Coversyl(R) Protects Hypertensive Patients Against New-Onset Diabetes

Paris (ots/PRNewswire) -

- New Analysis of ASCOT-BPLA Data Identifies Major Predictors of
NOD Among Hypertensives

A new analysis of data from the landmark Anglo-Scandinavian
Cardiac Outcomes Trial - Blood Pressure Lowering Arm (ASCOT-BPLA)
published today in Diabetes Care has identified the major predictors
of new-onset diabetes (NOD) in patients with hypertension. In
particular, the data show that hypertensive patients allocated to
amlodipine and the ACE inhibitor perindopril (Coversyl(R), Servier)
were 34% (HR 0.64 95% CI 0.59 to 0.74) less likely to develop NOD
compared with those allocated to a beta-blocker/diuretic combination
(atenolol plus or minus thiazide).(1)

For the investigators, given the evidence from ASCOT-BPLA and
previous trials, it seems that the beneficial effect of the
amlodipine/perindopril regimen is largely a composition of the
protective effect of Coversyl, amlodipine playing a neutral role,
whereas atenolol and thiazide have adverse effects. The benefits of
perindopril on NOD have not always been seen with all other RAAS
inhibitors: - the recent analyses of the DREAM trial did not show a
significantly protective effect of ramipril against NOD(2). More
recently, in the STAR trial(3), an ACEI/CCB antihypertensive regimen
was superior to an ARB/thiazide diuretic in reducing the risk of
NOD.

"This new ASCOT-BPLA analyses provide robust evidence that
treating hypertensive patients with a regimen based on amlodipine and
perindopril in comparison to atenolol and thiazide significantly
reduces the risk of NOD," states Dr Ajay Gupta, lead author and
Research Fellow at the International Centre for Circulatory Health,
Heart & Lung Institute, Imperial College, London. "Unfortunately,
beta-blockers and diuretics, often in combination, are used
extensively worldwide. If we translate our findings into patient
numbers in the US for example, 250 000 cases of NOD each year related
to the use of beta-blocker and diuretic combinations could be
avoided. It therefore seems at best unwise to use these drugs in
preference to others such as a calcium channel blocker plus an ACE
inhibitor, particularly since the latter combination has been shown
to be more cost-effective."

Other determinants of NOD

The new analyses also showed that other major predictors of NOD
in patients with hypertension were baseline fasting plasma glucose
(FPG) level greater than 5 mmol/L, body mass index (BMI), serum
triglyceride and systolic blood-pressure (SBP). FPG was the most
powerful predictor, with risk increasing nearly six times for each
mmol/L rise above 5 mmol/L. The model developed from these data will
allow clinicians to accurately predict NOD among hypertensive
patients.(1)

Hypertension and type 2 diabetes

Observational data suggest that hypertension is a risk factor for
type 2 diabetes, and hence the two conditions frequently coexist.
This risk is variably affected by different classes of
antihypertensive medication. A recent metanalysis of 22 clinical
trials suggests that the association between antihypertensive agents
and incident diabetes is lowest for ACE inhibitors and
angiotensinogen-receptor blockers, followed by calcium channel
blockers and placebo, with beta-blockers and diuretics having a
diabetogenic effect.(4)

ASCOT-BPLA

ASCOT-BPLA was a major multinational trial involving over 19,000
hypertensive patients that compared the effectiveness of two
different treatment strategies at reducing cardiovascular events. The
newer treatment strategy (amlodipine and perindopril) offered such
significant advantages over the older treatment strategy (atenolol
and bendroflumethiazide) that the trial was stopped early by the Data
Safety Monitoring Board in December 2004.

The aim of the new analysis of ASCOT-BPLA data was to determine
the baseline predictors of NOD in a large population of patients with
hypertension and to develop a risk score to detect those at high risk
for NOD. Of 19,257 randomized patients in the study, 14,120 were
considered "at risk" of developing diabetes at baseline, and 1,366
(9.7%) subsequently developed NOD during follow-up (median duration,
5.5 years). Independent predictors of NOD were developed with a
multivariate Cox model, and these predictors were used to calculate
individual risk scores.

"Baseline FPG greater than 5mmol/l, BMI and the use of atenolol
with or without a diuretic were among the major predictors of NOD in
these patients," points out Dr Gupta. "The model we developed from
the ASCOT-BPLA data will allow accurate prediction of NOD among
hypertensive subjects."

Coversyl:

Coversyl, discovered and developed by Servier, is licensed
worldwide for the treatment of hypertension and heart failure.
Coversyl is also indicated for use in stable coronary artery disease
to reduce the risk of cardiac events in patients with a history of MI
and/or revascularization.

ASCOT is the 5th positive morbidity-mortality trial with
perindorpil alone or in association, making Coversyl the ACEI, and
the antihypertensive, with most evidence-based data. 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) ..

Notes to Editors

ASCOT (Anglo-Scandinavian Cardiac Outcomes Trial) involved over
19,000 hypertensive patients from the UK, Ireland, and Scandinavia
and was 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 5 1/2 years.

The early cessation of the study because of the clear health
benefits in favor of the amlodipineplus or minusperindopril
combination meant that there was not enough statistical power for the
primary end point (nonfatal MI + fatal CHD) to reach statistical
significance, although there was a trend towards a 10% reduction in
favor of the amlodipine plus or minus perindopril strategy.
Significant secondary end points included all-cause mortality,
cardiovascular mortality, fatal and nonfatal stroke, and total
cardiovascular events and procedures. New-onset diabetes was a
tertiary end point.

References

(1) Gupta AK, Dahlof B, Dobson J, Sever P, Wedel H, Poulter N.
Determinants of new-onset diabetes among 19,257 hypertensive patients
randomised in the ASCOT-BPLA trial and the relative influence of
hypertensive medication. Diabetes Care. 2008 Feb 11 [Epub ahead of
print]

(2) The DREAM Trial Investigators. Effect of ramipril on the
incidence of diabetes 10.1056/NEJMoa065061. N Engl J Med.
2006;355:1551-1562

(3) The STAR Trial Investigators. Differences in glucose
tolerance between fixed-dose antihypertensive drug combinations in
people with metabolic syndrome. Diabetes Care. 2006;29:2592 - 2597.

(4) Elliott WJ, Meyer PM. Incident diabetes in clinical trials of
antihypertensive drugs: a network meta-analysis. Lancet.
2007;369:201-207.

ots Originaltext: Servier
Im Internet recherchierbar: http://www.presseportal.de

Contact:
For further information, please contact: Leah Baldwin or Amy
Sharples, Tonic Life Communications, +44(0)207-798-9900 /
leah.baldwin@toniclc.com