Depression and Myocardial Infarction: Findings of the SADHART Group

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Depression and Myocardial Infarction Findings
of the SADHART Group

• June 23, 2004
• Tracy Ann Rydel, MD

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Influence of Depression and Effect of Treatment
with Sertraline on Quality of Life after
Hospitalization for Acute Coronary Syndrome

• American Journal of Cardiology.
• Dec 2003. 92 1271-1276.

3
The SADHART Group

• SADHART Sertraline Antidepressant Heart Attack
  Randomized Trial
• Trial conducted in 40 outpatient cardiology
  centers and psychiatry clinics in U.S., Canada,
  Australia, and Europe
• Study financially supported by Pfizer

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Relevance of SADHART

• Depression as a risk factor for mortality
  post-MI1
• Older antidepressants potentially cardiotoxic
  and/or proarrythmic
• SSRIs not previously established as safe or
  beneficial post-MI

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The Groundwork

• Initial study entitled Sertraline Treatment of
  Major Depression in Patients with Acute MI or
  Unstable Angina.
• Presented in JAMA, August 2002. 288 (6)
  701-710.
• Established safety of SSRIs in patients with
  recent MI or unstable angina

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METHODS The Subjects

• 369 patients
• 74 post-acute MI 26 unstable angina
• 100 with current episode of MDD, based on DSM-IV
  criteria with Beck Depression Inventory Score gt
  10
• 2 groups 1. Intent-to-Treat (Total)
• 2. Recurrent Depression

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METHODS The 2 Subgroups
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METHODS Why 2 groups?

• Intent-to-treat vs. Recurrent Depression
  subgroup
• Definition
• Determined a priori
• Overlap of symptomatology between MDD and
  physical illness
• Most post-MI depression considered similar to an
  adjustment disorder
• Recurrent depression is associated with
  persistent depression in the year following MI

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METHODS The Subjects

• Exclusion criteria
• Cardiovascular
• -uncontrolled HTN
• -cardiac surgery candidates (next 6 months)
• -MI or UA less than 3 months post-CABG
• -bradycardia (resting HR lt 40)
• Other medical
• -persistent clinically significant laboratory
  abnormalities
• -significant renal or hepatic disease or other
  noncardiac disease

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METHODS The Subjects (cont.)

• Exclusion criteria (cont.)
• Psychiatric
• -alcohol or substance abuse in past 6 mo
• -psychotic symptoms, h/o psychosis, bipolar
  d/o, organic brain syndrome, dementia
• -significant suicide risk

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METHODS The Treatment

• Patients randomized to receive 24 weeks of
  double-blind Rx Sertraline or placebo
• Patients in Sertraline group received 50 mg daily
  for first 6 weeks titration to 200 mg permitted
• Compliance checked using pill counts

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METHODS Outcome Measures

• 2 Effect-on-Depression measures
• HAM-D
• (Hamilton Rating
• Scale for Depression)
• CGI-I score
• (Clinical Global Impression, Improvement Scale)

• 2 Quality of Life measures
• Q-LES-Q
• (Quality of Life Enjoyment and Satisfaction
  Scale)
• SF-36
• (Medical Outcomes Study Short Form 36)

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RESULTS The Statistics

• 2 patient groups analyzed
• 2 outcome domains investigated
• 2 scales within each domain evaluated
• Mixed-model repeated measures analysis of
  covariance utilized to assess changes in scores
  over the treatment period

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RESULTS Depression Measures

• The HAM-D scale
• Significantly greater improvement seen with
  Sertraline in the Recurrent Depression subgroup
  (p0.002) as compared to placebo
• No significant difference demonstrated in the
  total randomized group

• The CGI score
• Sertraline had significant effect in both the
  Recurrent Depression subgroup (plt0.001) AND in
  the total randomized group (plt0.01) as compared
  to placebo

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RESULTS Quality of Life Measures

• Q-LES-Q
• Significant effect of Sertraline relative to
  placebo shown in Recurrent Depression subgroup
  (p0.037)

• SF-36
• Sertraline showed clinically significant
  improvement over placebo in the Mental Component
  of the SF-36 in the Recurrent Depression subgroup
  (p0.010)

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Efficacy in Post-ACS Depression

• Week 24
• Responder
• Rates for
• Sertraline vs.
• Placebo
• The CGI-I
• p lt 0.01 p lt 0.003

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Improvement in SF-36 scores

• Significant
• difference
• shown in
• mental
• component
• of recurrent
• group
• (p0.010)

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SF-36 subscale scores Sertraline vs. placebo in
the recurrent group

• p lt 0.05 p lt 0.001 p lt 0.10

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DISCUSSION Indications for Clinical Practice

• Results of study especially relevant for
  Recurrent Depression subgroup
• Findings to be considered exploratory given
  small sample size
• Depression as strongest predictor of baseline
  quality-of-life impairment following acute
  coronary syndrome5

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DISCUSSION Limitations of the Current Study

• Conclusions cannot be generalized to all
  patients
• Exclusion of pts with renal or hepatic
  dysfunction
• Exclusion of pts with psychiatric comorbidities
• Exclusion of pts with alcohol or substance abuse
  in past 6 months

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DISCUSSION Limitations of the Current Study
(cont.)

• Sertraline as only SSRI tested
• Drug not administered until 1 month post-MI
• No discussion of absence of significant effects
  on physical functioning (SF-36)
• Non-pharmacologic measures not explored4

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DISCUSSION Areas for Further Investigation

• Repeat trial with larger cohort similar to
  Recurrent Depression subgroup needed
• Study examining differences in long-term post-MI
  mortality between SSRI and placebo
• Depression or MI which came first? Or, how are
  these factors interrelated?

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THANK YOU!

• Dr. David Thom
• Julie Haugen

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REFERENCES

• 1 Bush DE, et al. Even minimal symptoms of
  depression increase mortality risk after acute
  myocardial infarction. American Journal of
  Cardiology. 2001. 88 337-41.
• 2 Glassman AH, et al. Sertraline Treatment of
  Major Depression in Patients with Acute MI or
  Unstable Angina JAMA, August 2002. 288 (6)
  701-10.
• 3 Glassman AH, et al. Influence of Depression
  and Effect of Treatment with Sertraline on
  Quality of Life after Hospitalization for Acute
  Coronary Syndrome. American Journal of
  Cardiology.Dec 2003. 92 1271-6.
• 4 Lavie CJ and Milani RV. Cardiac
  rehabilitation and depression. Letter in
  American Journal of Cardiology. 2004. 93 1080.
• 5 Rumsfeld JS, et al. Predictors of quality of
  life following acute coronary syndromes.
  American Journal of Cardiology. 2001. 88 781-4.

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