Transcript Dosage of enalapril for congestive heart failure in USA

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
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
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
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
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
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 (45–85)
 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
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 <40 mg lisinopril or
equivalent
New York Heart Association (NYHA) class was assessed
on presentation and at discharge
The CHF clinic
BP with ACE inhibitor therapy
SBP (mm Hg)
120
100
86  12
mm Hg
101  13
mm Hg*
103  11
mm Hg†
112  15
mm Hg‡
maximal
dose
6-month
follow-up
80
60
40
20
0
baseline
*p = 0.003 from baseline
†p = 0.004 from baseline
‡p = 0.002 from baseline
optimal
dose
Akosah KO, et al. October 25, 2000
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
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
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
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
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
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
The CHF clinic
ACE inhibitors vs ARBs
SBP (mm Hg)
At
At
maximal
baseline
dose
At 6month
follow-up
Change
from
baseline to
6 months
p
ACE
inhibitors
86
103
112
26
0.002
ARBs
93
NA
95
2
ns
Akosah KO, et al. Presented at the meeting of the
American College of Chest Physicians, October 25, 2000, San Fransico, CA
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
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
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 the
American College of Chest Physicians, October 25, 2000, San Fransico, CA
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 the
American College of Chest Physicians, October 25, 2000, San Fransico, CA