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CARDIOVASCULAR JOURNAL OF AFRICA • Volume 30, No 2, March/April 2019
104
AFRICA
with HFrEF. It is our hypothesis that most heart failure patients
tolerate guideline-mandated doses of beta-blocker therapy and,
if adequately up-titrated, will not need further rate reduction
with agents such as ivabradine. We therefore sought to investigate
target dosing and tolerability of beta-blockers in a heart failure
population at a tertiary public hospital in Johannesburg, South
Africa, in order to determine the need for additional heart rate-
lowering agents.
Methods
Ethical approval for our study was obtained from the Human
Research Ethics Committee, University of the Witwatersrand.
Clinical records of all patients attending the Heart Failure
Clinic at Charlotte Maxeke Johannesburg Academic Hospital
(CMJAH) in the period January 2000 to December 2014 were
retrospectively reviewed.
Files for all adult patients who attended the heart failure
clinic at CMJAH during this period were included. Data were
extracted from every file, even from those who had died, since
our focus was the dose of beta-blocker at their last visit. These
patients were referred to this specialist clinic with a diagnosis of
HFrEF (patients with heart failure due to other aetiologies, such
as valvular heart disease, do not attend the clinic), diagnosed by
a clinician at CMJAH or a referral hospital and confirmed by
transthoracic echocardiography demonstrating left ventricular
ejection fraction (LVEF)
<
50%. Demographic and clinical data
at first clinic appointment and at the last visit were recorded.
Patients were then categorised according to their beta-blocker
dosing at their last visit in order to determine the rates of beta-
blocker tolerance within this population and to identify factors
related to beta-blocker tolerance. Patients were categorised into
low-, moderate- and target-dose categories based on target
dosing in major trials (Table 1).
18
Since some patients had
access to atenolol only, and no target dose exists for atenolol in
heart failure, dosing was based on standard dosing in systemic
hypertension.
Statistical analysis
Descriptive statistical methods were used. Continuous variables
are expressed as means
±
standard deviations (SD) for normally
distributed data or medians with interquartile ranges (IQR) for
non-parametric data;
p
-values were calculated using the paired
t
-test. Data were analysed using SPSS Statistics
®
(version 22) and
p
-values
<
0.05 were considered to be significant.
Results
Five hundred patients fulfilled the inclusion criteria for the
study and were included in this analysis. Patients in the clinic
were managed according to local and international best practice.
Beta-blockers were routinely used and judiciously up-titrated to
target doses, as tolerated.
Baseline characteristics are shown in Table 2. Male patients
comprised 52.5% (
n
=
263) and the mean (SD) age of the
cohort was 55 (15) years. Black patients (66.4%) constituted
the predominant ethnic group of the study. Hypertensive heart
disease was the commonest cause of heart failure (32.8%),
followed by ischaemic heart disease (22%). Mean (SD) LVEF at
admission to the clinic was 27.3% (8.36).
Median follow-up duration (first appointment recorded at
clinic to last recorded visit) was 58.7 months (IQR 25–86). At
enrolment, 87% of patients (
n
=
436) were in sinus rhythm.
Table 1. Categorisation according to beta-blocker dosage
(total daily dose)
Beta-blocker
Low dose (mg) Moderate dose (mg) Target dose (mg)
Bisoprolol
<
5
5 to
<
10
10
Carvedilol
<
25
24 to
<
50
50
Metoprolol
<
100
100 to
<
400
400
Atenolol
<
50
40 to
<
100
100
Table 2. Baseline characteristics
Variable
Total cohort
Beta-blocker
intolerant
Ivabradine
suitable
Number
500
61
53
Age (years), mean (SD)
55.3 (14.9) 59.1 (17.3) 52.2 (14.7)
Male,
n
(%)
263 (52.5)
33 (54.1)
34 (64.2)
Follow-up duration (months),
mean (SD)
58.7 (43.8) 59.8 (50.9) 43.3 (39.1)
Causes of HF,
n
(%)
IHD
110 (22)
17 (27.9)
14 (26.4)
HT
164 (32.8)
17 (27.9)
16 (30.2)
PPCMO
61 (12.2)
12 (19.7)
1 (1.9)
HIV
21 (4.2)
1 (1.6)
4 (7.6)
Chemo
24 (4.8)
2 (3.3)
5 (9.4)
Alcohol/toxins
24 (4.8)
1 (1.6)
2 (3.8)
Myocarditis
12 (2.4)
1 (1.6)
0 (0)
Idiopathic/unknown
66 (13.2)
11 (18.0)
11 (20.8)
Ethnicity,
n
(%)
Black
332 (66.4)
37 (60.7)
33 (62.6)
Indian
32 (6.4)
6 (9.8)
6 (11.3)
White
124 (24.9)
18 (29.5)
12 (22.6)
Coloured
12 (2.4)
0 (0)
2 (3.8)
Asian
0 (0)
0 (0)
0 (0)
Atrial fibrillation, mean (SD)
64 (13.0)
7 (11.5)
NA
SBP (mmHg), mean (SD)
Initial
120.8 (20.6) 116.8 (20.4) 118.6 (14.5)
Last
116.3 (18.3) 109.8 (18.4) 111.6 (14.6)
NYHA (initial),
n
(%)
I
159 (31.8)
16 (26.2)
NA
II
258 (51.6)
33 (54.1)
37 (69.8%)
III
78 (15.6)
13 (21.3)
13 (24.5%)
IV
5 (1.0)
1 (1.6)
2 (3.8%)
Weight, initial, mean (SD)
78.5 (17.9) 76.4 (19.5) 78.1 (16.8)
eGFR, ml/min/1.73, mean (SD)
85.2 (34.3) 78.4 (24.0)
HR (bpm), mean (SD)
Initial (
n
=
496)
85.9 (15.1) 82.1 (14.9) 94.2 (15.7)
Last (achieved) (
n
=
480)
71.9 (11.3) 71.9 (14.2)
80.2 (8.5)
Other agents,
n
(%)
ACEI
469 (93.8)
53 (87)
50 (94)
MRA
449 (89.8)
52 (85)
49 (92)
Cardiac glycoside
63 (12.6)
10 (16)
8 (15)
Statin
206 (41.2)
25 (41)
24 (45)
ISMO
148 (29.6)
9 (14)
11 (21)
Hydrallazine
72 (14.4)
22 (36)
25 (47)
Thiazide
73 (14.6)
6 (10)
5 (9)
CCB
47 (9.4)
5 (8)
2 (4)
HF
=
heart failure; IHD
=
ischaemic heart disease; HT
=
hypertension; PPCMO
=
peripartum cardiomyopathy; HIV
=
human immunodeficiency virus; NYHA
=
New York Heart Association classification; eGFR
=
estimated glomerular
filtration rate; SBP
=
systolic blood pressure; HR
=
heart rate; BPM
=
beats per
minute; ACEI
=
angiotensin converting enzyme inhibitor; MRA
=
mineralo-
corticoid receptor antagonist; ISMO
=
isosorbide mononitrate; CCB
=
calcium
channel blocker; NA
=
not applicable.