Discussant: Dickstein, K.
The results of the PEP-CHF (The Perindopril in Elderly People with Chronic Heart Failure) study were presented by Professor John Cleland (Kingston-upon-Hull, GB) at Hot Line 1 on Sunday, 3 September.
The trial randomised 852 patients to either placebo or perindopril (4 mg). The population by design was older than that in most other heart failure studies with an average age of 75 years. In that this trial targeted patients with preserved ejection fraction, the demographics included 56% women, 79% patients with previous hypertension and the mean ejection fraction was 65%. The follow-up period was 26 months and the primary end point was all-cause death and heart failure hospitalisation.
The result of the primary end point (207 events) was a relative risk reduction of 8% in favour of perindopril which was not significant (HR 0.92; 95% CI 0.70 to 1.21; p=0.545). Although this is disappointing, major methodological limitations must be recognised in order to permit appropriate interpretation of the data (see figures). Importantly, at one year of follow-up there was a 31% relative risk reduction in the primary end point (p=0.055) and a 37% relative risk reduction in heart failure hospitalisation (p=0.033) in favour of perindopril.
It must be emphasised that although the trial was designed for one year recruitment and one year follow-up, the study was prolonged due to slow recruitment and a considerably lower event rate than originally expected. Unfortunately, this lead to a striking discontinuation rate of 38% at 18 months with ~90% of patients both on placebo and perindopril being placed on open ACE inhibitor treatment. This lead to a substantial loss of power. It is likely that this essential fact explains the course of the primary end point during the follow-up period and the loss of the effect observed at one year. This point can be readily observed from the form of the Kaplan-Meier curve for the primary end point. Clearly, there may also be alternative explanations for the loss of effect over time.
It should also be emphasised that other important measures of clinical status were strongly supportive of a positive effect of perindopril. These results are certainly consistent with the results in the CHARM Preserved arm in a similar but younger population treated over a follow-up of 37 months, which demonstrated a trend in favour of candesartan.
Neither of these trials provides adequate evidence for recommending the use of these agents in this population. However, taken together the results appear to support a role for inhibition of the renin-angiotensin system in patients with heart failure and preserved systolic function. We must be appropriately conservative in interpreting these results.
Most trialists and clinicians will be encouraged by the data and will eagerly await the results of the next major trial in a similar patient population, I-PRESERVE, which has randomised 4128 patients to placebo or irbesartan and should report next year.
[Slide Presentation Available]