Ranolazine in High-Risk ICD Patients - RAID

Jul 31, 2018
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Author/Summarized by Author:
Dharam J. Kumbhani, MD, SM, FACC
Summary Reviewer:
Deepak L. Bhatt, MD, MPH, MBA, FACC
Trial Sponsor:
Grants from National Heart, Lung, and Blood Institute.
Date Published:
07/30/2018
Date Updated:
07/31/2018
Original Posted Date:
07/31/2018
References

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.

Clinical Topics: Arrhythmias and Clinical EP, Cardiovascular Care Team, 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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