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CARDIOVASCULAR JOURNAL OF AFRICA • Volume 30, No 2, March/April 2019
AFRICA
103
Beta-blocker target dosing and tolerability in a dedicated
heart failure clinic in Johannesburg
J Bolon, K McCutcheon, E Klug, D Smith, P Manga
Abstract
Background:
Despite the significant clinical benefits of beta-
blockers in heart failure with reduced ejection fraction
(HFrEF), prescription for and adherence to these agents is
reported to be poor. There are few data on the use and toler-
ance of beta-blocker therapy in patients with HFrEF in South
Africa and it is unknown whether these patients would benefit
from further heart rate-lowering therapy.
Methods:
Data from all patients with HFrEF attending
the heart failure clinic of Charlotte Maxeke Johannesburg
Academic Hospital from January 2000 to December 2014
were retrospectively collected. We first determined the rates of
beta-blocker intolerance in this population and then catego-
rised the patients according to their most recent dose of beta-
blocker (low, moderate or target dose) in order to identify
factors associated with beta-blocker intolerance. Lastly, we
used the data to identify patients who would be suitable for
further treatment with heart rate-lowering therapy.
Results:
Five hundred patients, with a median follow up of
58.7 months, were identified during the study period. Black
South Africans constituted the majority (66.4%) and most
patients had HFrEF due to hypertension (32.8%). At the
last recorded clinic visit at the end of the study period, 489
patients (97.8%) were taking a beta-blocker with 59.8%
prescribed a beta-blocker at target dose. Consistent with
previous data, bradycardia was the commonest cause for fail-
ing to reach target beta-blocker dose. Only 61 (12%) patients
were on no (
n
=
11) or low (
n
=
50) dose of beta-blocker at
final clinic visit. As per current guidelines, only 10.6% (
n
=
53)
of this cohort of patients would qualify for further treatment
with heart rate-lowering therapy.
Conclusions:
In a dedicated heart failure clinic in South Africa,
beta-blockers were well-tolerated in the treatment of HFrEF.
The potential role of specific heart rate-lowering therapy in
patients treated adequately with heart failure medication and
proper up-titration of beta-blockers is relatively small.
Keywords:
heart failure, reduced ejection fraction, beta-blocker
therapy, heart rate reduction, beta-blocker tolerability, ivabra-
dine
Submitted 2/10/18, accepted 7/1/19
Published online 11/2/19
Cardiovasc J Afr
2019;
30
: 103–107
www.cvja.co.zaDOI: 10.5830/CVJA-2019-001
The benefit of beta-blockers in chronic heart failure is well
established.
1
Major clinical trials have consistently shown reduced
rates of morbidity and mortality in patients with heart failure
with reduced ejection fraction (HFrEF) when beta-blockers are
included in the treatment regimen.
2-6
As a result, beta-blockers
have become an established first-line, best-practice treatment
in the management of HFrEF, as reflected in the guidelines of
major national and international cardiology organisations such
as the American Heart Association (AHA)/American College of
Cardiology (ACC) and European Society of Cardiology (ESC)
(adopted with minor modification by the Heart Failure Society
of South Africa, a special-interest group of the South African
Heart Association).
7-9
Despite the documented survival benefit, the percentage of
patients achieving target doses, as recommended in the guidelines,
is relatively poor.
10-12
For example, only 39% of patients with
primary prevention implantable cardioverter defibrillators for
cardiomyopathy were on ≥ 50 mg of carvedilol in a recent Danish
registry study.
13
Numerous reviews and surveys have shown that
beta-blockers have been under-used and under-dosed in heart
failure patients for various reasons,
14
with only 20 to 40% of
heart failure patients tolerating beta-blockers at target doses, and
the mean doses found to be only half the recommended target
dose.
10
Patients outside of large protocol-driven clinical trials
consistently failed to achieve target dose and/or target heart rate,
with surveyed physicians often reluctant to initiate or up-titrate
beta-blockers appropriately because of concerns about safety
and tolerability.
14
In light of the documented adverse effect on mortality of an
elevated heart rate, the demonstration of mortality benefit in
heart rate-reduction therapy, and the reluctance of physicians
to adequately prescribe and up-titrate beta-blockers at target
dose due to safety concerns, a pure heart rate-lowering agent
was sought.
15
Ivabradine, a selective I
f
current inhibitor, induces
dose-dependent heart rate reduction by directly reducing sino-
atrial node pacemaker activity. This agent has been studied in the
seminal SHIFT trial (Systolic Heart failure treatment with I(f)
inhibitor ivabradine Trial),
16,17
where 6 558 patients with chronic
heart failure, left ventricular ejection fraction
<
35%, and a
baseline heart rate (HR) > 70 beats per minute were randomised
to receive ivabradine or placebo. Patients were already meant to
be on optimal guideline-directed heart failure therapy (including
beta-blockers at maximally tolerated doses).
There is a paucity of data in South African patients regarding
the need for further heart rate-reduction therapy in patients
Division of Cardiology, Department of Internal Medicine,
Charlotte Maxeke Johannesburg Academic Hospital and
University of the Witwatersrand, Johannesburg, South Africa
J Bolon, FCP (SA)
K McCutcheon, FCP (SA)
E Klug, FCP (SA)
D Smith, FCP (SA)
P Manga, FCP (SA), PhD
Department of Cardiovascular Medicine, University
Hospitals Leuven, Leuven, Belgium
K McCutcheon, FCP (SA),
keir.mccutcheon@uzleuven.be