Lessons Learned and Insights Gained in the Design, Analysis, and Outcomes of the COMPANION Trial.
COMPANION (Comparison of Medical Therapy, Pacing and Defibrillation in Heart Failure), the first cardiac resynchronization therapy (CRT)-heart failure mortality and morbidity controlled clinical trial planned, conducted, and reported, was a randomized, 3-arm study that compared CRT delivered by a biventricular pacemaker (CRT-P) or a CRT defibrillator device (CRT-D) with optimal pharmacological therapy alone. The patient population had advanced chronic heart failure with QRS interval prolongation ≥120 ms and reduced left ventricular ejection fraction (heart failure with reduced ejection fraction). COMPANION had a composite hospitalization and mortality endpoint as the primary outcome measure but was also powered for mortality as the first secondary endpoint. The conduct of COMPANION was challenged by important issues that arose during the trial, the most important of which was U.S. Food and Drug Administration approval of CRT devices. Along with other challenges, this issue was appropriately dealt with by the Steering Committee and the Data and Safety Monitoring Committee and did not negatively affect trial results or conclusions. The authors report here updated analyses from the study, which are consistent with previously published results indicating that CRT-P or CRT-D has favorable effects on heart failure morbidity and mortality in a patient population "precision" selected by the surrogate marker of increased QRS interval duration. New analyses indicate that increasing the number of classes of neurohormonal inhibitor concurrent therapy has a positive effect on CRT mortality reduction. Hypothesis-generating new findings are that in patients receiving beta-blocker therapy, the mortality reduction advantage of CRT-D versus CRT-P may be minimized or eliminated and that there may be adverse effects of CRT-D defibrillator shocks on pump failure-related outcomes.
University of Colorado, Aurora and Boulder, Colorado. Electronic address: michael.bristow@ucdenver.edu.
Michael R
MR
Bristow
University of Southern California, Los Angeles, California.
Leslie A
LA
Saxon
Temple University, Philadelphia, Pennsylvania.
Arthur M
AM
Feldman
University of Wisconsin, Madison, Wisconsin.
Chaoqun
C
Mei
University of Wisconsin, Madison, Wisconsin.
Susan A
SA
Anderson
University of Wisconsin, Madison, Wisconsin.
David L
DL
DeMets
D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000368:Aged; D057911:Angiotensin Receptor Antagonists / Q000627:therapeutic use*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D058406:Cardiac Resynchronization Therapy / Q000379:methods*; D058409:Cardiac Resynchronization Therapy Devices; D002908:Chronic Disease; D017147:Defibrillators, Implantable; D004232:Diuretics / Q000627:therapeutic use*; D005260:Female; D006333:Heart Failure / Q000503:physiopathology / Q000628:therapy*; D006760:Hospitalization / Q000706:statistics & numerical data*; D006801:Humans; D008297:Male; D008875:Middle Aged; D000451:Mineralocorticoid Receptor Antagonists / Q000627:therapeutic use; D009026:Mortality; D016032:Randomized Controlled Trials as Topic; D013148:Spironolactone / Q000627:therapeutic use; D013318:Stroke Volume; D016896:Treatment Outcome
D000319:Adrenergic beta-Antagonists; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D004232:Diuretics; D000451:Mineralocorticoid Receptor Antagonists; D013148:Spironolactone
biventricular pacing; cardiac resynchronization therapy; chronic heart failure; implantable cardiac defibrillator; intraventricular conduction delays