Log in to MyACC
Ranolazine in High-Risk ICD Patients - RAID
Contribution To Literature:
The RAID trial showed that ranolazine is not superior to placebo in reducing VT/VF among high-risk patients with an ICD and cardiomyopathy.
Description:
The goal of the trial was to assess the efficacy of ranolazine in reducing ventricular tachycardia (VT) and ventricular fibrillation (VF) or death in high-risk patients with an implantable cardioverter-defibrillator (ICD).
Study Design
Patients with either ischemic or nonischemic cardiomyopathy who had an ICD and were considered at high-risk for VT/VF were randomized in a 1:1 fashion to either ranolazine 1000 mg BID (n = 510) or placebo (n = 502).
- Total number of enrollees: 1,012
- Duration of follow-up: 27.4 months (median)
- Mean patient age: 64 years
- Percentage female: 18%
- Patients with diabetes: 33%
Inclusion criteria:
- Age ≥21 years
- On stable optimal pharmacologic therapy for their underlying cardiac condition
- High-risk patients defined as secondary prevention patients with an existing ICD/cardiac resynchronization therapy-defibrillator (CRT-D) after documented VT, VF, or cardiac arrest, regardless of when the implant was received; or primary prevention patients with a left ventricular ejection fraction ≤35% who have not experienced VT or VF treated with ICD therapy, but who had ≥1 of these additional high-risk criteria: blood urea nitrogen ≥26 mg/dl, QRS duration ≥120 ms, documented evidence of paroxysmal or persistent atrial fibrillation, nonsustained VT, or >500 premature ventricular contractions documented with 24-hour Holter recording
- Due to slow enrollment, broadened to include patients who received antitachycardia pacing (ATP) or shock, or had untreated nonsustained VT lasting ≥10 beats with heart rate ≥170 bpm
Exclusion criteria:
- QTc prolongation >550 ms
- Patients on agents known to prolong the QT interval
- Patients on potent and moderately potent CYP3A inhibitors or inducers
- Patients with chronic kidney disease with creatinine >2.5 mg/dl
Other salient features/characteristics:
- Atrial fibrillation: 19%
- Ischemic cardiomyopathy: 54%
- ICD for secondary prevention: 34%
- CRT-D: 42%
- On beta-blockers: 93%
- On antiarrhythmic drug(s): 16%
Principal Findings:
The primary endpoint, VT/VF requiring ICD therapy for ranolazine vs. placebo, was 34.1% vs. 39.4%, p = 0.12.
Secondary outcomes:
- VT/VF requiring ICD shock or death: 25.7% vs. 28.9%, p = 0.89
- Recurrent VT/VF requiring ATP or shock: 433 vs. 650, p = 0.028
- Cardiovascular hospitalization or death: 46.5% vs. 44.2%, p = 0.32
- Death: 13.7% vs. 15.5%, p = 0.87
- VT requiring ATP: 18.0% vs. 23.3%, p = 0.038
Drug discontinuation was high over the duration of follow-up: nearly 50% with ranolazine and 40% with placebo.
Interpretation:
Ranolazine is not superior to placebo in reducing VT/VF among high-risk patients with an ICD and cardiomyopathy. A reduction in recurrent VT/VF requiring ATP/shock, a prespecified secondary endpoint, is hypothesis-generating and will need to be assessed further. These findings need to be viewed within the limitation of poor drug adherence in this trial.
References:
Zareba W, Daubert JP, Beck CA, et al. Ranolazine in High-Risk Patients With Implanted Cardioverter-Defibrillators: The RAID Trial. J Am Coll Cardiol 2018;72:636-45.
Editorial Comment: Albert CM. Ranolazine in Patients With Implantable Cardioverter-Defibrillators: Ready for Prime Time? J Am Coll Cardiol 2018;72:646-9.
Keywords: Adrenergic beta-Antagonists, Arrhythmias, Cardiac, Atrial Fibrillation, Cardiac Resynchronization Therapy, Cardiomyopathies, Defibrillators, Implantable, Heart Arrest, Heart Failure, Primary Prevention, Risk, Secondary Prevention, Tachycardia, Ventricular, Ventricular Fibrillation, Ventricular Premature Complexes
< Back to Listings
