Comparison of Medical Therapy, Pacing and Defibrillation in Heart Failure - COMPANION

Feb 23, 2009
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Author/Summarized by Author:
Anthony A. Bavry, MD, MPH, FACC
Summary Reviewer:
Deepak L. Bhatt, MD, MPH, MBA, FACC
Summary Supplemental Reviewer:
Trial Sponsor:
Boston Scientific Corp, CRM
Date Presented:
01/01/2003
Date Published:
01/01/2009
Date Updated:
02/23/2009
Original Posted Date:
02/23/2009
References

Description:

The goal of the COMPANION trial was to compare optimal pharmacological therapy (OPT) with chronic resynchronization therapy (CRT), or CRT with defibrillator (CRT-D) in patients with advanced chronic heart failure (CHF).

Hypothesis:

CRT or CRT-D would reduce mortality and major morbidity in subjects with New York Heart Association (NYHA) class III or IV CHF and QRS width ≥120 ms, due to an ischemic or nonischemic cardiomyopathy.

Study Design

  • Randomized
  • Parallel

Patients Enrolled: 1,520
NYHA Class: 85% class III; 15% class IV
Mean Follow Up: Median 14.4 months
Mean Patient Age: 67 years
Female: 32%
Mean Ejection Fraction: 22%

Patient Populations:

  • HF hospitalization within the past 12 months
  • NYHA class III or IV CHF and QRS width ≥120 ms due to an ischemic or nonischemic cardiomyopathy
  • PR interval >150 ms
  • Ejection fraction <35%

Primary Endpoints:

  • Time to all-cause mortality or all-cause nonelective hospitalization

Secondary Endpoints:

  • Total survival
  • Cardiac morbidity
  • Quality of life
  • Exercise performance

Drug/Procedures Used:

Subjects were randomized 1:2:2 open-label to: 1) OPT, 2) CRT + OPT, and 3) CRT-D + OPT. OPT was diuretics, angiotensin-converting enzyme inhibition (ACE-I) or angiotensin receptor blocker (ARB) substitution, β-blockade, and spironolactone; use of digoxin was optional.

Concomitant Medications:

90% on ACE-I or ARB, 68% on beta-blocker, 55% on spironolactone

Principal Findings:

The trial was planned to include 2,200 patients; however, the Data Safety and Monitoring Board discontinued the trial early after the enrollment of 1,520 patients, due to superior efficacy of the primary endpoint in the CRT and CRT-D arms.

The primary endpoint of all-cause mortality or all-cause hospitalizations occurred in 68% of patients in the OPT arm, and was 56% in the CRT + OPT arm (hazard ratio [HR] 0.81, p = 0.015) and 56% in the CRT-D + OPT arm (HR 0.80, p = 0.010). Mortality alone through 1 year was 19% in the OPT arm, and was marginally reduced in the CRT arm (HR 0.76, p = 0.06) and reduced in the CRT-D arm (HR 0.64, p = 0.003). The rate of the combined endpoint of time to mortality or heart failure hospitalization was 60% in the OPT arm and was reduced with CRT (HR 0.75, p = 0.002) and with CRT-D (HR 0.72, p < 0.001). Similar treatment effects were seen in all subgroup analyses.

In the device arms, the implantation success rate was 87% in the CRT arm and 91% in the CRT-D arm. Serious adverse event rates were 10% and 8%, respectively.

After accounting for competing risks, CRT and CRT-D still reduced all-cause hospital admissions by 21% and 25%, respectively.

Interpretation:

Among patients with advanced CHF, treatment with CRT or CRT-D was associated with a reduction in the composite of all-cause mortality or all-cause hospitalizations at a median follow-up of 14 months. The trial was discontinued early, due to the superior efficacy in the resynchronization arms.

Early trials have shown an improvement in the endpoints of quality of life, exercise capacity, and functional class with resynchronization in HF patients. However, this is the first large, randomized trial to show an improvement in all-cause mortality and rehospitalizations with resynchronization therapy and implantable cardioverter defibrillator use in severe HF patients.

The patient population was highly selective (severe HF defined by NYHA class III-IV with left ventricular dysfunction and wide QRS of ≥120 ms), and may not be generalizable to other lower-risk HF patients.

References:

Anand IS, Carson P, Galle E, et al. Cardiac resynchronization therapy reduces the risk of hospitalizations in patients with advanced heart failure. Results from the comparison of medical therapy, pacing and defibrillation in heart failure (COMPANION) trial. Circulation 2009;119:969-77.

Bristow MR, et al. Cardiac-Resynchronization Therapy with or without an Implantable Defibrillator in Advanced Chronic Heart Failure. N Engl J Med 2004;350:2140-50.

Presented at Late-Breaking Clinical Trials, ACC 2003.

Presented at the European Society of Cardiology, Vienna, Austria, September 2003.

Keywords: Angiotensin Receptor Antagonists, Digoxin, Diuretics, Spironolactone, Receptors, G-Protein-Coupled, Proto-Oncogene Proteins, Quality of Life, Cardiomyopathies, Heart Failure, Hospitalization, Ventricular Dysfunction, Left, Defibrillators, Implantable


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