Alternative endpoints for mortality in studies of patients with atrial fibrillation: the AFFIRM study experience.
OBJECTIVE
The purpose of this study was to examine possible alternatives for death, particularly hospitalization for cardiovascular reasons (CV hospitalization), as an endpoint in studies of atrial fibrillation (AF) using the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) database.


BACKGROUND
AF is associated with increased mortality, but large numbers of patients are needed to demonstrate even a moderate effect of a therapy on mortality.


METHODS
AFFIRM studied 4,060 patients with AF, randomized to either rate-control or rhythm-control strategy with death as the primary endpoint.


RESULTS
Only CV hospitalization occurred more frequently than death. Like death, CV hospitalization was more frequent in the rhythm-control arm (46% vs 36%, P < .001) overall but not in a cohort that attempted to exclude those CV hospitalizations possibly related to treatment strategy (e.g., cardioversion, 24% vs 27%). In either model there was no interaction of CV hospitalization (analyzed as a time-dependent covariate) with treatment arm (P = .18 and P = .21, respectively). CV hospitalization was highly predictive of death in both treatment arms (P < .001) in either model, but after this event, there was no difference in time to death. A composite endpoint of CV hospitalization combined with death might increase power and reduce the size of trials of therapy for AF in such patients.


CONCLUSIONS
In patients with AF such as those in the AFFIRM study, CV hospitalization has many attributes of a surrogate for mortality. More research on CV hospitalization, alone or as part of a composite endpoint, is warranted.
Wyse
D George
DG
Libin Cardiovascular Institute of Alberta, University of Calgary, Canada.
Slee
April
A
Epstein
Andrew E
AE
Gersh
Bernard J
BJ
Rocco
Thomas
T
Vidaillet
Humberto
H
Volgman
Annabelle
A
Weiss
Robert
R
Shemanski
Lynn
L
Greene
H Leon
HL
D000368:Aged; D000889:Anti-Arrhythmia Agents / Q000627:therapeutic use; D001281:Atrial Fibrillation / Q000401:mortality* / Q000628:therapy; D003131:Combined Modality Therapy; D004554:Electric Countershock; D023381:Endpoint Determination; D005260:Female; D006470:Hemorrhage / Q000453:epidemiology; D006760:Hospitalization / Q000706:statistics & numerical data*; D006801:Humans; D008297:Male; D009203:Myocardial Infarction / Q000453:epidemiology; D016032:Randomized Controlled Trials as Topic; D012189:Retrospective Studies; D020521:Stroke / Q000453:epidemiology; D014481:United States / Q000453:epidemiology
D000889:Anti-Arrhythmia Agents