In their recent analysis of the causes of death that occurred in the course of the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) trial,1 the AFFIRM investigators speculate that a favorable effect of oral anticoagulants and/or an unfavorable effect of amiodarone could explain the higher noncardiovascular death rate—especially pulmonary and cancerrelated deaths—recorded among patients originally randomized to rhythm control (versus rate control). Cause-specific mortality was analyzed on an intention-to-treat basis.1 However, in view of the high crossover rates (21% of the population during the course of the study),2 we think that exposure times to each of the strategies and therapies need to be taken into account. To do this, a time-dependent, on-treatment analysis would be necessary, whereby patients are analyzed according to the actual therapy received, and adverse events or outcomes are attributed to the treatments actually applied.3 The necessity for this is stressed by the survival curves for noncardiovascular mortality, where excess mortality in the rhythm control arm began to emerge after 1 year of treatment.1 By that time, the crossover from rhythm to rate control was already substantial (rates of 16.7%, 27.3%, and 37.5% were recorded at 1, 3, and 5 years, respectively).2 In addition to evaluation of time-dependent covariates, a series of known potential determinants of pulmonary and cancer-related mortality (including environmental, lifestyle, and occupational factors) also require consideration. Such an analysis would allow a more reliable exploration of the possible relations between rhythm control and occurrence of pulmonary and cancer-related deaths.
Rhythm control and increased risk of noncardiovascular death in the atrial fibrillation follow-up investigation of rhythm management trial
MATTIOLI, STEFANOUltimo
Writing – Original Draft Preparation
2004
Abstract
In their recent analysis of the causes of death that occurred in the course of the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) trial,1 the AFFIRM investigators speculate that a favorable effect of oral anticoagulants and/or an unfavorable effect of amiodarone could explain the higher noncardiovascular death rate—especially pulmonary and cancerrelated deaths—recorded among patients originally randomized to rhythm control (versus rate control). Cause-specific mortality was analyzed on an intention-to-treat basis.1 However, in view of the high crossover rates (21% of the population during the course of the study),2 we think that exposure times to each of the strategies and therapies need to be taken into account. To do this, a time-dependent, on-treatment analysis would be necessary, whereby patients are analyzed according to the actual therapy received, and adverse events or outcomes are attributed to the treatments actually applied.3 The necessity for this is stressed by the survival curves for noncardiovascular mortality, where excess mortality in the rhythm control arm began to emerge after 1 year of treatment.1 By that time, the crossover from rhythm to rate control was already substantial (rates of 16.7%, 27.3%, and 37.5% were recorded at 1, 3, and 5 years, respectively).2 In addition to evaluation of time-dependent covariates, a series of known potential determinants of pulmonary and cancer-related mortality (including environmental, lifestyle, and occupational factors) also require consideration. Such an analysis would allow a more reliable exploration of the possible relations between rhythm control and occurrence of pulmonary and cancer-related deaths.I documenti in SFERA sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
