European Heart Journal Advance Access originally published online on September 8, 2006
European Heart Journal
2006 27(19):2338-2345; doi:10.1093/eurheartj/ehl250
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The perindopril in elderly people with chronic heart failure (PEP-CHF) study
1 Department of Cardiology, University of Hull, Castle Hill Hospital, Castle Road, Cottingham,Kingston upon Hull HU16 5JQ, UK
2 Silesian School of Medicine, Katowice, Poland
3 Department of National Defence, Warsaw, Poland
4 University of Birmingham, Birmingham, UK
5 Silesian School of Medicine, Zabrze, Poland
6 Glasgow Royal Infirmary, Glasgow, Scotland
Received 8 August 2006; revised 27 August 2006; accepted 29 August 2006; online publish-ahead-of-print 8 September 2006.
* Corresponding author. Tel: +44 1482 624 084; fax: +44 1482 624 085. E-mail address: j.g.cleland{at}hull.ac.uk
See page 2257 for the editorial comment on this article (doi:10.1093/eurheartj/ehl249)
Aims Many patients who receive a diagnosis of heart failure have neither a low left ventricular (LV) ejection fraction nor valve disease. Few substantial randomized controlled trials have been conducted in this population, none has focussed on patients with evidence of diastolic dysfunction and none has shown clear benefit on symptoms, morbidity, or mortality.
Methods and results This was a randomized double-blind trial, comparing placebo with perindopril, 4 mg/day in patients aged 
70 years with a diagnosis of heart failure, treated with diuretics and an echocardiogram suggesting diastolic dysfunction and excluding substantial LV systolic dysfunction or valve disease. The primary endpoint was a composite of all-cause mortality and unplanned heart failure related hospitalization with a minimum follow-up of 1 year. A total of 850 patients were randomized. Their mean age was 76 (SD 5) years and 55% were women. Median follow-up was 2.1 (IQR 1.5–2.8) years. Enrolment and event rates were lower than anticipated, reducing the power of the study to show a difference in the primary endpoint to 35%. Many patients withdrew from perindopril (28%) and placebo (26%) after 1 year and started taking open-label ACE-inhibitors. Overall, 107 patients assigned to placebo and 100 assigned to perindopril reached the primary endpoint (HR 0.919: 95% CI 0.700–1.208; P=0.545). By 1 year, reductions in the primary outcome (HR 0.692: 95% CI 0.474–1.010; P=0.055) and hospitalization for heart failure (HR 0.628: 95% CI 0.408–0.966; P=0.033) were observed and functional class (P<0.030) and 6-min corridor walk distance (P=0.011) had improved in those assigned to perindopril.
Conclusion Uncertainty remains about the effects of perindopril on long-term morbidity and mortality in this clinical setting since this study had insufficient power for its primary endpoint. However, improved symptoms and exercise capacity and fewer hospitalizations for heart failure in the first year were observed on perindopril, during which most patients were on assigned therapy, suggesting that it may be of benefit in this patient population.
Key Words: ACE-inhibitors • Diastolic heart failure • Randomized trial • Morbidity and mortality
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