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.
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).
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%
- 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
- 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%
The primary endpoint, VT/VF requiring ICD therapy for ranolazine vs. placebo, was 34.1% vs. 39.4%, p = 0.12.
- 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.
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.
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.
Clinical Topics: Arrhythmias and Clinical EP, Heart Failure and Cardiomyopathies, Prevention, Implantable Devices, EP Basic Science, SCD/Ventricular Arrhythmias, Atrial Fibrillation/Supraventricular Arrhythmias, Acute Heart Failure
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
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