Page 46 - SAJDVD 9.1

44 VOLUME 9 NUMBER 1 • MARCH 2012
REPORT SA JOURNAL OF DIABETES & VASCULAR DISEASE
due to an increase in the size of the ageing
population and an increase in incidence
of cardiovascular disease. There is also an
increase in the complexity of procedures and
patients (more co-morbidities).
Contrast-induced acute kidney injury
is defined as an impairment of renal func-
tion (or increase in serum creatinine levels >
25%) within three days of contrast admin-
istration, with no other discernible cause. A
risk score can identify high-risk patients prior
to the procedure. This includes elements
such as diabetes, contrast volume, serum
creatinine level above 132 mmol/l, anaemia
and hypotension. Also important are age,
dehydration, and the use of high osmolar
contrast media. Consequences include renal
impairment that peaks four to five days after
contrast administration, longer hospital stay,
increased cardiac morbidity, increased risk of
death and greater risk of longer-term mor-
tality.
Estimated or measured glomerular filtra-
tion rate (GFR) can be used to calculate a
safe dose of contrast medium [twice the
GFR (in ml) is a safe dose; maximum to be
used is four times the GFR]. Strategies to
prevent contrast nephropathy: withdraw
nephrotoxic drugs (NSAIDS, aminoglyco-
sides, etc), stop diuretics 48 hours before
the procedure, volume expansion over 12
hours pre-procedure with normal saline,
limit the dose of contrast, use iso-osmolar
contrast, not high osmolar. Bicarbonate and
N-acetyl cysteine usage is of uncertain ben-
efit but can be used, and even diluting the
contrast medium. Doctors need to be aware
of and vigilant for this condition.
Modern approach to anticoagulant
and antithrombotic therapy
Dr Darryl Smith
Clopidogrel has been tried and tested in
millions of patients with acute coronary
syndromes over the last 10 years and the
clinical relevance of genetically based clopi-
dogrel non-responders is not clinically sig-
nificant, except in patients at high risk of
stent thrombosis. This pragmatic view, pre-
sented by Dr Darryl Smith (Johannesburg),
did however carry the caveat of using the
newer agents, prasugrel or ticagelor, in spe-
cific patient groups.
‘Prasugrel could well be the drug of
choice in younger patients at higher risk
of thrombotic events, also in diabetic and
STEMI patients, and in those with stents
and a history of recurrent events. Caution
is however required when considering the
use of prasugrel in patients with prior cer-
ebrovascular events or transient ischaemic
events, those older than 75 years and those
with a low body weight of less than 60 kg.
Prasugrel in the TRITON-TIMI 38 trial was
more effective than clopidogrel in reducing
cardiovascular events but at a slightly higher
bleeding risk’,6 he noted.
Ticagrelor, not yet available in South
Africa, is a very effective drug. It is not a pro-
drug and its action is both of shorter dura-
tion and reversible. ‘It does however cause
dyspnoea and bradycardia, which restricts
its use in patients with this cardiac symp-
tom’, Dr Smith added.
‘We also need to note that there were
significant mortality benefits with ticagrelor
in the PLATO study, achieved with a minimal
increase in bleeding.’ Dr Smith noted that
while aspirin remains the cornerstone of
anti-thrombotic therapy, the newer agents
such as clopidogrel, prasugrel or ticagre-
lor should be used in addition to aspirin to
reduce platelet aggregation.
‘The field of anti-coagulation is excep-
tionally difficult to review in a brief presenta-
tion’, Dr Smith said. However, it is generally
accepted that greater anti-coagulation effi-
cacy comes at the price of increased bleed-
ing. ‘This generalisation has been disproved
by the ARISTOTLE7 trial of apixaban in atrial
fibrillation (AF), which achieved a significant
reduction in stroke and systemic embolism
without an increased bleeding risk. This
may well be the shape of things to come:
more effective protection from coagulation-
related events by agents that are also safer
to use’, he added.
‘Warfarin is extremely effective but it
is difficult to use, particularly in the frail
elderly who are at high risk of AF-related
stroke or systemic embolism. Registraries
show that less than 55% of these patients
are put on warfarin, because of concerns
around bleeding’, Dr Smith noted.
‘In the prevention of AF-related events,
the use of the CHA2 DS2 -VASc to define risk
of an embolic event, and the HASBLED
score to define risk of bleeding, can help to
individualise therapies using the three new
agents, dabigatran, rivaroxaban and apixa-
ban’, Dr Smith argued. Use of these agents
as front-line therapy for the prevention
of AF-related vascular events is currently
under vigorous debate.8,9
Complicating the use of these agents is
the differing doses required for the same
agent in different conditions. For example,
rivaroxaban in acute coronary syndromes
was trialed at 2.5 mg bid versus 5 mg bid,
but the recommended dose for atrial fibril-
lation patients is 20 mg daily. This is also
true for dabigatran, which has a different
dose in knee- and hip-replacement surgery
compared to its dosage in the prevention
of vascular complications of AF.
Finally a lack of head-to-head studies
makes the clinician’s task of therapeutic
selection more difficult. These drugs offer
a great deal of promise, as shown in the AF
clinical trials against well-controlled war-
farin (some three to six patients saved per
1 000), which could be even larger in the
real world of poor warfarin control’, Dr
Smith concluded.
Aspirin should be continued as anti-
thrombotic therapy in high-risk patients
undergoing surgery when clopidogrel is
discontinued – Dr Darryl Smith
The incretins: so much attention
at international meetings that a
review in South Africa is timeous
Dr Larry Distiller
Dr Distiller, co-ordinator of this specialist
meeting, set the pace in a thorough review
of topics presented at the meeting by
cautioning clinicians to evaluate incretin
usage critically. ‘It is clearly time to review
these agents, both the GLP-1 agonists and
the DPP-4 inhibitors as their international
status grows and they become more avail-
able on the South African market’, he
noted.
The defining characteristics of these two
classes of agents are the supra-physiological
levels of GLP-1s, attained by exenatide or
liraglutide treatment (the GLP-1 agonists),
and the physiologically stable levels of
GLP-1 attained by the use of DPP-4 inhibi-
tors. ‘The actions of the injectable GLP-1
agonists are therefore generally more pow-
erful than the oral DPP-4 inhibitors. The
incretins’ enhancement of glucose-induced
insulin secretion and the restoration of the
glucagon-suppression response are particu-
larly relevant, as glucagon is certainly the
forgotten hormone of type 2 diabetes’, he
said.
Referring to exenatide (twice daily) and
the more powerful once-weekly dosage not
yet available in South Africa, and to liraglu-
tide (once daily), Dr Distiller noted that their
promise is partially fulfilled by the fact that
the reduction in HbA1c levels (0.8–1% reduc-
tion depending on baseline HbA1c level) is
maintained over a two to three-year period