Authors
Bristow MR, Saxon LA, Boehmer J, et al.
Title
Cardiac-Resynchronization Therapy with or without an Implantable Defibrillator in Advanced Chronic Heart Failure
References
N Engl J Med 2004;350:2140-50.
Background
Dyssynchonous left ventricular contraction reduces systolic function and increases systolic volume. However, resynchronization by biventricular stimulation has been shown to improve ejection fraction and improve heart failure symptoms. At the time of the initiation of the study, the impact of treatment with ICD and CRT in advanced heart failure was not established.
Purpose
To determine if CRT therapy with or without ICD improves survival and decreases hospitalizations in advanced heart failure (HF) patients with a prolonged QRS interval and on optimal medication therapy.
Design
  • Multicenter, randomized, open-label, controlled trial
  • 1520 patients with NYHA class III or IV heart failure, LVEF ≤35%, a QRS duration >120 msec, PR interval >150 msec, sinus rhythm, no clinical indication for pacemaker or implantable defibrillator, and heart failure hospitalization within the last year
  • Receiving a diuretic, ACE inhibitor or ARB, a β-blocker (unless did not tolerate or contraindicated) and spironolactone (unless not tolerated). Digoxin and other HF medications also permitted at investigator’s discretion
Exclusion Criteria
  • Pacemaker or defibrillator, cardiac or cerebral ischemic event within the last 3 months, atrial arrhythmias in the last month, SBP >170 or <80 mmHg, heart rate >140 bpm, serum creatinine >265.2 µmol/L, serum aminotransferase level more than three times the upper limit of normal.
Follow-Up
23 months (stopped prematurely, according to prespecified rules)
Treatment Regimen
  • randomized in 1:2:2 ratio respectively to:
    • Optimal medical therapy (MED group) vs.
    • Optimal medical therapy + CRT with pacemaker (MED+CRT-P group) vs.
    • Optimal medical therapy + CRT with pacemaker-defibrillator (MED+CRT-D)
Results

Primary Endpoints

Composite of all cause death or all cause hospitalization (at 12 months):

  • 68% (MED) vs. 56% (MED+CRT-P), HR 0.81 (0.69-0.96), p=0.014
  • 68% (MED) vs. 56% (MED+CRT-D), HR 0.80 (0.68-0.95), p=0.01

Secondary Endpoints (see study for complete list)

All cause death (at 12 months):

  • 19% (MED) vs. 15% (MED+CRT-P), HR 0.76 (0.58-1.01), p=0.059
  • 19% (MED) vs. 12% (MED+CRT-D), HR 0.64 (0.48-0.86), p=0.003

Moderate-Severe Adverse Events:

  • 61% (MED) vs. 66% (MED+CRT-P), p=0.15
  • 61% (MED) vs. 69% (MED+CRT-D), p=0.03

Additional Outcomes (not pre-specified)

Death from or hospitalization from CV causes:

  • 60% (MED) vs. 45% (MED+CRT-P), HR 0.75 (0.63-0.90), p=0.002
  • 60% (MED) vs. 44% (MED+CRT-D), HR 0.72 (0.60-0.86), p<0.001

Death from or hospitalization from heart failure:

  • 45% (MED) vs. 31% (MED+CRT-P), HR 0.66 (0.53-0.87), p=0.002
  • 45% (MED) vs. 29% (MED+CRT-D), HR 0.60 (0.49-0.75), p<0.001
    • In MED group, events compromised of: 24% HF death, 72% HF hospitalization, 4% need for iv inotropes or vasoactive drugs for >4hrs
Summary
In patients with advanced, symptomatic HF with a wide QRS interval and receiving optimal medication therapy, CRT with or without a defibrillator reduces the risk of combined all cause death or all cause hospitalizations as compared to optimal medication therapy. CRT with a ICD increases survival rates as compared to optimal medication therapy.