Basic HTML Version
REVIEW
SA JOURNAL OF DIABETES & VASCULAR DISEASE
8
VOLUME 9 NUMBER 1 • MARCH 2012
study of rivaroxaban in acute coronary syndromes
10
were published,
showing reduced risk of the composite end-point of death from
cardiovascular causes, myocardial infarction or stroke with the use
of this new drug, although it increased the risk of major bleeding
and intracranial haemorrhage, but not the risk of fatal bleeding.
In the AVERROES study, apixaban (another anti-FX drug) was
compared with aspirin in patients with AF.
11
Apixaban 5 mg twice
daily was superior to aspirin, with a similar rate of major bleeding,
and was better tolerated than aspirin.
These drugs have not been approved in South Africa yet for use
in AF, but have been approved and successfully used as prophylactic
agents against deep-vein thrombosis in orthopaedic patients. In
view of the newer guidelines worldwide and experience in other
countries, many patients with AF and diabetes will probably receive
them in the future.
No laboratory testing is necessary with these two new drugs, but
routine laboratory assays may be used to determine the presence of
the drugs in cases of bleeding. With dabigatran, activated partial
thromboplastin time (PTT) and thrombin time (TT) may be used,
and in the case of rivaroxaban, prothrombin time (PT) may be used.
Specific assays to determine the level of the drug in the blood have
been developed, but in view of the predicted response and lack
of need for monitoring, these assays are not available in routine
laboratories.
No specific antidote is available for these drugs yet, but
fortunately both have a short half-life. Fresh, frozen plasma and
activated FVII (Novo VII) have been suggested as antidotes in a
patient who is bleeding and needs urgent reversal. Ideally, a fast-
acting antidote for these newer drugs would be welcomed.
Dabigatran may need dose adjustment if used with amiodarone,
and use is not recommended concomitant with quinidine. It should
also be used with caution with verapamil, clarithromycin, rifampicin
and other potent P-gp inducers. Rivaroxaban should not be used
with ketoconazole, itraconazole and HIV protease inhibitors,
and should be used with caution with fluconazole, phenotoin,
carbamzepine and other strong CUYP3A4 inducers. Considering
the many warfarin–drug interactions, these drug interactions are
few in number.
Combination therapy with antiplatelet and
anticoagulation drugs
The risk of bleeding increases with dual therapy consisting of
anticoagulants and antiplatelet drugs. It is even greater with triple
therapy where two antiplatelet drugs (aspirin and clopidrigel)
and an anticoagulant are used. There are however patients who
need this combination of the antiplatelet effect of aspirin (e.g.
underlying ischaemic heart disease) with anticoagulant therapy
(e.g. valve replacement, high-risk AF patients).
The ESC working group on thrombosis recommends that in
patients with atrial fibrillation who are on oral anticoagulants
and present with acute coronary syndrome and possibly stenting,
the following applies: with a CHADS
2
score of 0, patients should
receive dual therapy, and with a CHADS
2
score of 1 or more, triple
therapy is indicated. INR control must be kept between 2.0 and
2.5 with triple therapy. The duration of triple therapy depends on
the HASBLED bleeding risk, as well as type of procedure that has
been done.
12
The North American perspective
13
further suggests that aspirin,
if used in combination with oral anticoagulants, should be less than
100 mg and that a proton pump inhibitor (such as pantoprazole)
be given for the duration of therapy. It is also suggested that if the
newer drug dabigatran is used in combination with antiplatelet
therapy, the 110-mg instead of the 150-mg dosage be used. It is
recommended that the newer antiplatelet drugs such as prasugrel
and ticagrelor not be used with oral anticoagulant therapy.
Conclusion
Many new anticoagulant therapies have been developed and have
undergone testing in atrial fibrillation. New antiplatelet drugs have
also been developed. Many other novel drugs are at present being
tested in clinical trials. The time may come when more specific
therapy, tailored to each individual patient’s circumstances, will be
recommended.
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