CPP Past Year Exam 2007

1. In own words, describe the aim of this study and explain why
the study was undertaken.
Most of the studies had been investigated the clinical outcome of
ACE inhibitors, beta blocker and ARB in patients who had low LVEF.
Only 1 trial using digoxin had been targeted patients with CHF and
LVEF higher than 40%. Hence, a lot of the current guidelines for HF
treatment did not take patients with LVEF higher than 40% into
account or basically just extrapolate from the results from patients
with low LVEF (<40%). It is remain unknown whether this
extrapolate is justified or not. Besides that, for patient who had high
risk of cardiovascular disease associated with preserved LVEF and
no CHF, ACE inhibitor seems to decrease the rate of mortality and
morbidity. Therefore, the aim of this study the potential advantages
of ARB (cadesartan) towards patients with CHF and preserved LVEF.
This study was done by evaluating the effects of candesartan on the
rate of admission to hospital and mortality rate in patients with
worsening CHF.

2. Pharmacology of candesartan and compare it with the

pharmacology of ACE inhibitors. What additional benefits
might you expect if candesartan is given to a patient who is
already taking an Ace inhibitor.
3. Describe the study protocol in your own words
First, the patients who met the following requirements to participate
in this study was selected.
1. 18 years old and above
2. had New York Heart Association functional class 2-4 of at least 4
weeksduration
3. admitted into the hospital before due to cardiac problem.
4. Had LVEF higher than 40%.
GP were allowed to prescirbe all treatments except ARB.
The use of ACE inhibitor is optional however appropriate in
patients after the trials results of Heart outcomes prevention
evaulaton were published.
Besides that, this study was being approved by ethics committe. Of
course the patients were given written inform consent.
Next, the patients were then randomly assigned to either to
matched placebo or candesartan group. This was done in double
blinded way. Then, the patient was given either 4mg or 8mg once
daily as starting dose. The dose was titrated up (doubled the dose)
in every 2 weeks as tolerated. Titration of dose was done according
to force titration protocol. Blood pressure, serum creatinine and
potassium monitoring was also done by means of force titration
protocol. The patient were reviewed at the weeks of 2,4,6 and at 6
months, then every 4 months until the trial end time. However, in
patients who enrolled in North America, regular lab assesment was
done at baseline, then every 6 weeks and annually for safety
purposes.

4. Explain what is meant by pre specified composite and primary

outcome. Why have both of these been analysed?
Pre specified composite (outcome) is mean by a clinical event that
is defined before the start of clinical trials as the main factor for
comparing the active drugs with placebo in statistical analysis of
the drug.

5. What is relative risk reduction and an alpha level of 0.05

mean under statistical methods.
Relative risk reduction is decrease in incidence of active group when
compared with control group. It is calculated by ARC-ART/ARC. For
example:
Alpha level of 0.05 means that a statistically signifcant difference is
defind as having a proability of 0.95 there is a <5% chance of
classifying a difference between placebo and active drug as
significant when no real difference exist.

6. Describe in your own words, and with reference to Table 2 and

3 and Figure 2 the results for the primary and secondary
outcome measurements.
Table 2 shown the primary and secondary outcomes of this study.
Primary outcome: Cardiovascular death or hospital admission for
CHF.
It was shown that the relative risk reduction was 11% with the
95% CI (0.74 -1.0) and p value = 0.051. p value =0.051 which is
more than 0.051. This means that there was no statistically
significance between the control group and placebo group in
cardiovascular death or hospital admission for CHF.
Secondary outcome: Cardiovascular death, hospital admission for
MI, CHF,stroke or coronary revascularisation procedure.
Table 3 shown numbers of hospital admission for worsening heart
failure. It was shown that the total number hospital admission due
to CHF was significantly reduce in patients treated with cadestaran
if compared to the placebo group. (p value= 0.014, 402 vs 566
people). The number of people who were admitted into the hospital
due to CHF was again significantly reduce in cadersatan group
when compared with placebo group. (p = 0.017, 230 vs 279). There
was consistently decrease of
Figure 2 shown the time to cardiovascular death or hospital
admission for CHF.

7. Limitation and how can improved.