Calcium Channel Blocker Rivals Beta Blocker in Preventing
Death, Stroke and Diabetes
New-onset diabetes lower with CCB
A calcium
channel blocker-based antihypertensive treatment
strategy in patients with coronary artery
disease is as effective as a -blocker-based strategy
in preventing death, acute MI, and stroke—and
significantly better at preventing new-onset diabetes,
according to a landmark clinical trial.
The 13% reduction in relative risk of new-onset
diabetes with a verapamil-based antihypertensive
regimen was a surprising finding of the International
Verapamil SR-Trandolapril (INVEST) trial and requires
confirmation in a prospective study. If it holds
up, the public health implications would be enormous
in light of the emerging epidemic of type 2 diabetes,
INVEST Principal Investigator Dr. Carl J. Pepine
declared at the annual meeting of the American College
of Cardiology.
INVEST involved 22,576 hypertensive patients with
documented coronary artery disease randomized at
862 sites in 15 countries to a non-dihydropyridine
calcium channel blocker-based antihypertensive strategy
with verapamil SR as the first drug, or a -blocker-based
one built upon atenolol.
The verapamil arm of the Abbott Laboratories-sponsored
trial featured the angiotensin-converting enzyme
inhibitor trandolapril as the second agent, or the
use of the combined tablet containing both drugs,
with the diuretic hydrochlorothiazide as the third
drug if required. In the atenolol arm, hydrochlorothiazide
was the second agent, in accord with long-established
published treatment guidelines, with trandolapril
reserved as the third drug when needed.
Two or
more antihypertensive drugs were required by 83%
of patients in each study arm. After a mean
of 2.7 years or nearly 64,000 patient-years of follow-up,
the primary combined study end point—death,
acute MI, or stroke—had occurred in 9.6% of
patients in the verapamil arm and 9.8% in the atenolol
arm.
This achieved the study's main goal: to prove whether
a calcium channel blocker-based treatment strategy
is an effective alternative to the long-established
-blocker-based approach to managing hypertension
in coronary disease patients. A calcium channel blocker
had not previously been put to the test in a large
trial with clinical end points, and some critics
had questioned the drugs' safety.
Given the poor job physicians are doing in controlling
hypertension around the world today, effective alternative
regimens are welcome, said Dr. Pepine, professor
of medicine and chief of cardiovascular medicine
at the University of Florida, Gainesville.
Roughly
1,200 cases of new-onset diabetes occurred during
the massive INVEST trial. The incidence was
6.2% in the verapamil arm compared with 7.3% in the
atenolol arm. The combined rate of another key secondary
end point—death or new-onset diabetes—was
11.9% with the calcium channel blocker-based strategy,
significantly less than the 13.4% incidence with
the -blocker-based approach.
Preliminary modeling suggests the explanation for
the reduced incidence of new-onset diabetes in the
verapamil group lies not in the increased use of
trandolapril in that study arm, nor with the use
of the calcium channel blocker; rather, the key factor
appeared to be the greater use of hydrochlorothiazide
in the atenolol arm.
Among other noteworthy findings in INVEST; patients
above age 70 had a primary event rate that was almost
threefold higher than that of patients below that
age, patients with a prior MI had an event rate nearly
identical to that of patients without prior MI, and
patients with prior heart failure had almost threefold
greater mortality than those without heart failure.
Blood
pressure control in INVEST was identical in both
study arms and was “spectacular,” said
Dr. Pepine.
