The Effect of Spironolactone on Ventricular Tachyarrhythmias in Patients With Implantable Cardioverter-Defibrillators

Abstract

Background-Previous studies have suggested that aldosterone blockade can reduce the incidence of ventricular tachycardia (VT) or ventricular fibrillation (VF) in patients with heart failure. The SPIronolactone to Reduce ICD Therapy (SPIRIT) trial was designed to test the hypothesis that spironolactone reduces the incidence of VT/VF in patients with implantable cardioverter-defibrillators (ICDs) who are at moderately high risk for recurrent VT/VF. Methods and Results-Ninety patients who had ICDs who were at moderately high risk for recurrent VT/VF and who were not candidates for spironolactone by current heart failure guidelines were randomized to receive spironolactone 25 mg daily or placebo in a double-blind fashion. All patients had previously received ICD therapy (shock or antitachycardia pacing) for VT/VF within 2 years of randomization or an ICD for secondary prevention of VT/VF within 6 months of randomization. The primary end point was time to first recurrence of VT/VF requiring ICD therapy. After a median follow-up of 35 months, the Kaplan-Meier probability estimates for VT/VF requiring ICD therapy were 68.7% in the placebo group and 84.7% in the spironolactone group. Compared with placebo, spironolactone was associated with a similar risk of VT/VF (hazard ratio, 1.01; 95% CI, 0.64-1.83; P=0.71). There was no significant difference between the median times to first VT/VF recurrence requiring ICD therapy in the 2 groups. Conclusions-In patients with ICDs who were at moderately high risk for recurrent VT/VF on account of a recent VT/VF event that was either sustained or treated by the ICD and who were not candidates for spironolactone by current heart failure guidelines, spironolactone did not delay the first recurrence of VT/VF or reduce the risk of recurrent VT/VF. (Circ Arrhythm Electrophysiol. 2012;5:739-747.)

Health-Related Quality of Life in the Spironolactone to Reduce ICD Therapy (SPIRIT) Trial

“…More detailed information about the SPIRIT trial design, recruitment, randomization and other clinical characteristics of the patients has been published. 7 There were initially 44 in the spironolactone group: 30 completed the 24-months of follow-up, with 8 drop-outs and 6 deaths ( Figure 1). In the placebo group there were initially 46: 30 completed the 24-months of followup, with 6 dropouts and 10 deaths.…”

“…Additional details about the study and the primary outcomes are published. 7 Patients were enrolled from the Portland Veterans Affairs Medical Center, Veterans Affairs Puget Sound Health Care System, Oregon Health and Science University, and the Little Rock Veterans Affairs Medical Center. The institutional review board or ethics committee at each site approved the protocol, and all patients provided written informed consent before enrollment.…”

“…The primary outcomes of the study have been reported and this hypothesis was not supported. 7 It has been demonstrated that patients who receive ICD shocks experience reduced QOL, 8 where an ICD shock is associated with reduced physical functioning and mental health.…”

Molecular targets of current and prospective heart failure therapies

“…There is a potential for cardioprotective use in MI 2. Despite encouraging experimental data on ventricular arrhythmias,2 26 27 a recent clinical trial in which spironolactone was administered for the purpose of preventing ventricular arrhythmias in HF patients with implantable cardioverter-defibrillator (ICD) did not show any therapeutic effect 28…”

No impact of mineralocorticoid receptor antagonists on long‐term recurrences of ventricular tachyarrhythmias

“…Furthermore, patients were usually not stratified by the presence or absence of an ICD 8 . Notably, there is only few data available whether MRA affects the risk of recurrent ventricular tachyarrhythmias in patients with systolic HF and prior ventricular tachyarrhythmias 10,11 …”