New Study Shows Benefits of Coversyl (R) (Perindopril) in Elderly With Chronic Heart Failure (1)

BARCELONA, Spain, September 3 /PRNewswire/ --

-- Coversyl(R) in PEP-CHF Trial, is the First Agent to Demonstrate Clinical Benefits in Elderly Heart Failure Patients With Diastolic Dysfunction

The ACE inhibitor Coversyl(R) (perindopril) provides a number of clinical benefits to elderly people with chronic heart failure according to the results of a study presented at the World Congress of Cardiology today. The first of its kind in elderly patients with diastolic heart failure, the PEP-CHF (Perindopril in Elderly People with Chronic Heart Failure) study shows that Coversyl improved symptoms and exercise capacity and led to fewer hospitalisations for heart failure in the first year of treatment.(1)

Although this study lacked sufficient statistical power to show a long-term reduction in morbidity and mortality, "The results suggest that perindopril treatment is of benefit in this elderly population", points out lead study investigator Professor John Cleland, Department of Cardiology, University of Hull, UK. "This is a clinically important study as the prevalence of heart failure increases substantially with age. No other agent has been shown to be effective in relieving symptoms, improving functional capacity or reducing morbidity in older patients with heart failure and diastolic dysfunction."

Estimates of the prevalence of symptomatic heart failure in the general European population range from 0.4 to 2% and the prevalence of heart failure increases rapidly with age.(2) Chronic heart failure may be associated with diastolic dysfunction, an inability to fill the ventricle of the heart to its normal volume. Diastolic dysfunction is most often associated with older age, hypertension, coronary artery disease (CAD), atrial fibrillation and diabetes. Compared to patients with heart failure and a low left ventricular ejection fraction, diastolic heart failure patients are usually older, more often women, more commonly hypertensive but less likely to have a history of myocardial infarction.(3)

The multicentre, double-blind, randomised, parallel group, placebo controlled study involved 850 patients of 70 years or older (mean age 76). PEP-CHF set out to compare the effects of Coversyl and placebo on morbidity and mortality in older patients with clinical evidence of heart failure secondary to left ventricular diastolic dysfunction. The primary endpoint of the study was a composite of mortality due to any cause and unplanned heart failure-related hospitalisation with a minimum follow-up of one year. The median follow up of patients was 2.1 years.

Initiation of Coversyl was well tolerated in this elderly population. By one year, 65 patients (15.3%) assigned to placebo and 46 (10.8%) assigned to Coversyl experienced a primary outcome event (p=0.055). At the end of follow-up, there was no statistical significance between the two groups, but nearly half of these elderly patients had stopped their study medication (placebo or Coversyl) most of whom went on to receive open label ACE inhibitors. Despite the high rate of cross-over, patients assigned to Coversyl spent a median of 5 fewer days in hospital for any reason (p=0.1600) and 3 fewer for cardiovascular reasons (p=0.0557).

During the first year of follow-up, 53 patients (12.4%) assigned to placebo, but only 34 (8%) of patients receiving Coversyl had an unplanned hospitalisation for heart failure (p=0.033). At one year, patients receiving active treatment were more likely to have improved New York Heart Association (NYHA) functional class (p<0.03). In addition, patients given Coversyl had a greater increase in 6-minute corridor walk distance at one year (p=0.02). This is the first substantial trial to show that a treatment, Coversyl, can improve symptoms and functional capacity in patients with diastolic heart failure.

Coversyl is the first agent to demonstrate clinical benefits in this population. In CHARM-Preserved, which evaluated angiotensin receptor blocker (ARB) efficacy in a population of heart failure patients with preserved left ventricular ejection fraction (LVEF), candesartan did not achieve statistical significance in the primary end-point: cardiovascular mortality and unplanned hospitalisation for heart failure (p=0.118). Interestingly, this endpoint was significantly reduced by Coversyl in PEP-CHF over 1 year (p=0.018).

PEP-CHF is the fifth large-scale trial successfully conducted with Coversyl, providing an impressive demonstration of efficacy all along the cardiovascular disease continuum:

-- 2001: PROGRESS in post-stroke patients [+/- indapamide](n= 6 000): 28% reduction of secondary stroke(4)

-- 2003: EUROPA in stable coronary artery disease patients (n=12 000): 20% reduction of combined endpoints death / myocardial infarction / hospitalisation for heart failure(5)

-- 2005: ASCOT-BPLA in hypertensive patients without cardiac disease [in association with amlodipine] (n=20 000): 11% reduction of total mortality, 24% reduction of cardiovascular mortality, 23% reduction of stroke, 30% reduction of new onset of diabetes (6)

-- 2005: PREAMI in post- myocardial infarction patients (n=1 200): 22% reduction of death / heart failure / cardiac remodelling(7)

-- 2006: PEP-CHF in heart failure patients with preserved left ventricular ejection faction (n=850): 31% reduction of death / unplanned hospitalisation for heart failure at 1 year(1)

Coversyl

Coversyl (perindopril) is a long-acting ACE inhibitor with a high affinity for tissue ACE. It was discovered and developed by Servier and is licensed worldwide for hypertension and heart failure at the dosages of 4 to 8 mg. In the EU, it is also indicated in stable coronary artery disease to reduce the risk of cardiac events in patients with a history of MI and/or revascularisation. In the US, the FDA has approved a label extension for perindopril for a similar indication.

Perindopril is marketed in 118 countries under the trade names COVERSYL(R), COVEREX(R), ACERTIL(R), ARMIX(R), PRESTARIUM(R), PREXANIL(R), PREXUM(R), COVERENE(R), COVERSUM(R), PROCAPTAN(R) and marketed by Solvay Pharmaceutical and CV Therapeutics under the trade name of ACEON(R) in the US.

References

1. ESC hotline session: European Society of Cardiology, Sunday 3rd September 2006

2. Swedberg, K et al. European Society of Cardiology Guidelines: Guidelines for the diagnosis and treatment of chronic heart failure 2005

3. Lenzen MJ, Scholte op Reimer WJM, Boersma E, Vantrimpont PJMJ, Follath F, Swedberg K et al. Differences between patients with a preserved and a depressed left ventricular function: a report from the EuroHeart Failure Survey. Eur Heart J 2004;25:1214-20

4. PROGRESS Collaborative Group. Randomised trial of a perindopril-based blood pressure lowering regimen among 6105 individuals with previous stroke or transient ischaemic attack. Lancet 2001; 358:1033-41

5. Fox KM; European trial on reduction of cardiac events with perindopril in stable coronary artery disease investigators. Efficacy of perindopril in reduction of cardiovascular events among patients with stable coronary artery diseased: randomised, double-blind, placebo-controlled, multicentre trial (the EUROPA study). Lancet 2003;362:782-8

6. Poulter, NR et al. Role of blood pressure and other variables in the differential cardiovascular event rates noted in the Anglo-Scandinavian Cardiac Outcomes Trial Blood Pressure Lowering Arm (ASCOT-BPLA). Lancet 2005; DOI:10.1016/S0140-6736(05) 67186-3

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