CARDIOVASCULAR JOURNAL OF AFRICA • Vol 22, No 1, January/February 2011
52
AFRICA
Chronic heart failure treatment benefits from pro-BNP-directed
therapy
The PROTECT study,
1
which was under-
taken to evaluate the benefits of tailor-
ing heart failure therapy according to
NT-proBNP levels, was stopped early
at the midpoint of the trial due to the
early benefits of this targeted biomarker
approach. Initially, the study planned to
recruit 300 patients with New York Heart
Association (NYHA) class II–IV systol-
ic heart failure [left ventricular ejection
fraction (LVEF)
≤
40%] but was stopped
after only 151 patients were recruited.
All the PROTECT patients received
standard-of-care heart failure therapy,
with clinically guided up-titration of
medication, while 75 patients had their
therapy adjusted to drive levels of amino-
terminal pro-B-type natriuretic peptide
(NT-proBNP) down to the pre-specified
target of
≤
1 000 pg/ml.
Nearly half of the patients in the guided-
therapy arm actually achieved the target,
and as a group they showed a signifi-
cant reduction in the primary endpoint
(
p
=
0.019) over a mean of 10 months,
compared with standard-of-care patients.
Their hazard ratio for the composite of
total cardiovascular events (worsening
heart failure, hospitalisation for heart fail-
ure, acute coronary syndrome, ventricu-
lar arrhythmias, cerebral ischaemia, or
cardiovascular death) was 0.44 (95%
CI: 0.22–0.84) after adjustment for age,
LVEF, NYHA class and renal function.
2
The results of the PROTECT trial were
presented at the recent American Heart
Association (AHA) 2010 congress. While
not yet published in a scientific journal,
fairly detailed results were released at the
meeting.
In his presentation at the AHA, Dr
James Januzzi of the Massachusetts
General Hospital noted that changes in
NT-proBNP were strongly associated with
the presence and severity of heart failure
and were markedly related to progression
of heart failure. NT-proBNP levels also
dropped in response to therapy. ‘However,
prior trials of NT-proBNP-guided therapy
have delivered mixed results. Also the
elderly have not responded as well as
younger patients’, he noted.
While patients in the NT-proBNP
arm were seen more frequently at the
heart failure clinic in order to drive
their biomarker levels down, up-titration
of drug therapy occurred in both the
standard-of-care and NP-proBNP arms,
showing that patients in the standard-of-
care arm also received aggressive ther-
apy. Interestingly, differences in thera-
pies occurred in the NT-proBNP-guided
arm, with a significantly increased use
of aldosterone antagonists and lower use
of loop diuretics. Forty-four per cent of
patients achieved the NT-proBNP target
level of less than 1 000 pg/ml.
In the NT-proBNP arm, a significant
reduction in total cardiovascular events
occurred (a drop of 50%), mainly driven
by a reduction in worsening heart failure
and heart failure hospitalisation. Primary
and secondary outcomes are summarised
in Table 1.
Therapies in both arms were well toler-
ated and importantly, patients older than
75 years of age showed similar benefits.
There was however an excess of hypoten-
sion in the NT-proBNP arm. The meas-
ured quality-of-life (QOL) parameters
improved in both arms, but a greater
improvement occurred in the NT-proBNP
arm.
In conclusion, Dr Januzzi pointed out
that the PROTECT results have shown a
very robust outcome and the benefits of
this guided approach, ‘if duplicated in
larger trials, indicate that NT-proBNP-
guided therapy may well represent a para-
digm shift in the treatment of the heart
failure patient’.
J Aalbers, Special Assignments Editor
1. Januzzi J. Benefits of natriuretic peptide
guided heart failure therapy for patients
with chronic left ventricular systolic
dysfunction: Primary Results of the pro-
BNP Outpatient TailorEd Chronic heart fail-
ure Therapy (PROTECT) study. American
Heart Association 2010 scientific sessions;
15 November 2010; Chicago, IL. Clinical
science: special reports I.
2. Heartwire special report. Slide 27. www.
clinicaltrialresults.org; slide 32, 33.
TABLE 1. PRIMARYAND SECONDARY OUTCOMES IN PROTECT
Parameter
NT-proBNP
guided,
n
=
75
Standard of
care only,
n
=
76
p
-value
NT-proBNP levels (pg/ml)
Baseline
2344
1946
NS
10-month follow up
1125
1
1844
0.03
Primary endpoint
2
events (
n
)
58
100
0.009
Patients with a primary event (%)
29.3
43.4 0.04
Quality of life,
3
rate of improvement by 10 points (%)
61.2
38.8 0.03
1
p
=
0.01 vs baseline.
2
Primary endpoint
=
total cardiovascular events (worsening heart failure, hospitalisation for
heart failure, acute coronary syndrome, ventricular arrhythmias (VT/VF), cerebral ischaemia,
or cardiovascular death.
3
As measured by the Minnesota Living with Heart Failure questionnaire.
