Clopidogrel Resistance Among Ischemic Stroke Patients and Its Risk Factors in Indonesia

Abstract

<p><strong>Objective</strong>. Clopidogrel is a common antiplatelet used as secondary prevention of ischemic stroke, known to have better efficacy than aspirin, with a equivalent safety profile. However, clopidogrel resistance is not uncommon but has not been widely studied in Asia. This study will further assess clopidogrel resistance and its risk factors.</p><p><strong>Materials and Methods</strong>. A cross-sectional study was conducted at Rumah Sakit Universitas, Indonesia, and Rumah Sakit Cipto Mangunkusumo, Indonesia in 2020-2021. All patients had had at least one episode of ischemic stroke. Clopidogrel resistance was assessed using a VerifyNow assay.</p><p><strong>Results</strong>. 57 subjects were enrolled in this study. We found 15.8% of subjects were clopidogrel resistant. Gender was significantly associated with clopidogrel resistance, with males having 80% lower clopidogrel resistance (OR 0.2 (95% CI 0.022 – 0.638); P=0.006). Meanwhile, smoking was not associated with clopidogrel responsiveness (P=0.051). We found no association between haemoglobin, blood glucose, HbA1c, cholesterol, liver enzymes, serum urea concentration or creatinine levels and clopidogrel resistance.</p><p><strong>Conclusion</strong>. Clopidogrel remains an effective treatment to prevent recurrent ischemic stroke in Indonesia. Further studies are needed to assess gene polymorphism and clopidogrel resistance, which may explain the findings of this study.</p>

Role of Cytochrome p450 in Clopidogrel Resistance in Indonesian Stroke Patients

“…The number of participants resistant to clopidogrel in this study was 16 (14.3%). These results were consistent with those of previous ones in Indonesia, with no difference in frequency (9 people, 15.8%) [5]. This differs from the results of the two studies.…”

“…The study found that clopidogrel resistance and sex were significantly correlated, with women having a 2.8 times higher risk than men. These results were supported by a preliminary study that showed that men had an 80% lower risk of resistance than women [5]. In addition, studies by Price et al showed a significant correlation between sex and clopidogrel resistance [16].…”

“…Disturbances in the metabolic stages of clopidogrel cause a decreased response (unresponsiveness) condition, known as clopidogrel resistance. In various studies, clopidogrel resistance was also referred to as high on-treatment platelet reactivity [5]. Clopidogrel resistance correlates with race and individual factors [6].…”

Correlation P2Y12 Genetic Polymorphism As Risk Factor of Clopidogrel Resistance in Indonesian Stroke Patients

“…Meanwhile, a previous study showed that clopidogrel resistance was high in stroke patients, varying from 28% to 44%. 22 In the pilot study by Hidayat et al, 23 the researchers found a consistently low resistance to clopidogrel. This showed that only 15% of clopidogrel metabolism still showed very good effectivity in Indonesia.…”

Aspirin and clopidogrel resistance; a neglected gap in stroke and cardiovascular practice in Iran: a systematic review and meta-analysis

“…It is important to determine an appropriate individual Aspirin dose to ensure optimal drug efficacy over time [ 19 ]. It has been reported that CR has not been extensively investigated in Asian communities to date [ 20 ]. This systematic review and meta-analysis was conducted on published papers on AR and CR in Iran as an example of a developing country in the Middle East region to portray understanding of the importance of this issue in clinical practice in developing countries.…”