CARDIOVASCULAR JOURNAL OF AFRICA • Vol 22, No 2, March/April 2011
AFRICA
101
Simultaneous treatment of blood pressure and cholesterol beats
the ‘SILO’ approach in lowering cardiovascular risk: results of
the CRUCIAL study
The so-called ‘SILO’ treatment approach
based on the visualisation of individual
cardiovascular risk factors and result-
ing in one-at-a-time risk-factor treatment
is less effective than the simultaneous
targeting of the two major risk factors,
blood pressure and cholesterol.
This has been shown in the CRUCIAL
(Cluster Randomised Usual Care versus
Caduet Investigation Assessing Long-
term risk) study of moderately at-risk
patients with no prior history of coronary
heart disease (CHD) in which proactive,
simultaneous treatment of blood pres-
sure and cholesterol using a single pill
(amlodipine/atorvastatin) was compared
to usual care.
1
This carefully designed, prospec-
tive, multinational, open-label trial
with patients randomly designated to
either proactive or usual care showed a
greater relative reduction in calculated
Framingham 10-year risk after 52 weeks
of follow up. The mean CHD risk, which
was similar at the outset of the study
(actually higher in the proactive arm)
dropped to 12.5% in the proactive inter-
vention and 16.3% in the usual-care arm.
The difference was also observed by week
16 and maintained through to week 52.
The subjects recruited in the study,
which was conducted in Asia, Europe, the
United States and South America, includ-
ed typical at-risk patients. The mean age
was 60 years, 42% of the 1 461 patients
were diabetic with blood pressures of
150/90 mmHg and raised total cholesterol
levels
≤
6.5 mmol/l. They included equal
numbers of men and women.
Patients in the usual-care group could
be treated according to local protocols,
which may have included atorvastatin
and amlodipine. Patients in the proac-
tive group were treated with a single-pill
amlodipine/atorvastatin of 5/10-mg to
10/10-mg ratio. Subsequently, this could
be raised to 5/20 mg and 10/20 mg if
this dosage format was available in the
country.
Therapeutic lifestyle change was given
to all study participants and the clinicians
were instructed to target cholesterol and
blood pressure levels as recommended by
either the European guidelines or the US
NCEP guidelines. At the end of the study,
the mean final dose of study-provided
single-pill amlodipine/atorvastatin was
6.5/11 mg, respectively.
It is important to note that 58% of
the patients in the proactive-intervention
arm reached their JNC-7-based blood
pressure goal (140/90 mmHg, or 130/80
mmHg for those with diabetes) compared
to 47.5% in the usual-care arm. A greater
reduction in total cholesterol and LDL
cholesterol was seen at week 16 in the
proactive group, which was maintained
through to week 52.
The importance of this study is also
reflected in the fact that the patients
recruited were intentionally defined to
be similar to those who participated in
the ASCOT-LLA trial. This obviated the
need to provide clinical outcome data in
the CRUCIAL study as the long-term
benefit was well defined in ASCOT using
atorvastatin added to an amlodipine-
based antihypertensive regimen.
2
Also,
the Framingham 10-year CHD model was
chosen as it included diabetes as a risk
factor rather than a coronary heart disease
risk equivalent. This was also consistent
with the ASCOT-LLA approach.
It is important, finally, to note that
the adverse event profile in the proac-
tive-intervention arm was consistent with
previous safety experience using the
single-pill amlodipine/atorvastatin.
J Aalbers, Special Assignments Editor
1. Zamorano J, Erdine S, Pavia A, Kim JH,
et
al
. Proactive multiple cardiovascular risk
factor management compared with usual care
in patients with hypertension and additional
risk factors: the CRUCIAL trial.
Curr Med
Res Opin
2011;
27
(4): 821–833.
2. Sever PS, Dahlof B, Poulter NR,
et al
.
Prevention of coronary and stroke events
with atorvastatin in hypertensive patients
who have average or lower-than-average
cholesterol concentrations, in the Anglo-
Scandinavian Cardiac Outcomes Trial-Lipid
Lowering Arm (ASCOT-LLA): a multicentre
randomised controlled trial.
Lancet
2003;
361
: 1149–1158.
