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A survey on the treatment of atrial fibrillation in South Africa
1 Linmed Hospital, Benoni, Gauteng, South Africa
2 Sanofi, Midrand, Gauteng, South Africa
3
Milpark Hospital, Johannesburg,
South Africa
Background. The burden of cardiovascular disease is expected to escalate in developing countries. However, studies and guidelines concerning atrial fibrillation (AF) are restricted to the developed world.
Objectives. To assess the treatment modalities of AF in South Africa.
Methods. A cross-sectional, observational, multicentre, national registry of the treatment of 302 patients with AF was conducted from February 2010 to March 2011. Specific drug use for rate or rhythm control, as well as drug use for stroke prevention, was surveyed. Events during the 12 months prior to the survey were also characterised, including non-drug treatments, resource utilisation and complications.
Results. The single most prevalent clinical characteristic was hypertension (65.9%). Rhythm control was being pursued in 109 patients (36.1%) with class Ic and class III antiarrhythmic agents, while rate control, mainly with beta-blockers, was pursued in the remainder of the patients. Concomitant use of other cardiovascular drugs was high, and 75.2% of patients were on warfarin for stroke prevention. There was a high burden of AF-related morbidity during the preceding year, with 32.5% reporting a history of heart failure, 8.3% a stroke and 5.3% a transient ischaemic attack. Therapeutic success, as defined by either the presence of sinus rhythm or rate-controlled AF, was achieved in 86.8% as judged clinically by the treating physician, but in only 70.2% according to the electrocardiogram criterion of heart rate ≤80 bpm.
Conclusion. There were no striking
differences from previously reported registries worldwide. The
lack of application of strict rate control criteria is
highlighted.
S Afr Med J 2014;104(9):623-627.
DOI:10.7196/SAMJ.8111
Atrial fibrillation (AF) is the most common cardiac arrhythmia, with a prevalence of 5 - 6% in the 65-year-old population, increasing up to 10% in the >80 years population.1-4
Despite the improvement in
primary and secondary prevention of predisposing underlying
cardiac conditions such as ischaemic heart disease and
hypertension, the prevalence of AF continues to rise in
developed countries due to ageing and increasing obesity of
the population.3
,
5
,
6 The treatment of AF is
undergoing significant revision throughout the world and in a
number of ways, especially with regard to stroke prevention,
ablation for rhythm control, and novel antiarrhythmic drugs.
This has triggered a number of guidelines7
,
8 and guideline updates,9
,
10 as well as a number of
registries and surveys on AF and AF management in various
parts of the world (e.g. Nieuwlaat et al.
11 and Camm et al.12 ). In South Africa (SA), the
prevalence of AF in the urban black population has recently
been documented to be 7% in a cardiovascular disease cohort
(8% of heart failure patients, 4% of hypertensive patients,
and 13% of valvular disease patients).13 However, very little has been
published on AF management outside the developed world. This
prompted the Assessment of the Therapeutic Management of
Patients with Atrial Fibrillation in South Africa (SAFIR-RSA).
The principal objective of the study was to assess the
baseline characteristics of patients with AF and the treatment
modalities utilised, particularly the use of rate and rhythm
control strategies. The study also looked at hospitalisation
rates and prevention of thromboembolism.
Methods
SAFIR-RSA was a prospective
cross-sectional, non-interventional, observational disease
registry carried out in 29 medical institutions spanning nine
urban centres in SA. Patients were largely drawn from the
private insured medical sector and therefore represent a
relatively affluent stratum of the population.
Patients
The study protocol was approved by an independent ethics
committee, and written informed consent was obtained from
patients before study entry in accordance with Helsinki (1964)
ethical recommendations. Adult patients (≥21 years) with
electrographically documented AF were enrolled in the registry.
Patients were excluded if they had developed AF within 3 months
of cardiac surgery, had acute AF apparently precipitated by
non-cardiac conditions (e.g. pneumonia), or had recently
participated in an AF trial.
Procedure
A medical history taken at enrolment included recording each
patient’s treatment, the clinical
presentation of AF, the presence or absence of comorbidities,
and all data pertaining to the primary and secondary outcomes
(see below). The physicians or cardiologists in each
participating medical centre completed a standardised 6-page
case report form for every enrolled patient.
Primary evaluation criteria
These included: (i) the prevalence
of AF treatment modalities, namely the proportion of patients
receiving rhythm control agents (class I and III) and/or rate
control agents (class II and IV, and cardiac glycosides),
cardioversion, ablation or other procedures; and (ii) the use of treatments to prevent
thromboembolism, namely the proportion of patients taking
vitamin K antagonists, acetylsalicylic acid or other
antiplatelet agents. Any other cardiovascular treatments were
also noted.
Secondary evaluation criteria
These included: (i) the proportion
of patients with controlled AF, defined as either in sinus
rhythm (SR) (recorded during the visit) or at heart rate control
target (≤80 bpm at rest); and (ii)
the incidence of clinical outcomes in the year preceding the
inclusion, defined as hospitalisations for AF and other related
cardiovascular events such as stroke, transient ischaemic
attack, heart failure and myocardial ischaemia.
Statistical analysis
The data from all the participating medical centres were
combined and treated as one dataset for the purposes of the
analysis. Data analysis was performed with SAS statistical
software, Release 9.2 (SAS Institute, USA). Continuous variables
are reported as mean (standard deviation (SD)) and
non-continuous variables as number/percentage of patients. The
statistical analysis was mainly of a descriptive nature, and
sub-analyses were not prespecified in the protocol. Post-hoc
sub-analyses were performed using Fisher’s exact test. A p-value of <0.05 was considered
statistically significant.
Results
The study population consisted of 302 AF patients (59.9% male)
from 29 centres, enrolled from 18 February 2010 to 9 March 2011.
The mean age was 67 (SD 13) years (range 21 - 95). The mean
waist circumference was 101.6 (SD 17.8) cm and the mean body
mass index (kg/m2)
28.8 (SD 5.9), indicating a high prevalence of overweight
patients in the cohort.
Clinical characteristics
The single most prevalent clinical characteristic was hypertension (65.9%). Other coronary risk factors were also frequent (dyslipidaemia 48.3% and diabetes 15.6%). Concomitant structural heart disease was common, with 27.5% having valvular disease (of whom 79.5% had mitral valve disease), 26.8% coronary artery disease, and 32.5% heart failure; 28.5% of these patients had New York Heart Association class III or IV symptoms. In keeping with these comorbidities, 27.5% of patients had a history of previous cardiac or vascular interventions. Non-cardiac comorbidities were not common, comprising thyroid disease in 14.2% (3.3% hyperthyroid and 10.9% hypothyroid) and renal disease in 10.9% (Table 1).
The time course of AF was paroxysmal in 32.1% of patients, persistent in 21.2% and permanent in 46.7%. During the preceding 12 months, 40.7% of patients had experienced symptoms of AF.
Pharmacological treatment
The drug therapy at the time of the survey visit is listed in Table 2. For the purposes of this analysis, ‘rhythm control’ was defined as the chronic use of class Ic or class III drugs for the maintenance of SR, and all others were deemed ‘rate control’. Rhythm control was being pursued in 109 patients (36.1%) with class Ic and class III agents, while rate control was pursued in the remainder (63.9%). Amiodarone accounted for 79.4% of class III drugs used. A number of patients in the rhythm control group were receiving rate control medications in addition, but this number is not extractable from the data. Beta-blockers were the most frequently used rate control drugs. Combinations of beta-blockers, digoxin and rate-controlling calcium channel blockers were often employed. Concomitant use of other cardiovascular drugs was high, especially diuretics (53.0%), statins (44.0%), angiotensin-converting enzyme inhibitors (39.1%) and angiotensin receptor blockers (22.5%). For stroke prevention, 75.2% were on warfarin, 39.4% on aspirin and 5.0% on clopidogrel.
Events and hospitalisations in the preceding 12 months
Treatments for AF in the preceding 12 months included pharmacological cardioversion (17.5%), electrical cardioversion (13.2%), catheter ablation (4.2%) and pacemaker implantation (5.3%). Interestingly, a number of patients had an unusually large number of cardioversions in the previous year: 6 patients had two attempts at electrical cardioversion, 2 underwent three attempts, and a further 2 underwent four attempts. One patient had six pharmacological cardioversion attempts.
Of the total cohort, 104 patients (34.4%) had required hospitalisation during the previous 12 months, with a third of these patients requiring multiple hospitalisations. AF-related morbidity requiring hospitalisation was particularly frequent for heart failure (11.6% of study patients, 35/98 with heart failure), and for stroke, transient ischaemic attack and peripheral embolism (3.9% of study patients, 12/58 with these conditions) (Table 3). Haemorrhage occurred in 23 patients (7.6%) during the preceding year, but was considered to be serious enough to warrant hospitalisation in only 8 cases. One patient had intracranial haemorrhage. The mean duration of hospital stay was 5.2 days. The average number of outpatient consultations for AF or other cardiovascular reasons in the preceding year was 1.74.
Control of AF
The rhythm status
of
patients at the time of the survey is shown in Table 4. Only
85 patients (28.1% of the total study cohort) were in SR;
notably, 31 of these were on rate control medications alone.
Of the patients in AF at the time of the survey, 81.5% were
judged in the opinion of the enrolling investigator to be
satisfactorily rate controlled. However, when utilising a
strict electrocardiogram (ECG) criterion of rate ≤80 bpm, only
58.4% of patients in AF would fulfil this definition. Using
the ‘lenient’ rate control criterion of ≤110 bpm proposed by
the RACE II trial,8 90.6% of patients
would fulfil this definition. ‘Therapeutic success’ as defined
by either the presence of SR or rate-controlled AF was
achieved in 86.8% of the total population on the basis of the
clinicians’ clinical judgement, but only in 70.2% as judged by
the EGC criterion of rate ≤80 bpm.
A post-hoc sub-analysis was performed to compare the strategies of rhythm control with rate control (Table 5). Patients prescribed rhythm control medications were somewhat younger, had more medication changes in the preceding year, had more hospitalisations for AF or cardiovascular reasons, and underwent pharmacological and electrical cardioversion more frequently than the rate control group. The rhythm control group had significantly more hospitalisations for coronary artery disease (50.0% v. 16.3%), myocardial infarction (28.6 v. 0%) and heart failure (57.6% v. 25.8%).
Prevention of thromboembolic complications
The mean CHA2DS2-VASc score (congestive heart failure or left ventricular dysfunction, hypertension, age ≥75 (2 points), diabetes, stroke (2 points), vascular disease, age 65 - 74, sex category) for the entire cohort of patients was 3.08, and there was no significant difference in scores of patients on warfarin v. those not on warfarin (3.12 v. 2.96, respectively). Of patients not using vitamin K antagonists, 78.6% had CHA2DS2-VASc scores ≥2.
There was a poor correlation between the actual CHA2DS2-VASc score
and use of anticoagulation, as follows: score of 0 (65%); score
of 1 (83%); score of 2 (68%); score of 3 (76%); score of 4
(79%); score of 5 (76%); score of 6 (81%); score of 7 (25%, 1/4
patients); score of 8 (100%, 4/4 patients).
Discussion
The primary outcome measure in the SAFIR-RSA survey was to evaluate the incidence of AF treatment modalities and thromboembolic prevention treatments in a cross-sectional representative cohort of patients with AF in SA. The results clearly showed that the majority of patients were receiving rate control therapy (63.9%), usually in the form of beta-blockers, either alone or in combination with other rate control agents. Rhythm control therapy for the remainder of the patients consisted primarily of class III agents. Concomitant use of other cardiovascular drugs was high in both treatment strategies. Since the patient cohort included the elderly, with a high frequency of other cardiac risk factors and structural heart disease, it is not surprising that the majority were being treated with a rate control strategy. According to European Society of Cardiology guidelines, rate control is a reasonable strategy in elderly patients in whom the level of symptoms related to AF is deemed acceptable.8 Nevertheless, the findings do suggest that clinicians in SA apply lenient rate control criteria and judge patients to be rate controlled with a resting pulse rate of less than 110 bpm.
There were no striking differences in the baseline clinical characteristics of this study population when compared with other worldwide registries. Notably, the prevalence of underlying comorbidities such as coronary artery disease, valvular disease and heart failure in the present study is similar (~20 - 30% for each) to those reported in the developed world.8 This is perhaps not surprising because, although the aim of this study was to focus for the first time on SA patients, the cohort was largely derived (88.7%) from insured patients, a more affluent sector of the population that would more closely approximate a First-World setting. The racial groups of the subjects, frequently used as a proxy for socioeconomic status, are unknown.
The primary outcome measure of the SAFIR-RSA survey also included an assessment of the use of thromboembolic prevention treatments. The novel oral anticoagulants were not yet in use at the time of the survey. The findings show that the large majority of patients (75.2%) were receiving warfarin for stroke prevention. There were, however, a significant number of patients not receiving anticoagulation who, with CHA2DS2-VASc scores ≥2, should have had thromboembolic prevention therapy according to current treatment guidelines.10 Nearly all the patients on warfarin had had international normalised ratio monitoring during the previous 6 months. This diligent monitoring may account for the low rate of hospitalisation for haemorrhage of only 2.6% (8 patients) during the preceding year, compared with rates of 6.8 - 7.2% reported in other observational studies on older patients with AF receiving warfarin.14
In the present survey, hospitalisations
for coronary artery disease, myocardial infarction and heart
failure occurred more frequently in the group on
antiarrhythmic agents. It is not clear whether these
developments are a result of antiarrhythmic drug therapy, or
whether rhythm control is preferred as a strategy in patients
with these conditions.
Study limitations
There are a number of limitations to this study. The patient
sample does not necessarily reflect the true cross-sectional
population of AF patients in SA, as most had medical insurance
coverage. Site selection bias is likely, with
over-representation of cardiologists with specialisation or
particular interest in AF. Case selection bias may also have
been introduced because it was not mandated that consecutive
cases be included at each site. Investigator knowledge of the
sponsor may have introduced an additional bias in favour of
patients on amiodarone.
Conclusions
The data in the SAFIR-RSA survey conform to similar registries
in the developed world. Despite the focus on a relatively
affluent sub-sector of the SA population, resulting in a near
duplication of studies carried out in other developed countries,
this is the first epidemiological study generating data on
management of AF in SA. AF is a significant burden in cardiology
practice in this country, with considerable resource utilisation
and morbidity for patients. This survey highlights a lack of
rigour in applying definitions of rate control and
under-utilisation of antithrombotic therapy. Although only a
‘snapshot’, clinicians should be aware of these findings and
attempt to improve drug utilisation and patient outcomes.
Acknowledgements. This survey was
sponsored by Sanofi, Midrand, Gauteng, SA. Prof. Herman Schoeman
of Clinstat CC, Pretoria, SA, performed the statistical
analyses. Mrs Catherine Jardine provided secretarial assistance.
The following physicians and cardiologists are acknowledged for
their participation: M Alison, L Bushidi, G A Cassel, C Corbett,
A J Dalby, G C Ellis, C P Franklin, D J Gilmer, T J Gray, M
Heradien, J King, R D V Lamparelli, G Letcher, L Lombard, H
Louw, E Maree, J McKibbin, R Moodley, I W P Obel, A Okreglicki,
A Roodt, F A
Snyders, R Spammer, A Stanley, S N Thackersee, H Theron, N van
der Merwe, P D Whitfield, R Zeelie.
Conflict of interest. RMJ reports
receipt of a contractual fee from Sanofi-Aventis as Principal
Investigator, and also lecture fees and travel expenses from
Aspen Pharmaceuticals, Bayer Healthcare, Boehringer-Ingelheim,
Bristol-Myers Squibb, Cipla-Medpro, Medtronic and
Sanofi-Aventis. JF is a medical advisor at Sanofi. IWPO is a
consultant and investigator for Medtronic and has received
lecture fees and travel expenses from Medtronic,
Boehringer-Ingelheim and Bayer Healthcare.
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Accepted 20
June 2014.
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