Cardiovascular Journal of Africa: Vol 31 No 5 (September/October 2020)

CARDIOVASCULAR JOURNAL OF AFRICA • Volume 31, No 5, September/October 2020

246

AFRICA

Globally, cardiovascular disease is the leading cause of morbidity

andmortality.

Historically, communicable disease has dominated

the disease profile in Africa. However, non-communicable

diseases in general, and cardiovascular disease specifically, is

increasing in Africa because of increasing urbanisation and

lifestyle changes.

2-5

Dyslipidaemia is a major modifiable risk factor for athero-

sclerotic cardiovascular disease.

6,7

Management of dyslipidaemia

in South Africa is sub-optimal in many cases. The most common

problems are inaccurate risk stratification and inappropriate

prescription of low-intensity statin therapy.

8-10

Frequent reasons

for low-intensity statin use include restricted access to high-

intensity statins, therapeutic inertia and fear of statin-associated

muscular symptoms.

In South Africa most patients attending public sector clinics

have access to low- and moderate-intensity statins (simvastatin

10–40 mg) only and require referral to tertiary-level hospitals

for higher-dose statins. Prescription of ezetimibe is generally

limited to specialist lipid clinics. Private sector patients often face

formulary restrictions as well. Ezetimibe is often not reimbursed

or attracts co-payments on many plans. At the time this research

was undertaken, monoclonal antibodies to PCSK9 were not

commercially available in South Africa.

Observational studies in South African cohorts such as

CEPHEUS SA,

DYSIS

and ICLPS

were not adequately

powered to determine the percentage of very high-risk study

subjects who were not at low-density lipoprotein cholesterol

(LDL-C) goal (1.8 mmol/l) despite maximum-tolerated statin,

with or without ezetimibe. Because of the challenges of treating

familial hypercholesterolaemia (FH), we included patients with

FH in this study, even though younger patients with FH

often have lower absolute cardiovascular risk in the short

term (10 years) than patients with established atherosclerotic

cardiovascular disease or diabetes mellitus.

CARDIO TRACK was a South African, multi-centre,

non-interventional, cross-sectional study of predominantly

private healthcare sector sites (15 sites) and a single public sector

site. A description of the study protocol has been published.

The primary objective was to assess the percentage of very

high cardiovascular risk patients on maximum-tolerated statin,

with or without ezetimibe, not reaching the LDL-C goal of

1.8

mmol/l, as defined by the 2016 European Society of Cardiology

(ECS)/European Atherosclerosis Society (EAS) guideline for

the management of dyslipidaemia

and the South African lipid

guidelines.

The LDL-C goal of

1.8 mmol/l in the ESC/EAS

guideline was derived following analysis of multiple outcome

and vascular imaging studies, indicating that lower on-treatment

LDL-C is associated with better outcomes.

Secondary objectives included an analysis of patients with

LDL-C

5 mmol/l, to identify and characterise patients most at

need of additional therapy due to their very high LDL-C level,

despite receiving aggressive therapy. Additionally, we determined

the percentage of patients not at target who were not receiving

ezetimibe and explored reasons why ezetimibe, which is a simple

and safe intervention, was not prescribed to these patients. In a

further analysis we evaluated patients who failed to reach target

despite receiving maximal-tolerated statin and ezetimibe, as such

patients would be considered candidates for addition of PCSK9

inhibitors.

To identify factors associated with good lipid control, we

characterised patients at goal, stratified by achieved LDL-C

level (LDL-C

1.8–1.0 mmol/l; LDL-C

1.0 mmol/l). Finally,

we modelled the impact of various interventions on LDL-C goal

attainment using four sequential models, which are described

below.

Methods

The study was conducted in accordance with the principles

laid down by the 18th World Medical Assembly Declaration

of Helsinki and all subsequent amendments, and the guidelines

for good epidemiology practice. The study was approved by

Pharma Ethics and the Human Research Ethics Committee

of the Faculty of Health Sciences, University of Cape Town.

The study was funded by Sanofi and Regeneron. The study

was designed by the first and last authors in conjunction with

PN, who was employed by Sanofi at the time of the study. The

authors analysed and interpreted the data.

Adult patients aged

18 years with very high cardiovascular

risk or FH, receiving stable maximum-tolerated statin therapy for

at least four weeks prior to their latest lipid profile, were eligible

for inclusion. Very high-risk patients were defined as those

with previous acute coronary syndrome (ST-segment elevation

myocardial infarction, non-ST-segment elevation myocardial

infarction, or unstable angina), coronary revascularisation

(percutaneous coronary intervention, coronary artery bypass

graft surgery, or other arterial revascularisation procedures),

stroke or transient ischaemic attack, peripheral arterial disease

(history of either intervention, surgery, amputation or symptoms

with low ankle–brachial index

0.9), calculated risk estimation

≥

10% for 10-year risk of fatal cardiovascular disease, diabetes

mellitus with target-organ damage such as proteinuria, and

diabetes mellitus with another major cardiovascular risk factor

such as smoking or hypertension. We also included patients with

definitive familial hypercholesterolaemia according to the Dutch

Lipid Clinic Network criteria.

Maximum-tolerated statin was defined as either the highest

licensed dose of a statin or the highest dose that a patient could

tolerate. For patients not at LDL-C goal and not receiving

the highest licensed dose of atorvastatin or rosuvastatin, the

reason why the dose was not increased to the highest licensed

dose or why a more potent statin was not prescribed needed

to be documented. Acceptable reasons for a patient taking a

lower statin dose included adverse events on higher doses or

concomitant medications that may necessitate lower statin doses,

such as verapamil, colchicine, amiodarone, digoxin, ticagrelor

and sacubitril/valsartan. Patients who were not at target, and

who were not receiving maximal doses of either atorvastatin

or rosuvastatin with no medically valid reason for the failure

to titrate were not eligible for this study. Maximum-intensified

lipid-lowering therapy was defined as a high-intensity statin,

either atorvastatin 40–80 mg daily or rosuvastatin 20–40 mg

daily, co-prescribed with ezetimibe 10 mg daily.

Sites were selected based on their potential to include the

required number of patients following completion of a feasibility

questionnaire. Investigators were required to consecutively

include all eligible subjects who consented to participation. Data

were collected at a single visit. No laboratory testing was done

specifically for this study and lipid values were extracted from

clinical records. Lipid profiles taken up to 12 months prior to the