European Heart Journal Advance Access published online on September 8, 2006
European Heart Journal, doi:10.1093/eurheartj/ehl250
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1 Department of Cardiology, University of Hull, Castle Hill Hospital, Castle Road, Cottingham,Kingston upon Hull HU16 5JQ, UK
* To whom correspondence should be addressed. 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 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.
Received August 8, 2006
Revised August 27, 2006
Accepted August 29, 2006
Clinical research
The perindopril in elderly people with chronic heart failure (PEP-CHF) study
John GF Cleland 1 *, Michal Tendera 2, Jerzy Adamus 3, Nick Freemantle 4, Lech Polonski 5, and Jacqueline Taylor 6, on behalf of PEP-CHF Investigators
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
John GF Cleland, E-mail: j.g.cleland{at}hull.ac.uk
Abstract 
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.
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