LAUSR

We read with interest the cost-effectiveness study by Narasimhalu et al. [1], which evaluated the cost effectiveness of CYP2C19 genotype-guided antiplatelet therapy in an Asian population of patients presenting with acute ischaemic stroke with the aim of prescribing ticagrelor instead of clopidogrel to patients with CYP2C19 loss-of-function mutations. The base-case analysis reported that CYP2C19 genotype-guided antiplatelet therapy resulted in an incremental cost-effectiveness ratio of Singapore Dollar (SGD) 33,839 per quality-adjusted life-year (QALY), which is far lower than the cost-effectiveness threshold of one GDP per capita (SGD 87,000/QALY) as recommended by the World Health Organization. In fact, the sensitivity analyses had proven the robustness of the findings. The Food and Drug Administration (FDA) of the USA issued a black box warning in 2010 on clopidogrel prescribing label to warn that clopidogrel has reduced effect on platelet activities in patients with CYP2C19 loss-of-function mutation [2]. In addition, FDA advised that the use of other antiplatelet agents should be considered in those who are identified as poor metabolisers based on CYP2C19 genotype testing [2]. Furthermore, the Clinical Pharmacogenetics Implementation Consortium [3] recommended CYP2C19 genotype-guided antiplatelet therapy with a switch to an alternative antiplatelet agent such as ticagrelor, which is not affected by CYP2C19 polymorphism in patients identified as intermediate or poor metabolisers. However, the recommendation is mainly for acute coronary syndrome patients undergoing percutaneous coronary intervention, as at that point of time, there was no conclusive clinical evidence to support the use of ticagrelor in patients with acute ischaemic stroke or transient ischaemic attack. Despite that discussion of CYP2C19 genotype-guided antiplatelet therapy has been ongoing for years, it is surprising to note that there was no official recommendation on the utilisation of genotype-guided antiplatelet therapy among patients with ischaemic stroke from clinical practice guidelines, medical consensus, or position papers in Asian countries where the prevalence of CYP2C19 loss-of-function mutation is higher compared to European countries. For instance, despite two previous studies [4, 5] showing a prevalence of CYP2C19 loss-of-function mutation between 62% to 68% among Singaporean patients, there was no revision of the Singaporean clinical practice guideline [6] on the management of stroke, which had not been updated since 2009 to include specifications of CYP2C19 genotype-guided antiplatelet therapy for patients with ischaemic stroke. Similarly, in Malaysia, there were no specifications on the utilisation of CYP2C19 genotype-guided antiplatelet therapy in the 2012 Malaysian clinical practice guideline [7] on the management of ischaemic stroke despite a 2004 study [8] demonstrating a prevalence of CYP2C19 loss-of-function mutation of 58% among the Malaysian population. Likewise, although recent studies [9, 10], within the last five years, have reported a prevalence of CYP2C19 loss-of-function mutation between 52 and 58% in the Chinese population, the newly updated guideline on the clinical management of ischaemic cerebrovascular diseases by Chinese Stroke Association [11] did not provide recommendations for the use of genotype-guided antiplatelet therapy among patients with ischaemic stroke. Clinicians who have doubts over prescribing ticagrelor as dual antiplatelet therapy along with aspirin in patients This letter refers to the article available at https ://doi.org/10.1007/ s4026 1-020-00970 -y.