 Few
things can make Benjamin Quirell's blood pressure jump
like the final seconds of the Kentucky Derby. Unfortunately,
the 52-year old horse racing enthusiast is hypertensive
to begin with. The combo of beta-blocker and thiazide
diuretic his doctor has him on do a decent job of keeping
his blood pressure down most of the time, but when it
comes to horse racing, he needs something with a little
more oomph. Fittingly, ASCOT — the Anglo-Scandinavian
Cardiac Outcomes Trial of antihypertensive treatments
— has the answer. The trial was started in 1997 but
was stopped early after a new combination therapy achieved
markedly better results than the standard beta-blocker/thiazide
diuretic combo.
The ASCOT trial, involving 19,343
patients, tested a regimen of the beta-blocker, atenolol,
and the thiazide diuretic, bendroflumethiazide, against
a novel combination of the calcium channel blocker,
amlodipine, and the angiotensin converting enzyme (ACE)
inhibitor, perindopril.
WINNING
COMBO
The full results will not be made public until March,
but researchers claim that the new amlodipine-perindopril
combination offered such significant benefits over atenolol
with bendroflumethiazide that the trial steering committee
ordered the research halted on November 18, 2004. The
trial had been due to continue until 2006.
This is the second and final arm
of the ASCOT study. The first, the lipid control arm,
measuring atorvastatin against placebo, was also stopped
early after the statin demonstrated significant benefits.
In that case, the trial was stopped after researchers
found a risk reduction over placebo of roughly one-third
for all stroke, heart attack and fatal coronary heart
disease, and a risk reduction in overall cardiovascular
mortality of about 10%.
"The results of the ASCOT trial
have been long awaited," said Dr Peter Sever, from Imperial
College London, co-chairman of the study. "It was really
the first trial to specifically look at a combination
of drugs. Most patients require more than one treatment
so it is silly to test single drugs."
"The results were so significant
that it was important to stop a trial early because
of important cardiovascular benefits to those patients
receiving newer drugs," he said. He added that most
patients would be advised to switch at followup appointments,
but cautioned against stopping beta-blockers too abruptly
as this could cause high blood pressure to rebound.
JUST
DOESN'T CUT IT
Discussing the poorer performance of atenolol and bendroflumethiazide,
Dr Sever said: "The implication is that the very commonly
used beta-blocker drugs are not as effective at preventing
the major complications of hypertension — strokes
and heart attacks and so on."
Indeed, it might be fair
to ask if the trial tells us more about the strengths
of amlodipine with perindopril, or about the weaknesses
of atenolol. A Swedish study published in The Lancet
this past November found atenolol little better than
placebo at controlling blood pressure, and the authors
expressed doubts about the suitability of atenolol as
a reference drug in hypertension studies. Concern is
also growing among cardiologists that atenolol could
increase blood sugar levels and even provoke diabetes.
Hopefully, the full results of the ASCOT study will
shed further light on this question.
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