Safety and efficacy of rennin-angiotensin system
inhibitors in heart failure with preserved ejection
International Journal of Collaborative Research on
Internal Medicine & Public Health, 2011 - Vol.
Author(s): Mukesh Singh, Tejaskumar Shah,
Sasikanth Adigopula, Sandeep Khosla, Rohit Arora, Evyan
Cardiology, Chicago Medical School, United States
Approximately half of the patients with chronic heart
failure have preserved left ventricular systolic
function. The trials of rennin-angiotensin system
inhibitors (RASIs) in this population have yielded mixed
results. We performed a meta-analysis of these trials to
evaluate the safety and efficacy of RASIs in heart
failure with preserved ejection fraction patients.
A total of 8425 patients from six prospective randomized
controlled trials were analyzed. The end points
extracted were total mortality, cardiovascular
mortality, hospitalization for heart failure, worsening
of heart failure, worsening of renal failure,
hyperkalemia, hypotension, six minute walk test, quality
of life score. RASIs evaluated were perindopril,
enalapril, ramipril, valsartan, candesartan and
irbesartan. Combined odds ratios (OR) across all the
studies and 95% confidence intervals (CI) were computed.
A two-sided alpha error <0.05 was considered to be
statistically significant. All studies were homogeneous
for outcomes studied, so fixed effect model was used for
this meta- analysis.
Both groups share similar baseline characteristics.
There was significant reduction in worsening of heart
failure events [OR: 1.16, CI: 1.03-1.31; p<0.05] with
RASIs compared to placebo group. This was associated
with a tendency toward reduced hospitalizations due to
heart failure [OR: 1.11, CI: 0.99-1.24; p=0.052] but it
could not achieve statistical significance. RASIs also
failed to show any benefit in total mortality [OR: 1.07,
CI: 0.96-1.19; p=0.19] or cardiovascular mortality [OR:
1.01, CI: 0.89-1.15; p= 0.84] [Figure 1]. However,
treatment with RASI lead to significant improvement in
six minute walking distance [p<0.05] and quality of life
score in RASIs group [p=0.002] [Figure 1]. Safety
analysis, as expected, revealed significantly more
hyperkalemic events [OR: 0.53, CI: 0.29-0.95; p<0.05]
and worsening of renal failure [OR: 0.65, CI: 0.50-0.85;
p<0.05] in RASI group as compared to placebo group.
RASIs treatment in heart failure with preserve ejection
fraction patients showed significant improvement in six
minute walking distance, quality of life and significant
reduction in worsening heart failure events but failed
to reduce total and cardiovascular mortality.
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