Dallas, Texas, November 14 (ots/PRNewswire) -
- CAFÉ Study Shows Central Aortic Pulse Pressure Important
Determinant of Cardiovascular Outcomes
A new sub-study of the Anglo-Scandinavian Cardiac Outcomes Trial
(ASCOT)(1), presented during a late breaking clinical trial session
of the American Heart Association (AHA) meeting gave an explanation
for the amlodipine / Coversyl (perindopril) benefits in terms of
total mortality, cardiovascular mortality, stroke, and cardiovascular
events in comparison with the beta-blocker + diuretic combination.
The CAFÉ (Conduit Artery Function Evaluation) study is the largest
ever prospective evaluation of the effects of cardiovascular drugs on
derived central aortic pressures and hemodynamics. It found that
blood pressure (BP)-lowering drugs can have substantially different
effects on central aortic pressures and hemodynamics, despite a
similar impact on brachial (upper arm) BP. This demonstrates that
central pulse pressure appears to be an important determinant of
clinical outcomes. It provides a new plausible explanation for the
improved clinical outcomes seen in patients treated with the
amlodipine / perindopril combination.
"This study demonstrates for the first time in a large clinical
outcomes trial that BP-lowering drugs have profoundly different
effects on central aortic pressures and hemodynamics, despite a
similar impact on brachial (arm) blood pressure," said Bryan
Williams, MD, Professor of Medicine in the Department of
Cardiovascular Sciences at the University of Leicester in the UK.
"The results of this study are clear-cut, dramatic and potentially
very important. It may also explain why certain types of hypertension
treatment might be more effective than others."
Williams is the principal investigator for the Differential
Impact--Principal Results of the Conduit Artery Function Evaluation
(CAFE) study in ASCOT.
Brachial BP measurements are routinely used to monitor the
efficacy of BP-lowering treatments. Different BP-lowering drugs could
have differing effects on central aortic pressure leading to
different cardiovascular outcomes, despite similar effects on
Previously, the REASON study(2) demonstrated that a perindopril
(Coversyl)-based regimen reduces central systolic and pulse pressure
to a greater degree than the beta-blocker atenolol. This was found to
reflect a significant improvement of large artery function. Thus, in
addition to its other beneficial effects, such as improved
endothelial function, decreased vascular inflammation, and reduced
cardiac remodeling (a major cause of heart failure in elderly
patients), as demonstrated in the EUROPA(3,4) and PREAMI studie(5),
these beneficial vascular effects of perindopril at the level of
large arteries may have contributed to the decrease in cardiovascular
events seen in ASCOT.
The CAFÉ study found that in a group of 2073 ASCOT patients,
central aortic pulse pressure was significantly lower by 4.3 mm Hg
(P<0.0001) in the amlodipine / perindopril group throughout the
study, even though the brachial pulse pressure was similar in the two
groups. Central pulse pressure was a significant determinant of
cardiovascular events and renal impairment (P<0.05).
"The CAFÉ study demonstrates that antihypertensive treatment with
amlodipine and perindopril has a greater effect on central blood
pressure than older antihypertensives such as atenolol and
bendroflumethiazide, and this may well explain their superior effects
on outcome," commented Prof John Cockroft, Professor of Cardiology at
the Wales Heart Research Institute, University Hospital, Cardiff, UK.
"CAFE should also stimulate measurement of central blood pressure in
further large intervention studies, and perhaps in the future it will
be central blood pressure reduction that counts."
ASCOT was a major, landmark cardiovascular outcomes study showing
that amlodipine / perindopril treatment is significantly more
effective in reducing cardiovascular events than an older treatment
regimen: "The assumption has been that all types of blood pressure
treatment are equally effective at lowering blood pressure (in the
arm). We show that this assumption is untrue," says lead investigator
Prof Bryan Williams, MD, from the Department of Cardiovascular
Sciences, University of Leicester, UK. The CAFÉ results have
important implications and provide a mechanism to explain the better
clinical outcome for patients treated with amlodipine / perindopril
in the ASCOT study and the different effects of BP-lowering agents on
cardiovascular structure and clinical outcomes in other recent
Coversyl, which was discovered and developed by Servier, is
licensed worldwide for hypertension and heart failure at the dosages
of 4 to 8 mg. In the EU, the EMEA has given the go-ahead for a new
indication for Coversyl in stable coronary artery disease to reduce
the risk of cardiac events in patients with a history of MI and/or
revascularization. In the US, the FDA has just 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), PRESTARIUM(R), PREXANIL(R),
PREXUM(R), COVERENE(R), COVERSUM(R), PROCAPTAN(R), ARMIX(R), and
marketed by Solvay Pharmaceutical and CV Therapeutics under the
trade name of ACEON(R) in the USA.
Notes to Editors:
The ASCOT trial involved over 19 000 patients from the UK,
Ireland, and Scandinavia, and is endorsed by the British Hypertension
Society. All the patients had hypertension and at least three
prespecified cardiovascular risk factors, such as being over 55 years
old, being a smoker, and having a family history of coronary events.
The aim of the ASCOT trial was to test the hypothesis that a newer
antihypertensive regimen is more effective than an older regimen in
the primary prevention of coronary heart disease. The average length
of treatment was about 51/2 years.
The newer treatment strategy (the calcium channel blocker,
amlodipine, and the angiotensin-converting enzyme (ACE) inhibitor,
perindopril) offered such significant advantages over the older
treatment strategy (the b-blocker, atenolol, and the thiazide
diuretic, bendroflumethiazide) that the trial was stopped early by
the Data Safety Monitoring Board in December 2004. The ESC
presentation revealed that the perindopril + amlodipine treatment
combination significantly reduced the risk of death by any cause (by
11%), cardiovascular death (by 24%), stroke (by 23%), total coronary
events (by 13%), and new-onset diabetes (by 30%), compared with the
atenolol + bendroflumethiazide combination.
1. Dahlof B, Sever PS, Poulter NR et al, for the ASCOT
investigators. Lancet 2005; 366: 895-906.
2. Asmar RG, London GM, O'Rourke ME et al for the REASON
Project Coordinators and Investigators. Hypertension 2001;38:922-26.
3. EUROPA Study Investigators. Lancet 2003; 362: 782-788.
4. Ferrari R, et al. on behalf of the EUROPA trial investigators.
5. Cleland JGF, Coletta AT, Lammiman M et al. Clinical trials
update from the European Society of Cardiology meeting 2005: CARE-HF
extension study, ESSENTIAL, CIBIS-III, S-ICD, ISSUE-2, STRIDE-2,
SOFA, IMAGINE, PREAMI, SIRIUS-II and ACTIVE. Eur J Heart Fail.
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