Trial shows value of prompt blood pressure control
The VALUE trial design
VALUE was a randomised, double-blind, parallel
group study involving 15,245 hypertensive patients aged 50 years
or older. All had at
least one high risk feature such as coronary artery disease, previous
stroke, peripheral vascular disease or diabetes.
Patients were
started on valsartan 80mg or amlodipine 5mg and were titrated upwards
to 160mg and 10mg, respectively, if necessary. Hydrochorothiazide
could then be added, followed by other antihypertensives, excluding
ARBs.
The trial lasted for over four years at which point
1,450 patients had reached the primary endpoint — a composite of
cardiac mortality and morbidity. |
Lessons on prompt hypertension control may have been learnt from a study published this week. The VALUE trial (valsartan antihypertensive long-term
use evaluation) set out to compare the angiotensin receptor blocker
(ARB) valsartan with the calcium channel blocker amlodipine in hypertensive
patients at high risk of cardiac events.
The main outcome — a composite of cardiac mortality and morbidity — did
not differ between the groups. However, there were differences in secondary
endpoints that may be linked with more effective blood pressure lowering
with amlodipine, especially in the early part of the trial.
The researchers observed an increased incidence of myocardial infarction
and a non-significant trend to more stroke with valsartan compared with
amlodipine. Most of these events occurred in the first part of the study,
when blood pressure differences between the groups were at their greatest.
This “could give new insights into the clinical importance of the
rate of achieving BP control” the authors say. “The findings
suggest that recommended BP goals need to be reached within a relatively
short time (weeks rather than months) at least in patients with hypertension
who are at high cardiovascular risk.”
However, new-onset diabetes arose in fewer patients treated with valsartan
than amlodipine even though amlodipine is considered metabolically neutral.
The authors warn that, in high-risk patients, the immediate benefit of
BP lowering could override longer-term negative effects if drugs such
as diuretics and beta-blockers, which negatively affect glucose balance,
are used. “At a time when there is a pandemic of type 2 diabetes,
these findings from VALUE are especially relevant,” they state
(Lancet 2004;363:2022).
The researchers say that the differences in blood pressure may have prevented
fair comparison of the drugs, so they carried out a separate analysis
accounting for these differences. Most endpoints, including combined
cardiovascular events, myocardial infarction and stroke, did not differ
between groups. But heart failure was less common among patients treated
with valsartan. Blood pressure response after just one month’s
treatment predicted events and survival (ibid, p2049)
Fiona Reid, a primary care pharmacist for cardiovascular disease in Midlothian,
said the VALUE study reinforced the need for combination therapy. She
also noted that the target BP in the study was <140/90mmHg. British
Hypertension Society guidelines for current practice specify a target
of <130/80mmHg for this high risk group. The guidelines also advise
that drugs acting on the renin-angiotensin system should not be used
as first-line therapy in those aged 55 years or over. The mean age in
this study was 67 years. She added that it was interesting that VALUE
was the third trial to show a reduced incidence of new-onset diabetes
in hypertensive patients with an ARB. However, she said she would like
to see further evidence before changes in therapy were recommended, particularly
in view of cost implications of using ARBs, and because the majority
of patients in this group were on multiple drug regimens. |
The
Pharmaceutical Journal
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