 2.07±0.47 μM DEA). The cytotoxic interaction between AM and DEA may be clinically relevant in the development of AIPT.
    Chemico-biological interactions 05/2013; · 2.46 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The prevalence of atrial fibrillation substantially increases after 70 years of age. However, the effect of rate-control versus rhythm-control strategies on outcomes in these patients remains unclear. In the randomized Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) trial, 4060 patients (mean age 70 years, range 49-80 years) with paroxysmal and persistent atrial fibrillation were randomized to rate-control versus rhythm-control strategies. Of these, 2248 were 70-80 years, of whom 1118 were in the rate-control group. Propensity scores for rate-control strategy were estimated for each of the 2248 patients and were used to assemble a cohort of 937 pairs of patients receiving rate-control versus rhythm-control strategies, balanced on 45 baseline characteristics. Matched patients had a mean age of 75 years; 45% were women, 7% were nonwhite, and 47% had prior hospitalizations due to arrhythmias. During 3.4 years of mean follow-up, all-cause mortality occurred in 18% and 23% of matched patients in the rate-control and rhythm-control groups, respectively (hazard ratio [HR] associated with rate control, 0.77; 95% confidence interval [CI], 0.63-0.94; P = .010). HRs (95% CIs) for cardiovascular and noncardiovascular mortality associated with rate control were 0.88 (0.65-1.18) and 0.62 (0.46-0.84), respectively. All-cause hospitalization occurred in 61% and 68% of rate-control and rhythm-control patients, respectively (HR 0.76; 95% CI, 0.68-0.86). HRs (95% CIs) for cardiovascular and noncardiovascular hospitalization were 0.66 (0.56-0.77) and 1.07 (0.91-1.27), respectively. In septuagenarian patients with atrial fibrillation, compared with rhythm-control, a rate-control strategy was associated with significantly lower mortality and hospitalization.
    The American journal of medicine 10/2013; 126(10):887-93. · 5.30 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Atrial fibrillation (AF) is common in ICU patients and is associated with a two- to fivefold increase in mortality. This paper provides a reappraisal of the management of AF with a special focus on critically ill patients with haemodynamic instability. AF can cause hypotension and heart failure with subsequent organ dysfunction. The underlying mechanisms are the loss of atrial contraction and the high ventricular rate. In unstable patients, sinus rhythm must be rapidly restored by synchronised electrical cardioversion (ECV). If pharmacological treatment is indicated, clinicians can choose between the rate control and the rhythm control strategy. The optimal substance should be selected depending on its potential adverse effects. A beta-1 antagonist with a very short half-life (e.g., esmolol) is an advantage for ICU patients because the effect of beta-blockade on cardiovascular stability is unpredictable in those patients. Amiodarone is commonly used in the ICU setting but has potentially severe cardiac and noncardiac side effects. Digoxin controls the ventricular response at rest, but its benefit decreases in the presence of adrenergic stress. Vernakalant converts new-onset AF to sinus rhythm in approximately 50% of patients, but data on its efficacy and safety in critically ill patients are lacking.
    Critical care research and practice 01/2014; 2014:840615.

Full-text

View
0 Downloads
Available from