CARDIOVASCULAR JOURNAL OF AFRICA • Vol 21, No 6, November/December 2010
AFRICA
323
Special Report
New anti-coagulant therapies set to revitalise clinical
haemotology practice
Annual meeting of the Southern African Society of Thrombosis and Haemostasis
J AALBERS, P WAGENAAR, ERIC KLUG
Cardiovasc J Afr
2010;
21
: 323–326
Clinical and laboratory-based haematologists are likely to
experience more requests for advice and support from their
colleagues in cardiology, orthopaedics and neurology as the
impact of newly registered anti-coagulant therapies unfolds. This
is because the new anti-thrombotic and anti-platelet agents will
need to be understood on the basis of their individual attributes
and not as inter-changeable drugs within their respective class.
Also, usage of the new factor Xa inhibitors such as rivaroxaban,
and direct thrombin inhibitors such as dabigatran, while not
requiring monitoring for routine clinical practice, have differ-
ent effects on standard coagulation tests which may require
expert interpretation prior to surgery or percutaneous coronary
interventions (PCI), or to assess compliance with medication or
suspected over-dosing.
A practical approach to new anti-platelet agents
Dr Eric Klug, Sunninghill Hospital, Johannesburg
‘There is an association between bleeding events and long-term
mortality; the occurrence of a major bleeding event is associated
with a continued higher risk of death at one year’, Dr Eric Klug
noted. The key risk factors associated with bleeding risk include
impaired renal function, older age, female gender, preceding
anaemia and heart failure.
1
‘This list of course also overlaps
critically with the increased risk of ischaemic events’, Dr Klug
pointed out.
The choice of antiplatelet agents has expanded from aspirin
with its well-accepted role in primary and secondary prevention
of cardiovascular and cerebrovascular events to include new
agents such as clopidogrel, prasugrel and ticagrelor.
‘Concern has been expressed about prior aspirin use and
outcomes in acute coronary syndromes (ACS). This was recently
evaluated in data from 60 000 patients with ACS who partici-
pated in myocardial infarction clinical trials.
2
The increased
mortality found in patients taking aspirin prior to presentation
with an ACS was related to the inherent higher risk of these
patients rather than to any adverse effects of the aspirin’, Dr Klug
advised. With regard to preventing post-stent thrombosis, dual
anti-platelet therapy (DAPT) is the gold standard; aspirin is used
together with a thienopyridine such as clopidogrel, prasugrel or
ticagrelor.
‘These agents are very effective, but the problem with regard
to cardiovascular events after the stenting procedure is related to
withdrawal of dual anti-platelet therapy. In the largest study of
drug-eluting stent-associated thrombosis,
3
a higher incidence of
stent thrombosis occurred following the discontinuation of both
aspirin and clopidogrel (or other thienopyridine) within a short
period, relating to the drug discontinuation’, Dr Klug said.
‘It is clear that we should always try to maintain aspirin
therapy at least at 81 mg/day during and post stenting, and
also where possible delay non-cardiac surgery for at least three
months after the PCI. In the latter case, a risk remains, but the
delay of surgery is beneficial’, Dr Klug added. He noted that a
tapered withdrawal of the selected anti-platelet therapy to avoid
the so-called rebound phenomenon is not required and the clopi-
dogrel can be stopped abruptly.
4
The anti-platelet action of clopidogrel is lessened in patients
with homozygous genetic variations of the CYP2C 19 gene,
which can be significant in high-risk patients. ‘This is also true
for prasugrel as both are pro-drugs, requiring conversion via the
cytochrome P450 enzyme. However, as cardiologists, we cannot
wait for genetic studies; nor has it been shown that doing routine
genetic testing improves clinical outcomes. It is for this reason
that the FDA has taken the decision to warn clinicians about this
possibility, but not mandate genetic testing’, Dr Klug said.
Evidence for the additional value of prasugrel compared to
clopidogrel in achieving a greater reduction of stent thrombosis,
cardiovascular death, myocardial infarction and stroke in patients
with ACS undergoing PCI comes chiefly from the TRITON
TIMI 38 trial.
5
‘The benefits of prasugrel over clopidogrel
unfortunately occurred with an increased risk of major bleed-
ing, including fatal bleeding’, Dr Klug pointed out. ‘Subsequent
clinical use has helped define a group of patients who should
not be given the more potent thienopyridine (prasugrel) as being
those older than 75 years, or with a history of stroke/transient
ischaemic attack (TIA), or with a low body weight, less than 60
kg.’ Prasugrel can however be used for NSTEMI patients and for
STEMI patients treated with PCI.
Dr Klug presented insights on the newer oral anti-platelet
agents such as ticagrelor, which is more effective than clopido-
grel without the penalty of increased bleeding rates. Dyspnoea
J AALBERS, Special Assignment Editor
P WAGENAAR, Johannesburg correspondent
E KLUG, Sunninghill Hospital, Johannesburg
‘For all patients with stents undergoing surgery or other
revascularisation procedures, do not stop the low-dose
aspirin of 81 mg. If you have to, withdraw the thienopyridine
and reintroduce as soon as possible’
– Dr Eric Klug
