Cardiovascular Prevention and Pharmacotherapy

Original Articles

Variation in blood viscosity based on the potential cause of stroke of undetermined etiology: Jinyoung Oh, Youngchan Jung, Jin Kim, Sun Ki Min, Sang Won Han, Jong Sam Baik; Cardiovasc Prev Pharmacother. 2023;5(4):144-150. Published online October 25, 2023; DOI: https://doi.org/10.36011/cpp.2023.5.e14

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Abstract PDF: Background
This study investigated potential differences in blood viscosity (BV) among patients with stroke of undetermined etiology, negative evaluation (SUDn), specifically those with potential atherothrombosis (SUDn-AT) and those with possible embolism (SUDn-E).
Methods
This single-center study employed a retrospective observational design. The participants were patients over 20 years old with the SUDn stroke subtype who were admitted within 5 days of symptom onset. These patients were categorized as SUDn-AT or SUDn-E. Patients in the SUDn-AT group had nonsignificant stenosis (<50%) of a major brain artery relevant to their symptoms and exhibited one or more signs of systemic atherosclerosis, including atherosclerosis of at least one major brain artery other than those clinically relevant, coronary artery disease, and/or peripheral artery disease. For the SUDn-E group, the SUDn criteria from the TOAST (Trial of Org 10172 in Acute Stroke Treatment) classification system were strictly applied.
Results
The final analysis included 153 patients, with 104 (68%) classified as SUDn-E and the remaining 32% as SUDn-AT. Patients in the SUDn-AT group had a higher systolic BV (P=0.012) and diastolic BV (P=0.020) than those in the SUDn-E group. Multivariable logistic regression analysis revealed that age (odds ratio [OR], 1.08; 95% confidence interval [CI], 1.03–1.13; P=0.003), systolic BV (OR, 3.11; 95% CI, 1.41–6.85; P=0.005), and diastolic BV (OR, 1.08; 95% CI, 1.02–1.14; P=0.009) were associated with SUDn-AT.
Conclusions
Within the TOAST system, two SUDn entities may be distinguishable, with potentially different underlying etiologies: atherothrombosis and embolic stroke of undetermined source.

Fabry disease screening in young patients with acute ischemic stroke in Korea: Yunjung Choi, Taedong Ok, Kyung-Yul Lee; Cardiovasc Prev Pharmacother. 2023;5(2):54-60. Published online April 24, 2023; DOI: https://doi.org/10.36011/cpp.2023.5.e5

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Abstract PDF: Background
Fabry disease is an X-linked lysosomal storage disorder that results from a mutation in the α-galactosidase A (GLA) gene. It shows multiple organ involvement, including cerebrovascular disease. Since Fabry disease has a prevalence of approximately 4% in young patients with cryptogenic stroke, screening for this condition is recommended for young stroke patients. This study aimed to investigate the prevalence of Fabry disease in young acute ischemic stroke patients in Korea, the distribution of GLA gene mutations, and the subtypes of ischemic stroke.
Methods
This study included 211 young patients with acute ischemic stroke or transient ischemic attack. To screen for Fabry disease, α-galactosidase A (α-Gal A) enzyme activity was measured and DNA sequencing analysis of the GLA gene was performed.
Results
None of the patients exhibited low α-Gal A enzyme activity or had a pathogenic GLA mutation, but 18 nonpathogenic GLA gene variants were detected, including c.-10C>T in 16 patients, c.-33C>T in one patient, and c.196G>C in one patient. The mean α-Gal A enzyme activity in 14 male patients with the c.-10C>T variant was 5.17±1.19, which was significantly lower than that of male patients with the normal genotype (7.47±3.48, P<0.05). The distribution of stroke subtypes in patients with GLA gene polymorphisms was not significantly different from that in patients with a normal genotype.
Conclusions
This study demonstrates that Fabry disease is rare in young patients with ischemic stroke or transient ischemic attack in Korea, and we suggest that routine screening for Fabry disease may not be necessary for ischemic stroke patients.

Indirect comparison of nonvitamin K oral anticoagulants and left atrial appendage occlusion: Sung-Hwan Kim, So-Yoon Park, Seung-Sik Hwang; Cardiovasc Prev Pharmacother. 2022;4(1):18-25. Published online January 18, 2022; DOI: https://doi.org/10.36011/cpp.2022.4.e1

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Abstract PDF Supplementary Material: Background
Anticoagulation is important in atrial fibrillation (AF) patients to reduce the occurrence of thrombotic events. We evaluated the efficacy and safety of percutaneous left atrial appendage occlusion (LAAO) as an alternative to systemic anticoagulation through an indirect comparative analysis.
Methods
An indirect comparative analysis of nonvitamin K oral anticoagulants (NOACs) and LAAO was conducted. Comparisons were made using data from four landmark randomized clinical trials (RE-LY, ROCKET-AF, ARISTOTLE, and PROTECT AF). Using warfarin as the common comparator, an indirect comparison was performed using data from each trial, and the relative risk was calculated between NOACs and LAAO.
Results
NOACs and LAAO showed similar results for the reduction of stroke and systemic embolism, with a non-statistically significant trend favoring NOACs (hazard ratio [HR], 0.74; 95% confidence interval [CI], 0.37–1.46 for dabigatran; HR, 0.99; 95% CI, 0.50–1.92 for rivaroxaban; HR, 0.89; 95% CI, 0.45–1.74 for apixaban). Significantly fewer major bleeding and procedure-related complications were found in patients treated with apixaban compared with LAAO (HR, 0.45; 95% CI, 0.26–0.75). Cardiovascular death occurred more frequently in patients administered NOACs than in patients with LAAO (HR, 2.28; 95% CI, 1.03–5.10 for dabigatran; HR, 2.41; 95% CI, 1.09–5.42 for rivaroxaban; HR, 2.40; 95% CI, 1.10–5.36 for apixaban).
Conclusions
The rate of all-cause death was similar between NOACs and LAAO. Compared with LAAO, NOACs led to a nonsignificant numerical decrease in stroke and embolism in AF patients. Significantly fewer safety events occurred in patients treated with apixaban. LAAO significantly reduced cardiovascular death.

Review Articles

Antiplatelet Therapy for Secondary Stroke Prevention in Patients with Ischemic Stroke or Transient Ischemic Attack: Kyung-Yul Lee; Cardiovasc Prev Pharmacother. 2021;3(4):86-94. Published online October 31, 2021; DOI: https://doi.org/10.36011/cpp.2021.3.e10

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Abstract PDF: The risk of stroke recurrence is highest in the acute phase after transient ischemic attack (TIA) or ischemic stroke. Therefore, patients with TIA or ischemic stroke should be treated with antiplatelet medication for stroke prevention. The short-term use of dual antiplatelet therapy between 21 and 90 days may be considered in those with acute minor stroke or TIA and highrisk of recurrence. However, the long-term use of dual antiplatelet therapy is not recommended due to the risk of bleeding. The current stroke guideline does not specify the administration of an antiplatelet for the secondary prevention of ischemic stroke. However, as clinical studies progress, antiplatelet therapy may become a personalized treatment in the future.

Dose Selection of Non-Vitamin K Antagonist Oral Anticoagulants in Korean Patients with Non-Valvular Atrial Fibrillation: So-Ryoung Lee, Young Keun On; Cardiovasc Prev Pharmacother. 2020;2(1):1-10. Published online January 31, 2020; DOI: https://doi.org/10.36011/cpp.2020.2.e5

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Abstract PDF: Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia. In the Asian population, patients with AF have been shown to have increased risks of ischemic stroke and all-cause death compared to patients without AF by 3.34- and 2.61-fold, respectively. AF guidelines recommend oral anticoagulation (OAC) therapy in AF patients with a CHA₂DS₂-VASc score of ≥1 for men and ≥2 for women with non-valvular AF. After the introduction of non-vitamin K antagonist oral anticoagulants (NOACs) as a treatment for AF, their use has become widespread. Compared to warfarin, NOACs showed comparable efficacy for the prevention of thromboembolic events and superior safety in terms of bleeding complications, especially intracranial hemorrhage. Physicians should keep in mind considerations for optimal OAC therapy to achieve the best outcome. Furthermore, appropriate dose selection in order to achieve the best clinical outcome is an important issue in clinical practice. All NOACs do not have the same rules for dose reduction, and dose reduction of NOACs is primarily recommended according to the dose reduction criteria investigated in pivotal randomized control trials. In this review, we focus on the optimal dose of NOAC and summarize current guidelines and evidence for appropriate dosing of NOACs.

Original Article

CYP2C19 Polymorphisms and Smoking Status Affects Responsiveness to the Platelet P2Y12 Receptor Antagonist Clopidogrel: Sang Won Han, Yong-Jae Kim, Woo-Keun Seo, Sungwook Yu, Hyo Suk Nam, Sung Sang Yoon, Seo Hyun Kim, Jong Yun Lee, Jun Hong Lee, Yang-Ha Hwang, Jun Lee, Kyung-A Lee, Kyung-Yul Lee; Cardiovasc Prev Pharmacother. 2019;1(2):63-70. Published online October 31, 2019; DOI: https://doi.org/10.36011/cpp.2019.1.e8

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1 Citations

Abstract PDF

Background
The “comparison of triflusal and clopidogrel effects in secondary prevention of stroke based on cytochrome P450 2C19 (CYP2C19) genotyping (MAESTRO)” study was a prospective, multicenter, randomized, open-label, and blind genotype trial. We performed a subgroup analysis of the MAESTRO study to explore the relationship between VerifyNow P2Y12 assay with regard to CYP2C19 polymorphisms and smoking status in patients with non-cardiogenic ischemic stroke who underwent clopidogrel treatment.
Methods
For the study, patients treated with clopidogrel and who underwent VerifyNow P2Y12 assay was selected from the MAESTRO study.
Results
Of the 393 patients in 18 hospitals, 256 (65%) patients in 12 hospitals were entered for this subgroup analysis. P2Y12 reaction unit (PRU) was significantly lower and percent inhibition (% INH) was higher in the current smoking group than in the nonsmoking group (p<0.001). The same results were also observed in the good genotype group when compared with the poor genotype group (p<0.001). Among the groups, significant lower PRU and higher % INH was demonstrated in current smoking with good genotype group. However, there was no difference in PRU and % INH between current smoking with poor genotype group and nonsmoking with good genotype group, suggesting that clopidogrel activity was concurrently related to CYP2C19 polymorphisms and smoking status.
Conclusions
Regarding secondary stroke prevention, patients who were current smokers and had a poor genotype for clopidogrel metabolism may benefit from clopidogrel treatment similar to that in patients who were nonsmokers and had a good genotype.

Citations

Citations to this article as recorded by

Investigation of smoking on the antiplatelet response to clopidogrel: Unravelling the Smoker’s Paradox.
Frank A Plakogiannis, Jakob Weidmann, Blake Fraser, Justin Kwong, Diana Asi, Pratham Kumar, Madeleine Baldock, Jasmine Naamo, Ruhani Baluja, Rachelle Catanzariti, Stewart Yeung, Lisa Pont, Kylie Williams, Gabriele De Rubis, Kamal Dua, Nadeem Irfan Bukhari
Pathology - Research and Practice.2024; : 155290. CrossRef

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