Kwame O Akosah MD

1
ACE in hypotensive HF patients

• Kwame O Akosah MD
• Associate Clinical Professor of Medicine
• University of Wisconsin - Madison
• Director, Heart Failure Clinic
• Gundersen Lutheran Medical Center
• La Crosse, WI

2
Congestive heart failure

• Congestive heart failure (CHF) is a major public
  health challenge
  
• Morbidity and mortality are substantial (1997
  mortality 45,419)
  
• Prevalence is increasing (4,600,000)
• people are living longer
• CHF is more prevalent in the elderly population

American Heart Association. 2000 Heart and Stroke
Statistical Update, 1999
3
Heart failure therapy
ACE inhibitors

• ACE (angiotensin converting enzyme) inhibitors
  are the mainstay of heart failure therapy
  
• several large trials have proven the benefits of
  ACE inhibitors in the treatment of CHF
  
• unfortunately, most patients do not receive ACE
  inhibitors those who do often get inadequate
  doses
  
• no multicenter trials have included patients with
  symptomatic hypotension

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The CHF clinic

• The heart failure clinic was established in April
  1999 as an outpatient service for patients with
  severe heart failure
  
• A significant number of patients referred to the
  clinic had symptomatic hypotension along with
  severe heart failure

5
The CHF clinic
Study objectives

• To determine efficacy, safety, and tolerability
  of ACE inhibitors in heart failure patients with
  symptomatic hypotension
  
• To examine the effect of ACE inhibitors on
  symptoms of hypotension and functional status
  
• To study the hemodynamic responses to ACE
  inhibitors as measured by blood pressure (BP) at
  optimal and maximal doses of ACE inhibitors

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The CHF clinic
Study population

• 104 of the 220 patients seen in the clinic have
  been discharged
  
• 27 of these meet the criteria for symptomatic
  hypotension
  
• 20 were men
• mean age was 64 ? 10 years (4585)
• 7 (26) could not tolerate ACE inhibitors and
  were prescribed angiotensin receptor blockers
  (ARBs)
  
• all 20 on ACE inhibitors were optimized and 15
  (75) were maximized at their last visit

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The CHF clinic
Assessment

• Inclusion criteria
• those who had been discharged from the clinic
• those with systolic BP ? 100 mm Hg and symptoms
  of hypotension at their first visit
  
• Assessment
• BP was assessed at presentation, on optimal and
  maximal doses of ACE inhibitor, at discharge, and
  at most recent clinic visit
  
• maximal dose 40 mg lisinopril or equivalent
• optimal dose 20 and equivalent
  
• New York Heart Association (NYHA) class was
  assessed on presentation and at discharge

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The CHF clinic
BP with ACE inhibitor therapy
112 ? 15mm Hg
103 ? 11mm Hg
101 ? 13mm Hg
120
86 ? 12mm Hg
100
80
SBP (mm Hg)
60
40
20
0
baseline
optimaldose
maximaldose
6-monthfollow-up
p 0.003 from baseline p 0.004 from baseline

p 0.002 from baseline
Akosah KO, et al. October 25, 2000
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The CHF clinic
Treatment and functional class

• All patients showed improvement in symptoms of
  hypotension
  
• The mean NYHA functional class at baseline was
  3.5 ? 0.6
  
• At follow-up, the mean NYHA functional class was
  2.5 ? 0.6
  
• None of the patients were in NYHA class IV by the
  end of the study

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The CHF clinic
Early improvement in hypotension

• The hemodynamic effects of the stresses
  associated with heart failure may be more
  deleterious than the hypotensive effects of ACE
  inhibitors
• An analogy would be giving epinephrine to someone
  with asthma
  
• epinephrine would be expected to increase the
  heart rate further
  
• but because epinephrine relieves the stress of
  breathing, the heart rate actually goes down

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The CHF clinic
Late improvement in hypotension

• The late improvement is probably related to the
  effect of ACE inhibitors on reverse remodeling of
  the heart
  
• As the heart remodeling is attenuated and perhaps
  reversed, shape, volume, and BP of the heart also
  improve

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The CHF clinic
Monitoring and titrating

• All the people who had symptomatic hypotension
  were started on a very low dose of ACE inhibitor
  (eg, 2.5 mg of lisinopril)
  
• Dose was titrated up very slowly
• Patients were seen as frequently as needed
  sometimes every day

13
The CHF clinic
Discharge to care of family physician

• Records and instructions were sent to the family
  physician at discharge
  
• Patients received instructions on specific issues
  (eg, the clinic should be contacted before a
  physician stops or changes any of their
  medications)
• The clinic makes follow-up calls to the primary
  care physician to monitor the progress of
  patients
  
• Communication with primary care physicians is
  very important

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The CHF clinic
ACE intolerance

• Some patients develop an intolerance to ACE
  inhibitors
  
• patients who develop allergic reactions
• patients who continue to have symptomatic
  hypotension
  
• patients who develop angioedema
• patients who develop intolerant cough
• In this study, 7 people who were ACE intolerant
  were prescribed ARBs

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The CHF clinic
ACE inhibitors vs ARBs
Akosah KO, et al. Presented at the meeting of the
American College of Chest Physicians, October
25, 2000, San Fransico, CA
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The CHF clinic
Conclusions

• CHF patients with symptomatic hypotension can be
  successfully treated with ACE inhibitors
  
• Hypotension is not a legitimate reason to deny
  CHF patients life-saving medications such as ACE
  inhibitors
  
• Functional status improves with therapy in CHF
  patients
  
• With ARBs, improvements in BP are not
  significant however symptoms of hypotension do
  improve
  
• To try to duplicate these results in a wider
  groups of patients from various clinical
  practices, we are currently looking for other
  centers to collaborate in a larger study

17
HF and sudden death
The use of AICDs

• The use of automatic implantable cardioverter
  defibrillators (AICD) in heart failure patients
  is becoming more common
  
• Objective
• To evaluate the impact of AICD in patients
  enrolled in the heart failure clinic
  
• Method
• A retrospective review of shocks in patients with
  an AICD device was conducted
  
• Data were analyzed for the number of shocks
  before enrollment and after optimization of
  medical management

Akosah KO, et al. Presented at the meeting of the
American College of Chest Physicians, October
25, 2000, San Fransico, CA
18
HF and sudden death
Results

• Of the first 100 consecutive patients enrolled in
  the clinic, 22 had an AICD
  
• Cardiac death occurred in 1 patient (fatal MI)
• Of the remaining 21, 6 patients (29) had 23
  shocks before enrollment in the clinic, 1 of
  which was inappropriate
  
• 2 shocks occurred after enrollment (90
  reduction)
  
• 1 shock was inappropriate and the other shock
  occurred within a week of enrollment
  
• No shocks occurred after medical therapy was
  optimized

Akosah KO, et al. Presented at the meeting of
theAmerican College of Chest Physicians, October
25, 2000, San Fransico, CA
19
HF and sudden death
Conclusions

• Results suggest that malignant arrhythmias are
  common in decompensated heart failure patients
  and that aggressive medical therapy may have
  incremental value in preventing sudden death in
  high-risk heart failure patients with an AICD
• Clinical implications
• Heart failure patients with an AICD will benefit
  from aggressive medical therapy

Akosah KO, et al. Presented at the meeting of
theAmerican College of Chest Physicians, October
25, 2000, San Fransico, CA