24th-25th September <strong>2011</strong>Dr Mark ChanThe National Univesity Heart Centre, Singapore, togetherwith the Duke Cardiovascular Research Institute, USA, hostedSingapore’s first Antithrombotic Pharmacotherapeutics Symposiumfrom the 24th to 25th September <strong>2011</strong> at the new NationalUniversity Health System campus. International and local expertsupdated more than 250 doctors, nurses, pharmacists and industrydelegates on key clinical perspectives on the pharmacologicaltreatment of venous and arterial thrombosis.Antithrombotic therapy, comprising oral and injectableantiplatelet and anticoagulant agents, is the most widely prescribedclass of medications in clinical practice.The last 12 months have also seen a bumper crop of new drugstargetting the human platelet and coagulation system that havebegun an exciting new era of treatment options for thromboticdisorders.Drs Mark Chan and Chee Yen Lin, who co-chaired theconference, explains that there are two new revolutionary classesof antithrombotic therapy. The first belongs to the class of oralanticoagulants for prevention of stroke in atrial fibrillation, a verycommon disease of the elderly that can lead to debilitating strokesin as many as 10% of untreated patients. Warfarin, which has beenthe only useful drug for this condition for the last 5 decades,incurs a high risk of bleeding, including bleedinginto the brain, requires frequent blood tests andnecessitates strict adherence to dietary restrictions.Three new drugs, Rovaroxaban (Xarelto, Bayer),Dabigatran (Pradaxa, Boerhinger Ingelheim) andApixaban (Eliquis, Bristol Myers Squibb,) haveshown themselves to be as effective as warfarinin preventing strokes in atrial fibrillation but witha much lower risk of bleeding into the brain andwithout the need for regular monitoring blood tests.The second group of drugs belong to a class of drugs calledP2Y12 inhibitors. This class of drugs reduce the stickinessof platelets and prevent clogging of blood vessels after stentimplantation for a heart condition. For more than a decade, patientshad only one option in this drug class, clopidogrel. However, notall patients respond well to this drug and a failure to respond tothis drug can result in a rare but dreaded complication calledstent thrombosis in which a recently-implanted heart blood vesselstent clots suddenly and causes a major heart attack, frequentlyresuting in death. One reason for this poor response is the presenceof a genetic abnormality in the CYP2C19 system that convertsclopidogrel to the active form.Patients with one or more abnormal forms of this gene cannotgenerate the active compound as quickly as normal individuals.As such, their platelets remain more sticky and more prone toclogging up stents implanted in blood vessels supplying the heart.In a local study conducted on 400 patients seeking treatmentat the National University Hospital Dr Chan and colleagues showthat this abnormal gene is present in more than 40% of Indianpatients and close of 60% of Chinese and Malay patients. Thesefindings were presented at the International Society of Thrombosisand Haemostasis meeting in Kyoto, Japan this <strong>July</strong>.NUHCS PULSE | 18
The new P2Y12 – inhibiiting drugs, Ticagrelor (Brillianta,Astrat Zeneca) and Prasugrel (Effient, Eli-Lilly) reduce plateletstickiness more effectively and consistently in part because theybypass the CYP2C19 system of drug activation. Not only are thesenew drugs more expensive than clopidogrel, which is presentlygeneric, they can cause increased bleeding, so they may not besuitable for every patient.One possibility to do genetic testing to determine whichpatients may require the newer P2Y12 drugs. However, genetictesting itself can be expensive. Moreover, there are many otherdeterminants of response to clopidogrel, including age, bodyweight, renal function and diabetes. There is also the question ofwhether measuring the actual stickiness of the platelet itself, calledplatelet reactivity testing, is a better alternative.One of the symposium highlights was a hands-on plateletfunction testing workshop in which participants were trained inthe performance and interpretation of genetic tests and plateletreactivity tests.The APS meeting will be held every two years at differentlocations in South-east Asia. Through these meetings, Drs Chanand Chee hope to highlight and address some of the uncertaintiesin the use of these antithrombotic medications drugs and also equiphealthcare providers with practical yet thoughtful strategies fortreating patients with venous and arterial thrombotic disorders.NUHCS PULSE | 19