Vafa Alakbarzade1, Xuya Huang2, Irina Chis Ster3, Meriel McEntagart4, Anthony C Pereira5. 1. Royal Cornwall Hospitals NHS Trust, Neurology, Truro, United Kingdom; St George's University Hospitals NHS Trust, Neurology, London, United Kingdom. Electronic address: vafa.alakbarzade.10@ucl.ac.uk. 2. St George's University Hospitals NHS Trust, Neurology, London, United Kingdom. Electronic address: xuya.huang@nhs.net. 3. Institute of Infection and Immunity, St. George's University of London, London, United Kingdom. Electronic address: ichisste@sgul.ac.uk. 4. St George's University of London, Neuroscience, London, United Kingdom. Electronic address: meriel.mcentagart@stgeorges.nhs.uk. 5. St George's University Hospitals NHS Trust, Neurology, London, United Kingdom. Electronic address: anthony.pereira@stgeorges.nhs.uk.
Abstract
OBJECTIVES: To assess the prevalence of high on-clopidogrel platelet reactivity (HCPR) in patients with ischaemic stroke or transient ischaemic attack (IS/TIA), their outcome and genetic basis of on-treatment response variability in IS/TIA patients. METHODS: We conducted a comprehensive search of PubMed and EMBASE from their inceptions to March 9, 2019. Studies that reported absolute numbers/percentages of HCRP at any time point after IS/TIA onset evaluated with any type of platelet function tests, clinical outcomes and genotyping data were included. RESULTS: Among 21 studies of 4312 IS/TIA patients treated with clopidogrel, the pooled prevalence of HCPR was 28% (95%CI: 24-32%; high heterogeneity: I2 = 88.2%, p < 0.001). Heterogeneity degree diminished across groups defined by the HCPR testing method. Clopidogrel non-responder IS/TIA patients had poorer outcome compared to responders (RR = 2.09, 95%CI: 1.61-2.70; p = 0.036; low heterogeneity across studies: I2 = 27.4%, p = 0.210). IS/TIA carriers of CYP2C19*2 or CYP2C19*3 loss of function alleles had a higher risk of HCPR compared to wild type (RR = 1.69, 95%CI: 1.47-1.95; p < 0.001; I2 = 0.01%, p = 0.475). CONCLUSIONS: This systematic review shows a high prevalence of clopidogrel resistance in IS/TIA and poor outcome in these patients. CYP2C19 polymorphisms may potentially influence clopidogrel resistance. Crown
OBJECTIVES: To assess the prevalence of high on-clopidogrel platelet reactivity (HCPR) in patients with ischaemic stroke or transient ischaemic attack (IS/TIA), their outcome and genetic basis of on-treatment response variability in IS/TIA patients. METHODS: We conducted a comprehensive search of PubMed and EMBASE from their inceptions to March 9, 2019. Studies that reported absolute numbers/percentages of HCRP at any time point after IS/TIA onset evaluated with any type of platelet function tests, clinical outcomes and genotyping data were included. RESULTS: Among 21 studies of 4312 IS/TIA patients treated with clopidogrel, the pooled prevalence of HCPR was 28% (95%CI: 24-32%; high heterogeneity: I2 = 88.2%, p < 0.001). Heterogeneity degree diminished across groups defined by the HCPR testing method. Clopidogrel non-responder IS/TIA patients had poorer outcome compared to responders (RR = 2.09, 95%CI: 1.61-2.70; p = 0.036; low heterogeneity across studies: I2 = 27.4%, p = 0.210). IS/TIA carriers of CYP2C19*2 or CYP2C19*3 loss of function alleles had a higher risk of HCPR compared to wild type (RR = 1.69, 95%CI: 1.47-1.95; p < 0.001; I2 = 0.01%, p = 0.475). CONCLUSIONS: This systematic review shows a high prevalence of clopidogrel resistance in IS/TIA and poor outcome in these patients. CYP2C19 polymorphisms may potentially influence clopidogrel resistance. Crown
Authors: Shu Huang; Seonkyeong Yang; Shirly Ly; Ryan H Yoo; Wei-Hsuan Lo-Ciganic; Michael T Eadon; Titus Schleyer; Elizabeth Whipple; Khoa Anh Nguyen Journal: Eur J Clin Pharmacol Date: 2022-06-03 Impact factor: 3.064
Authors: Kosmas I Paraskevas; Dimitri P Mikhailidis; Hediyeh Baradaran; Alun H Davies; Hans-Henning Eckstein; Gianluca Faggioli; Jose Fernandes E Fernandes; Ajay Gupta; Mateja K Jezovnik; Stavros K Kakkos; Niki Katsiki; M Eline Kooi; Gaetano Lanza; Christos D Liapis; Ian M Loftus; Antoine Millon; Andrew N Nicolaides; Pavel Poredos; Rodolfo Pini; Jean-Baptiste Ricco; Tatjana Rundek; Luca Saba; Francesco Spinelli; Francesco Stilo; Sherif Sultan; Clark J Zeebregts; Seemant Chaturvedi Journal: J Stroke Date: 2021-05-31 Impact factor: 6.967