Psychiatric characteristics associated with long-term mortality among 361 patients having an acute coronary syndrome and major depression: seven-year follow-up of SADHART participants

Alexander H Glassman, J Thomas Bigger, Michael Gaffney
Archives of General Psychiatry 2009, 66 (9): 1022-9

CONTEXT: Major depressive disorder (MDD) after acute coronary syndrome (ACS) is associated with an increased mortality rate. We observed the participants of the Sertraline Antidepressant Heart Attack Randomized Trial (SADHART) to establish features of MDD associated with long-term mortality.

OBJECTIVES: To determine whether the following variables were associated with long-term mortality: baseline depression severity, previous MDD episodes, onset of MDD before or after the ACS event, 6 months of sertraline hydrochloride therapy, and mood improvement independent of treatment.

DESIGN: SADHART was a double-blind, placebo-controlled, randomized trial comparing the safety and antidepressant efficacy of sertraline vs placebo in 369 patients with ACS who met criteria for MDD. The trial was completed in June 2000, and follow-up for vital status was completed in September 2007.

SETTING: Academic research.


MAIN OUTCOME MEASURES: Vital status was determined in 361 participants (97.8%) during a median follow-up of 6.7 years.

RESULTS: During the study, 75 participants (20.9%) died. Neither previous episodes of MDD, nor onset before or after the index ACS, nor an initial 6 months of sertraline treatment was associated with long-term mortality. Cox proportional hazards regression models showed that baseline MDD severity (hazard ratio, 2.30; 95% confidence interval, 1.28-4.14; P < .006) and failure of MDD to improve substantially during treatment with either sertraline or placebo (hazard ratio, 2.39; 95% confidence interval, 1.39-2.44; P < .001) were strongly and independently associated with long-term mortality. Marked improvement in depression (Clinical Global Impression-Improvement subscale score of 1) was associated with improved adherence to study medication.

CONCLUSIONS: Severity of MDD measured within a few weeks of hospitalization for ACS or failure of MDD to improve during the 6 months following ACS predicted more than a doubling of mortality over 6.7 years of follow-up. Because persistent depression increases mortality and decreases medication adherence, physicians need to aggressively treat depression and be diligent in promoting adherence to guideline cardiovascular drug therapy.

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