Amlodipine Based Regimen to Lower Blood Pressure, Reduces the Risk of New-Onset Diabetes in Hypertensive Patients by More Than a Third

Amlodipine Based Regimen to Lower Blood Pressure, Reduces the Risk of New-Onset Diabetes in Hypertensive Patients by More Than a Third

September 06, 2006

-- Issued on behalf of the Executive Committee of the Anglo-Scandinavian
Cardiac Outcomes Trial (ASCOT)

    BARCELONA, Spain, Sept. 6 /Xinhua-PRNewswire/ -- A
hypertension regimen based on the calcium channel blocker
amlodipine has been shown to reduce the risk of new-onset
diabetes by 34 percent in people with high blood pressure,
compared with a widely used beta-blocker-based
antihypertensive regimen, according to findings from the
largest study of hypertensive patients ever conducted in
Europe (nearly 20,000 patients). The results were presented
today at the World Congress of Cardiology in Barcelona.

    The Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT)
compared the regimen of the beta-blocker atenolol plus or
minus the diuretic bendroflumethiazide or the regimen of
the calcium-channel blocker, amlodipine plus or minus the
angiotensin-converting enzyme (ACE) inhibitor perindopril
for control of hypertension. 19,257 patients who enrolled
in the study, 14,120 did not have diabetes at the outset
and 1,366 of these patients developed diabetes over the
study period: 567 (8%) in the amlodipine arm and 799
(11.4%) in the atenolol arm.

    "One of the most important risk factors for
developing new-onset diabetes was being allocated to the
beta-blocker plus or minus diuretic treatment
strategy," Dr Ajay Gupta of the International Centre
for Circulatory Health, Imperial College London, UK, said.
"Patients allocated to the more modern blood
pressure-lowering strategy -- amlodipine plus or minus
perindopril -- were 34 percent less likely to develop
diabetes. This is important as diabetes significantly
increases the risk of myocardial infarctions (heart
attacks) and strokes."

    Additionally, the ASCOT study showed that patients who
received the beta-blocker based regimen were at increased
risk of new-onset diabetes irrespective of all other
diabetes risk factors, e.g. increased weight, blood glucose
at study entry and initial blood pressure level.

    Commenting on the results, Professor Neil Poulter, a
member of the Executive Committee of the ASCOT study, said:
"These findings have critically important implications
for many thousands of people. Hypertension already
increases the risk of diabetes 2-3 times. Now we know that
the commonly used combination of a beta-blocker plus or
minus diuretic significantly increases the risk compared
with a new combination, amlodipine plus or minus
perindopril. Physicians should think carefully before using
the beta-blocker based strategy to treat
hypertension."

    Results of the five-year ASCOT trial showed that
patients on the amlodipine based regimen experienced an 11
percent reduction in total mortality, a 23 percent
reduction in fatal and non-fatal strokes and a 24 percent
reduction in cardiovascular death, compared with patients
taking the beta-blocker-based regimen. In addition, they
had a 10 percent reduction in the primary endpoint of fatal
coronary heart disease and non-fatal heart attack, which did
not reach statistical significance as the study was halted
early due to the mortality benefit associated with the
amlodipine based regimen.

    A number of independent organisations, such as the UK
National Institute for Health and Clinical Excellence
(NICE), working with the British Hypertension Society, have
recommended that beta-blockers should no longer be the
preferred initial therapy for hypertension, and that a
calcium-channel-blocker or thiazide-type diuretic should be
the first choice for initial therapy in hypertensive
patients ages 55 or over, or in black patients of any age.
If therapy is initiated with a beta-blocker and a second
drug is required, a calcium-channel-blocker should be added
rather than a thiazide-type diuretic to reduce the patient's
risk of developing diabetes.(3)

    "This data highlights the additional risk of new
onset diabetes with a beta-blocker plus or minus diuretic
and provides support for this recommendation,"
Professor Poulter said.

    References

    Gupta AK on behalf of the ASCOT investigators.
Determinants of new onset diabetes using hypertension
patients questioned in the ASCOT-BPLA Trial, World Congress
of Cardiology, Barcelona, 6th September 2006.

    Dahlof B, Sever PS, Poulter NR, Wedel H et al.
Prevention of cardiovascular events with an
antihypertensive regimen of amlodipine adding perindopril
as required versus atenolol adding bendroflumethiazide as
required, in the Anglo-Scandinavian Cardiac Outcomes
Trial-Blood Pressure Lowering Arm (ASCOT-BPLA): A
multicentre randomised controlled trial. Lancet.
2005;366:895-906.

    3. NICE Clinical Guideline 34. Hypertension: Management
of hypertension in adults in primary care, June 2006.

    Note to Editors

    Funded by Pfizer, ASCOT was an investigator-led trial
coordinated by an independent steering committee. The study
began in 1998 and enrolled more than 19,000 patients in the
United Kingdom, Ireland, Sweden, Norway, Denmark, Finland,
and Iceland. In November 2004, the ASCOT steering committee
endorsed the recommendation of the Data and Safety
Monitoring Board to stop the trial early due to benefits
including mortality, demonstrated in patients who received
the calcium-channel-blocker-based regimen.

    In ASCOT, all patients had hypertension and at least
three pre-specified cardiovascular risk factors such as
being greater than or equal to 55 years old, a smoker and
having a family history of coronary events. The aim of the
ASCOT trial was to test the hypothesis that
calcium-channel-blocker-based antihypertensive treatment
regimen is more effective than a beta-blocker-based
antihypertensive regimen in the primary prevention of
coronary heart disease. The average length of treatment was
about 5.5 years.

    The early cessation of the study because of the
benefits of the amlodipine plus or minus perindopril
regimen in the secondary endpoint of all cause mortality
meant that there was not enough statistical power for the
primary endpoint (non-fatal MI + fatal CHD) to reach
statistical significance, although there was a
non-significant 10 percent reduction in favour of the
amlodipine plus or minus perindopril strategy. The
secondary endpoint included all-cause mortality,
cardiovascular mortality, fatal and non-fatal stroke, and
total coronary events and procedures all of which were
significantly reduced by the use of the newer regimen. New
onset diabetes was a prespecified tertiary end point.

    Norvasc (amlodipine besylate) is indicated for high
blood pressure and angina. In clinical trials, the most
common side-effects for Norvasc versus placebo were edema
(8.3% vs 2.4%), headache (7.3% vs 7.8%), fatigue (4.5% vs
2.8%), and dizziness (3.2% vs 3.4%).

    For more information, please contact:

     Alison Davies
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     Michael W Gibbs
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     Mobile: [phone]

SOURCE  Pfizer