CARDIOVASCULAR JOURNAL OF AFRICA • Vol 24, No 4, May 2013
AFRICA
147
Drug Trends in Cardiology
Congress report: Cardiology and Diabetes at the Limits,
22–25 March 2013
The 15th At the Limits conference was
held in Cape Town under the auspices
of the Hatter Institute and organised and
chaired by Prof Derek Yellon of University
College London and Prof Lionel Opie of
the University of Cape Town. The meet-
ing was sponsored by AstraZeneca,
Bayer HealthCare, Boehringer Ingelheim,
Bristol-Myers Squibb, Discovery Health,
Medtronic, Novo Nordisk, Roche, Servier,
Takeda and the Coca-Cola Company.
Early programming of diabetes and
cardiovascular disease: an update
Alan
Lucas,
Institute
of
Child
Health,
University College London
Lucas discussed programming during foetal
development and the effect of diet in the
postnatal period, specifically comparing
breast milk and formula feeding. Although
better foetal growth is associated with better
cognitive function, accelerating the growth
of small infants in the postnatal period to
‘catch up’ is associated with increases in
blood pressure, obesity and risk of cardio-
vascular disease. It may therefore be neces-
sary to avoid encouraging weight gain by
overfeeding smaller babies.
Expressed breast milk does not represent
the composition of suckled breast milk
which changes during a feed and, in the
longer term, with the length of time that
breast feeding continues. Recognition of this
has led to the reformulation of infant feeds.
The
Lancet
lecture:
The renin–angiotensin–aldosterone
system: have we reached the limits?
Marc
Pfeffer,
Brigham
and
Women’s
Hospital, Boston, USA
Marc Pfeffer told how he had gone to
extraordinary academic lengths over many
years to undertake and publish over 100
studies dealing with the renin–angiotensin–
aldosterone system (RAAS) system to show
that in the end the more extensively studied
drugs were the cheaper ACE inhibitors. The
more modern ARBs now also have strong
supporting data.
Overall, both ACE inhibitors and ARBs
give a 20% reduction in mortality in vascu-
lar disease
.
The ARBs have specific data for
ACE-intolerant patients and for post-infarct
heart failure. Combining ACE inhibitors
and ARBs has not, on the whole, given
improvements except in one heart failure
study by Pfeffer.
He also pointed out that spironolactone
and eplerenone were very similar, and that
studies (including one by his group) were
under way to evaluate whether spironol-
actone provides the same benefits in heart
failure as the now well-established but much
more costly eplerenone. To obtain fund-
ing for this study, Pfeffer had to gain US
government support via NIH.
The direct renin inhibitors failed to give
any further benefit. ‘So we are at the limit
of blocking the RAAS system; we have tried
to inhibit more, with no benefit’, Dr Pfeffer
concluded.
This is a personal South African view
of the meeting. The full talks and slides are
accessible on the
Lancet
website, so inter-
ested CVJA readers can select any talks they
would like to see and hear.
Transcatheter aortic valve implantation
(TAVI) surgery: where are the limits?
Axel Linke, University
of Leipzig, Germany
In inoperable patients, TAVI, using
Medtronic core valve self-expanding pros-
theses, offers resolution of severe aortic
stenosis but with complications of stroke
(2.9%), major vascular complications (10%)
and major bleeding events (10%). TAVI has
proved better than balloon valvuloplasty
and superior to drug therapy in inoperable
patients.
The future includes valves that are
repositionable, retrievable and steerable.
Attempts are also being made to reduce
strokes by using filters to capture calcific
debris and to design valves that reduce
aortic regurgitation.
What is the future of cardiac inter-
vention: have we reached the limits?
StephanWindeker, Bern University Hospital,
Switzerland
In the COURAGE trial, PCI, which resulted
in a reduction in ischaemia, was associ-
ated with an improvement in longer-term
outcome. FAME II showed marked benefit
of PCI guided by FFR compared to medical
therapy, the endpoint being driven by urgent
revascularisation. The ISCHEMIA trial is in
progress and may clarify the best approach
to treatment.
The comparison of PCI with CABG in
SYNTAX showed that risk stratification
yielded different results in the different cate-
gories. Newer DES may influence future
outcomes. Though PCI and CABG seem to
offer similar benefits in left main coronary
artery (LMCA) stenosis, difficulties remain
in choosing the best treatment for patients
with multi-vessel disease. The EXCEL trial
is evaluating LMCA PCI vs CABG.
Effective STEMI treatment requires
improvements in the management net-work.
Bio-absorbable stents may result in posi-
tive remodelling of the coronary vessel.
The duration of dual antiplatelet therapy
(DAPT) remains an open question. One trial
is in progress which will compare standard
DAPT to ticagrelor, given with only one
month of aspirin.
Heart failure: where are the new
targets?
Martin Cowie,
the Royal Brompton Hospital,
London
There has been a progressive improvement
in heart failure survival over the past two
decades, with a currently low rate of mortal-
ity in societies able to provide modern treat-
ment. Treatment can be improved by attend-
ing to the delivery of care. Triple therapy
with ACE inhibitors, beta-blocker and MRA
are standard in HeF-REF. Ivabradine has an
important role in reducing hospitalisation
and improving quality of life.
New agents being investigated are sere-
laxin, which improves symptoms in acute
heart failure with 48 hours of treatment
but has no effect on re-admission rates.
Mortality at six months may be reduced.
Ultrafiltration is not beneficial, with more
adverse effects (Bart,
N Engl
J Med
2012).
Other areas of research are the effects of
mechanical circulatory support, autonomic
modulation with vagal stimulation or renal
denervation, the influence of sleep-disor-
dered breathing and cardiac myosin acti-
vators, ryanodine receptor stabilisers and
SERCA2a gene transfection of the myocar-
dium (CUPID 2a). Nonetheless the major
problem remains the lack of implementation
of known therapies.
