In 2017 the Dutch Pharmacogenetics Working Group (DPWG) of the Royal Dutch Association for the Advancement of Pharmacy (KNMP)

Acute Myocardial Infarction

Combination therapy of clopidogrel with low-dose acetylsalicylic acid is the main oral antiplatelet regimen to prevent recurrent ischemic events after acute coronary syndromes. The functional genetic variant, CYP2C19, is a major contributor to the intervariability of response to treatment.

Cerebrovascular disease 

Clopidogrel is used for the secondary prevention of cerebrovascular events, reducing the  occurrence of new cerebrovascular accidents in patients with acute ischemic stroke. However, a substantial number of subsequent strokes still occur despite clopidogrel treatment due to interindividual variability in response to treatment. \cite{Pan_2017}\cite{Song_2020} 
Previous studies have shown that the CYP2C19 polymorphism influences the response and efficacy of clopidogrel for the prevention of cardiovascular events.\cite{Pan_2017} It is associated with an increase in cardiovascular risk and mortality in patients with coronary artery disease treated with clopidogrel, however, there are very few patient studies that determine whether the CYP2C19 genotype influences the preventive efficacy of clopidogrel in patients who have had a stroke. \cite{Pan_2017}\cite{Song_2020}\cite{Gower_2020} The recognition of CYP2C19 genotyping is important as it allows us a better selection of secondary prevention strategies. However, before requesting pharmacogenetic tests or platelet function studies, it is important to consider modifiable factors that may influence platelet function studies, such as the patient's dosing regimen, adherence to medication, and potential drug-drug interactions that may decrease the effectiveness of clopidogrel (proton pump inhibitors, lipophilic statins, and calcium blockers). \cite{Lyerly_2018}
Several studies have shown that a dual therapy of clopidogrel with aspirin reduces the appearance of new strokes. Recent studies demonstrated that among patients with transient ischemic attack or mild stroke, the use of aspirin and clopidogrel compared to aspirin alone reduced the risk of recurrent stroke only in patients who were not carriers of the CYP2C19 allele with loss of function. \cite{Pan_2017}\cite{Song_2020} In a genetic substudy (SPS3-genes) it was found that patients with a CYP2C19 loss of function allele had a higher risk of stroke recurrence compared to non-carrier patients. \cite{Lyerly_2018} A meta-analysis found a 1.92-times increased risk of stroke in carriers of the CYP2C19 loss-of-function alleles.\cite{Song_2020} Another meta-analysis proposes that carriers of the CYP2C19 loss-of-function allele may have an attenuated response to clopidogrel.\cite{Pan_2017}
In contrast to studies of patients with coronary artery disease, guideline recommendations regarding the use of the CYP2C19 genotype in the context of stroke are limited due to a lack of prospective evidence. \cite{Song_2020}\cite{Gower_2020} Prasugrel and ticagrelor have been shown to be more potent platelet inhibitors than clopidogrel. Genetic variations in CYP2C19 have little effect on the pharmacokinetics of prasugrel, however, it is contraindicated in patients with a previous stroke due to an increased risk of bleeding complications.\cite{Lyerly_2018} In contrast, ticagrelor may offer clinical utility in the treatment and prevention of stroke, but further studies are required to determine its role and efficacy in treatment. \cite{Gower_2020} Current secondary prevention guidelines from the American Heart Association recommend its use when aspirin is contraindicated. \cite{Lyerly_2018} The American Stroke Association Secondary Stroke Prevention Guide does not provide recommendations on therapeutic alternatives. \cite{Gower_2020} Genetic tests to guide prescription can be useful, however, its use is not yet recommended. \cite{Song_2020,Gower_2020,Lyerly_2018}

Conclusion