Genotype Guided Antiplatelet Therapy in Ischemic Stroke
A fifth of ischemic stroke or transient ischemic attack (TIA) patients will have recurrent events within the first 3 months \[Refs 1-3\] despite aggressive medical therapy with antiplatelets and risk factor control. Clopidogrel is one of the mainstays of antiplatelet secondary prevention therapy in patients with ischemic stroke. CYP2C19 loss of function (LOF) mutations impair the effectiveness of clopidogrel \[Ref 4\]. The prevalence of LOF mutations is approximately 60% in the local population \[Ref 5\], rendering the effectiveness of empiric clopidogrel treatment doubtful. For patients who have LOF mutations, other treatment options for secondary prevention of ischemic stroke need to be tested. This study aims to determine the feasibility and clinical impact of genetic testing guided antiplatelet therapy in ischemic stroke patients on the prevention of major adverse cardiovascular or cerebrovascular events. Clopidogrel naive ischemic stroke or TIA patients aged 21 years and above will be randomised to genetic testing guided antiplatelet therapy or standard medical therapy within 7 days of their index event. Patients allocated to testing group will have blood sample drawn for diagnosis of CYP2C19 LOF mutations. Patients who test positive for an LOF mutation (intermediate and poor metabolisers) will be offered alternative antiplatelet therapy in the form of aspirn (for those who need monotherapy) or aspirin plus ticagrelor or dipyridamole (for those who need dual antiplatelet therapy) to be decided by the managing physician. Patients who test negative for LOF mutation will continue on clopidogrel. Platelet reactivity index (enables the identification of patients with an inadequate response to antiplatelet agents) will be measured at baseline.
• Patients diagnosed with acute ischemic stroke or transient ischemic attack.
• Age 21 years to 100 years.
• Can be randomised within 7 days of onset of index event \[Refer to footnote 1\].
• Clopidogrel naive immediately prior to index event \[Refer to footnote 2\].
⁃ Footnote 1: Date of index event to be taken as Day 1. This means that randomisation must be done by Day 7. For unknown onset or wake-up stroke where the last seen well and symptoms discovery are on different days, Day 1 is taken to be the date of symptoms discovery. Footnote 2: Patients who were on short-term antiplatelets which included clopidogrel but are no longer on clopidogrel prior to stroke would fulfil for this inclusion criteria. In this context, short-term antiplatelets are defined as 21 days for minor stroke TIA and 3 months for large vessel disease.