CARDIOVASCULAR JOURNAL OF AFRICA • Vol 21, No 2, March/April 2010
AFRICA
119
INVEST study warns on too-low BP in diabetic patients with CAD
The INVEST (INternational VErapamil
SR-Trandolapril) study, a very large inter-
national study of hypertensive patients,
has shown that patients with type 2 diabe-
tes and coronary artery disease do not
benefit from tightening systolic blood
pressure levels to below 130 mmHg, and
this may in some cases be harmful.
INVEST, initiated in the mid-nineties,
continues to contribute to the improved
management of patients with CAD and
this latest evaluation of the 6 400 patients
with diabetes and CAD included in the
INVEST cohort is the first study to criti-
cally evaluate the effects of systolic blood
pressure lowering in patients with both
diabetes and documented CAD.
These results are likely to require
guideline committees, including the
local SEMDSA’s guideline committee,
to include a warning that blood pressure
need not be driven below 130 mmHg in
diabetic patients as this does not result in
any further cardiovascular benefit.
This finding is particularly pertinent
to drug selection and the use of verapamil
SR/trandolapril, which was successful
with more than 70% of INVEST patients
reaching the target blood pressure of less
than 140/90 mmHg. The verapamil SR/
trandolapril therapy group also experi-
enced significantly fewer cases of new-
onset diabetes than those patients treated
with atenolol/hydrochlorothiazide.
‘Current guidelines suggest “lower is
better” with regard to blood pressure’,
said Rhonda M Cooper-DeHoff, PharmD,
MS, and associate professor of pharmacy
and medicine at the University of Florida,
Gainesville. ‘The INVEST data suggest
that in patients with both diabetes and
coronary artery disease, there is a blood
pressure threshold below which cardio-
vascular risk increases’.
For the study, INVEST randomly
assigned 6 400 patients with diabetes and
CAD to blood pressure-lowering therapy
based on either a calcium channel blocker
or a beta-blocker, plus an angiotensin
converting enzyme (ACE) inhibitor and/
or a thiazide diuretic. The target was a
blood pressure of
<
130/
<
85 mmHg.
For the analysis, patients were catego-
rised according to the degree of blood
pressure control actually achieved.
Patients with a systolic blood pressure
of 140 mmHg or higher, almost one-
third of patients, were classified as ‘not
controlled’. Those with a systolic blood
pressure below 130 mmHg were classi-
fied as ‘tight control’ and those with a
systolic blood pressure in between (
≥
130
mmHg, but
<
140 mmHg) were classified
as ‘usual control’.
During a follow-up period equiva-
lent to more than 16 893 patient-years,
researchers found that patients in the not-
controlled group had nearly a 50% higher
combined risk of death, heart attack or
stroke when compared with the usual-care
group. However, those in the tight-control
group had a similar risk to those in the
usual-control group.
Further analysis showed that lowering
systolic blood pressure below 130 mmHg
significantly increased the risk of all-
cause death when compared to usual care,
an increase that became apparent about
30 months into the study and persisted
for an additional five years of follow up.
When researchers then analysed blood
pressure in 5-mmHg increments in the
tight-control group, they discovered that a
systolic blood pressure below 115 mmHg
was associated with increased mortality.
‘Diabetic patients with CAD in whom
blood pressure is not controlled have
increased risk for unfavourable cardio-
vascular outcomes, so the message to
lower systolic blood pressure below 140
mmHg is still important’, Cooper-DeHoff
said. ‘However, it is not necessary to
lower systolic blood pressure below 130
mmHg to reduce that risk. Most impor-
tantly, reducing systolic blood pressure
below 115 mmHg may be associated with
increased mortality.’
J Aalbers, Special Assignments Editor
American College of Medicine. Press
1.
release.
end-stage renal disease or need for dialy-
sis. There was also no increase in severe
muscle aches/pains or rhabdomyolysis,
or evidence of liver damage’, Prof Sacks
noted. There was, however, a significant
reduction in micro- and macroalbuminu-
ria in the fenofibrate group, indicating that
diabetic nephropathy may be improved in
these patients.
TheACCORD trial was an independent
trial conducted by NIH specialist institutes
and the National Institute of Diabetes and
Digestive and Kidney Diseases (NIDDK).
Fenofibrate administration was masked
and administered at a dose of 160 mg per
day; adjusted according to the estimated
glomerular filtration rate. A total of 5 518
patients were enrolled in the ACCORD
LIPID arm.
The pre-specified primary outcome
was the first occurrence of a major
cardiovascular event, including non-fatal
myocardial infarction, non-fatal stroke or
death from cardiovascular causes. Mean
duration of follow up was 4.7 years for
the primary outcome. The results showed
that the combination was not better than
simvastatin alone in reducing the primary
outcome in the majority of the recruited
high-risk patients with type 2 diabetes.
‘While patients with atherogenic dysli-
pidaemia only represented 17% of the
ACCORD LIPID population, in everyday
clinical practice, the size of the problem
is significantly greater. We are now quan-
tifying this in the R³i-funded REsiduAl
risk LIpids and Standard Therapies
(REALIST) study, which is being
conducted at Harvard Medical School
and over 20 well-known academic centres
worldwide’, said Prof Frank Sacks, vice
president of the R
3
i.
J Aalbers, Special Assignments Editor
The ACCORD Study Group. Effects of
1.
combination lipid therapy in type 2 diabetes
mellitus.
New Engl J Med
March 14, 2010
(10.1056/NEJMoa1001282)
