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Clopidogrel is an anti-platelet medication often prescribed to patients who have had an ischaemic stroke, which occurs when the blood supply to part of the brain is interrupted or reduced, in order to prevent another.
To be effective, clopidogrel needs to be metabolised by the CYP2C19 gene. However, due to loss-of-function (LOF) mutations in the gene, some patients have a reduced ability to produce the active metabolite and therefore do not benefit from the platelet-inhibition properties of clopidogrel. This increases their risk of stroke while on the medication to 8.2%, compared to 3.4% in those who do not have LOF mutations.
While there is an alternative anti-platelet medication called ticagrelor that does not need to be metabolised by CYP2C19 to be effective, it is costlier than clopidogrel at around $4 per day, compared to clopidogrel’s $0.20 per day.
At 50% to 60%, the prevalence of LOF mutations is significantly higher in Asians, in comparison to Western populations, where less than 3% of Caucasians see similar difficulties in metabolising clopidogrel. Considering this significant difference, a team from the National Neuroscience Institute (NNI), led by Dr Kaavya Narasimhalu, Consultant, Neurology, NNI @ Sengkang General Hospital, studied the cost-effectiveness of prescribing ticagrelor to patients with LOF mutations as an alternative to clopidogrel, and of genotype-guided anti-platelet therapy in Singapore.
“We wanted to understand from a societal point of view whether a small upfront cost to test drug responsiveness would result in long-term cost savings,” explained Dr Kaavya.
In the general Singaporean population, their research found that the prevalence of LOF mutations was 61% - 65% of ethnic Chinese, 60% of ethnic Indian, and 53% of ethnic Malay residents having LOF mutations. It was also found that patients with LOF mutations who took ticagrelor had a 4.1% risk of having another stroke, compared to 8.2% when taking clopidogrel.
While some extra cost would be incurred with the prescription of ticagrelor and genotype testing, the potential cost of inpatient and outpatient care associated with second strokes was far more significant. As such, the team concluded that it is cost-effective to screen for resistance to clopidogrel in ischaemic stroke patients in Singapore, and to prescribe ticagrelor to those found to have LOF mutations to prevent secondary stroke.
“We hope our current and future work into precision medicine and the costs of implementing them will change the way medicine is practised, from a ‘one-size-fits-all’ approach to one that focuses on picking ‘the right drug for the right patient’,” said Dr Kaavya.
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