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Sertraline Treatment of Major Depression in Patients With Acute MI or Unstable Angina - SADHART
Description:
This trial assessed the safety and efficacy of sertraline, a selective serotonin reuptake inhibitor (SSRI) antidepressant in the treatment of major depressive disorders in post-MI and unstable angina patients.
Study Design
Study Design:
Patients Enrolled: 369
Secondary Endpoints:
effect on depression mesasure by the HAM-D and CGI-I scales, and effects on other cardiovascular endpoints with an emphasis on a clincial composite, heart rate variability, and corrected QT interval.
Drug/Procedures Used:
This is a randomized double blind placebo controlled trial of 24 weeks of sertraline, titrated from 50 to 200 mg, in 369 men and women discharged within 30 days of an acute MI or unstable angina. All patients had at least 2 weeks of depression by Diagnostic Statistical Manual (DSM) IV criteria and the Beck Depression Inventory (BDI). Those with depression limited to the acute event were analyzed separately. The primary endpoint was change in LVEF by MUGA, and secondary measures included effect on depression measured by the Hamilton Depression Score (HAM-D) and the Clinical Global Depression Improvement scale (CGI-I), and effects on other cardiovascular endpoints with an emphasis on a clinical composite, heart rate variability, and corrected QT interval (QTc).
Principal Findings:
369 of the 3,355 patients who underwent the psychological evaluation and BDI screening met eligibility criteria and were randomized, 186 to sertraline. There was no difference between groups with respect to the following: depression score, prior use of anti-depressants (35%), frequency of 2 prior episodes with a HAM-D score >18, the index event classified as an MI (80%), LVEF (53%), Killip class I (93%), and previous MI other than the index event (42%). Average age was 57 years, 37% were women, 28% current smokers, 31% diabetics, and BMI averaged >28 kg/m2. Use of concomitant cardiovascular medications was similar between groups with 91% treated with ASA, 85% with statins, 80% with beta blockers, and 55% with ACE inhibitors. Sertraline was not associated with any difference in the LVEF, 24hour Holter PVC's, PVC runs, R-R interval variability, or frequency of QTc greater than 450ms. There was no significant difference in deaths, MI, CHF, stroke, angina, or their composite. Major and minor CV symptoms or events occurred in 52.7% on sertraline and 59% on placebo. Sertraline was an effective antidepressant as measured by the CGI-I score (67% vs 53% for placebo), and was particularly effective in those with recurrent depression and high HAM-D scores (78% vs. 45%, p=0.001).
Interpretation:
Among patients with a recent MI or unstable angina, Sertraline is a safe and effective treatment for recurrent depression. In this small sutdy, there was no association with improved cardiovascular outcomes. Clinician's should have a high index of suspicion and should routinely assess for symptoms of depression among patients with CAD. Over 20% of patients with acute coronary events have depression unrelated to the event, and depression is associated with a 3-4 fold risk of subsequent CV morbidity and mortality in CAD. SSRI's are safe and reasonably effective based upon this relatively small study. About 4000 subjects will be needed to determine whether SSRI's have an effect on CV endpoints. It is unclear if a potential benefit of SSRIs would be mediated via sertonin, a reduction in anxiety and sympathetic drive or a reduction in social isolation.
References:
Glassman AH, O'Connor CM, Califf RM, et al for the Sertraline Antidepressant Heart Attack Randomized Trial (SADHART) Group. Sertraline Treatment of Major Depression in Patients With Acute MI or Unstable Angina. JAMA 2002;288:701-09.
Keywords: Stroke, Depressive Disorder, Major, Serotonin Uptake Inhibitors, Polyvinyl Chloride, Social Isolation, Coronary Disease, Heart Rate, Sertraline, Body Mass Index, Diabetes Mellitus
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