Abstract TP411: Effects of Triflusal and Clopidogrel in Secondary Prevention of Stroke Based on Cytochrome P450 2C19 Genotyping

Background: The relationship between stroke recurrence and cytochrome P450 2C19 (CYP2C19) genotype for the secondary prevention of ischemic stroke (IS) is not clearly defined. We investigated the effect of antiplatelet agents based on CYP2C19 genotype in secondary prevention of IS. Methods: In this prospective, multicenter, randomized, parallel-group, open-label, and blind genotype trial, we enrolled first non-cardiogenic IS patients within 30 days prior to screening at the 18 tertiary-care hospitals. Participants received 300 mg triflusal twice a day or 75 mg clopidogrel once daily. CYP2C19 genotyping was done in all patients and genotype results were blind during the study. The primary outcome was the time from randomization to first recurrent IS or hemorrhagic stroke. Efficacy analyses were performed using both the modified intention-to- treat population and the per-protocol population. The study is registered with ClinicalTrials.gov (NCT01174693). Results: This trial failed to meet its recruitment goal due to slow enrollment. A total of 784 (73% of required sample size) patients were followed for a mean of 2.5 years. In poor CYP2C19 genotype group (n=484), 30 (6.2%) patients had a recurrent stroke. The risk of recurrent stroke in triflusal group was 2.9% per year and was not significantly different with clopidogrel group (2.2% per year; hazard ratio [HR], 1.23; 95% confidence interval [CI], 0.6 to 2.53). In clopidogrel treatment group (n=393), 20 (5.1%) had a recurrent stroke. The risk of recurrent stroke in good CYP2C19 genotype was 1.6% per year and was not significantly different with poor genotype (2.2% per year; HR, 0.69; 95% CI, 0.26 to 1.79). Conclusions: In poor CYP2C19 genotype group, either triflusal or clopidogrel was not superior to the other in the prevention of recurrent stroke.

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Protocol for the comparison of triflusal and clopidogrel in secondary prevention of stroke based on cytochrome P450 2C19 genotyping (MASETRO study): A multicenter, randomized, open-label, parallel-group trial

International Journal of Stroke ◽

10.1177/1747493015620804 ◽

2016 ◽

Vol 11 (4) ◽

pp. 485-491 ◽

Cited By ~ 4

Author(s):

Sang Won Han ◽

Yong-Jae Kim ◽

Seong Hwan Ahn ◽

Woo-Keun Seo ◽

Sungwook Yu ◽

...

Keyword(s):

Cytochrome P450 ◽

Secondary Prevention ◽

Open Label ◽

Parallel Group ◽

Cytochrome P450 2C19 ◽

Parallel Group Trial ◽

Group Trial

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2014 Chinese guidelines for secondary prevention of ischemic stroke and transient ischemic attack

International Journal of Stroke ◽

10.1177/1747493017694391 ◽

2017 ◽

Vol 12 (3) ◽

pp. 302-320 ◽

Cited By ~ 24

Author(s):

Yongjun Wang ◽

Ming Liu ◽

Chuanqiang Pu

Keyword(s):

Ischemic Stroke ◽

Secondary Prevention ◽

Transient Ischemic Attack ◽

Recurrent Stroke ◽

Stroke Recurrence ◽

Evidence Based ◽

Cerebrovascular Disorder ◽

Level Of Evidence ◽

Vascular Stenosis ◽

Ischemic Attack

Ischemic stroke and transient ischemic attack (TIA) are the most common cerebrovascular disorder and leading cause of death in China. The Effective secondary prevention is the vital strategy for reducing stroke recurrence. The aim of this guideline is to provide the most updated evidence-based recommendation to clinical physicians from the prior version. Control of risk factors, intervention for vascular stenosis/occlusion, antithrombotic therapy for cardioembolism, and antiplatelet therapy for noncardioembolic stroke are all recommended, and the prevention of recurrent stroke in a variety of uncommon causes and subtype provided as well. We modified the level of evidence and recommendation according to part of results from domestic RCT in order to facility the clinical practice.

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Abstract P241: One-Year Cost-Effectiveness of Cytochrome P450 2C19 Genotype-Guided Antiplatelet Therapy in Patients With Acute Coronary Syndromes

Circulation Cardiovascular Quality and Outcomes ◽

10.1161/circoutcomes.4.suppl_1.ap241 ◽

2011 ◽

Vol 4 (suppl_1) ◽

Author(s):

Scott L Charland ◽

Barnabie C Agatep ◽

Daniel C Malone ◽

Eric J Stanek

Keyword(s):

Cytochrome P450 ◽

Cost Effectiveness ◽

Antiplatelet Therapy ◽

Annual Cost ◽

Extensive Metabolizers ◽

Cyp2c19 Genotype ◽

Event Management ◽

Test Cost ◽

Cytochrome P450 2C19 ◽

The Cost

OBJECTIVES: Cytochrome P450 2C19 (CYP2C19) genotype has been shown to affect cardiovascular (CV) outcomes for clopidogrel but not prasugrel. This study evaluates the cost-effectiveness of CYP2C19-guided vs. routine antiplatelet therapy in ACS patients. METHODS: We constructed a literature-based, decision analytic, Markov model (TreeAge 2009) to estimate the cost-effectiveness of CYP2C19-guided aspirin plus either clopidogrel or prasugrel therapy vs. no genotyping. Post-initial ACS CV events were based on the TRITON-TIMI 38 study and related costs were derived primarily using 2007 Healthcare Cost and Utilization Project DRGs for nonfatal MI and stroke, CV death, intracranial hemorrhage, other life-threatening bleed, and minor bleed. Additional costs and disease-state utilities were obtained from other published sources. All costs were adjusted to 2009 $US using the Consumer Price Index medical care component. The model allowed for clopidogrel/prasugrel discontinuation and aspirin monotherapy. Model sensitivity was assessed using 1-way and multi-way analysis of influential parameters. RESULTS: The base case model demonstrated that CYP2C19 genotype guided antiplatelet therapy yielded lower overall annual cost and greater efficacy vs. no genotyping ( Table ). The model was sensitive to (in declining order): clopidogrel cost/day ($1 to $5.78), prasugrel cost/day ($4.09 to $ 6.81), % CYP2C19 extensive metabolizers on clopidogrel (60% to 100%), CYP2C19 test cost ($60 to $250), and monthly CV event management cost. A threshold value for clopidogrel at <$2.14/day favored the no genotyping strategy. However, the genotyping strategy was dominant when clopidogrel cost =$1/day and a CYP2C19 test cost threshold of <$125 on 2-way analysis. CONCLUSIONS: CYP2C19 genotype-guided clopidogrel or prasugrel therapy is cost-effective for up to 1 year in ACS patients, and can remain a preferred strategy at a hypothetical generic clopidogrel cost of $1.00/day. Table Strategy1 Annual Cost Incremental Cost Quality Adjusted Life Year (QALY) Incremental QALY Cost/QALY Incremental Cost Effectiveness (ICER) CYP2C19 Genotype-Guided $ 3,211 0.7212 $ 4,452 No Gentoyping $ 3,331 $120 0.6767 - (0.0445) $ 4,921 (Dominated) 1Base case values:Drug wholesale acquisition cost/day: clopidogrel $4.62, prasugrel $5.45; Baseline post-ACS utility = 0.83; Monthly cost for post-CV event management = $351; CYP2C19 genotyping =$185; After genotyping: 80% of extensive metabolizers, 20% of intermediate metabolizers and 10% of poor metabolizers on clopidogrel; 80% on clopidogrel without genotyping; Willingness to pay = $200

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Abstract WP421: Pravastatin Can Reduce the Progression of Carotid Intima-media Complex Thickness: The Japan Statin Treatment Against Recurrent Stroke (J-STARS) Echo Study

Stroke ◽

10.1161/str.48.suppl_1.wp421 ◽

2017 ◽

Vol 48 (suppl_1) ◽

Author(s):

Masatoshi Koga ◽

Kazunori Toyoda ◽

Kazuo Minematsu ◽

Masahiro Yasaka ◽

Yoji Nagai ◽

...

Keyword(s):

Repeated Measures ◽

Recurrent Stroke ◽

Japanese Patients ◽

Statin Treatment ◽

Stroke Recurrence ◽

Control Group ◽

Open Label ◽

Usual Dose ◽

Reductase Inhibitors ◽

To Receive

Background and purpose: The preventive effect of 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins) on progression of carotid intima-media complex thickness (IMT) has been shown exclusively in non-stroke Western patients. The Japan Statin Treatment Against Recurrent Stroke (J-STARS) Echo Study aims to determine the effect of pravastatin on carotid IMT in Japanese patients with hyperlipidemia with noncardioembolic ischemic stroke. Methods: This is a substudy of the J-STARS, a multicenter, randomized, open-label, blinded-endpoint, parallel-group trial to examine whether pravastatin reduces stroke recurrence in patients with noncardioembolic stroke. The patients were randomized to receive pravastatin (10 mg daily, usual dose in Japan) (pravastatin group) or not to receive any statins (control group). Carotid ultrasonography was performed by well-trained certified examiners and the recorded data was measured centrally. The primary outcome was IMT change of the distal wall in a continuous 2-cm section on the central side of the common carotid artery bifurcation over 5 years of observation. The IMT change was compared using mixed models for repeated measures. Results: Of 1578 patients who were enrolled in the J-STARS, 864 were registered in this echo substudy. After excluding 71 without baseline ultrasonography, 793 (530 men, 66.4±8.3 years old) were analyzed. Of the 793 patients, 388 were randomly assigned to the pravastatin group and 405 to the control group. Baseline characteristics were not significantly different except baseline NIH Stroke Scale [median 0 (IQR 0-2) vs. 1 (0-2), p=0.019] between the two groups. The baseline IMT (mean±SD) was 0.887±0.155 mm in the pravastatin group and 0.887±0.152 mm in the control group (p=0.990). Each annual change of the IMT (mean±SD) over 5 years of observation was 0.011±0.085 mm, 0.023±0.114 mm, 0.017±0.114 mm, 0.018±0.118 mm and 0.021±0.116 mm in the pravastatin group and 0.008±0.074 mm (p=0.650), 0.020±0.087 mm (p=0.985), 0.017±0.097 mm (p=0.586), 0.030±0.113 mm (p=0.202) and 0.040±0.118 mm (p=0.018) in the control group. Conclusion: Japanese usual dose of pravastatin significantly reduced the progression of carotid mean IMT at 5 years in patients with noncardioembolic stroke.

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Cytochrome P450 2C19 (CYP2C19) genotype status is not associated with cure rates of dual therapy with rabeprazole and amoxicillin for Helicobacter pylori

Gastroenterology ◽

10.1016/s0016-5085(08)82922-8 ◽

2001 ◽

Vol 120 (5) ◽

pp. A587 ◽

Cited By ~ 1

Author(s):

Masakatsu Uchihara ◽

Namiki Izumi ◽

Osamu Noguchi ◽

Yasuhiro Asahina ◽

Nobuhiko Kanazawa ◽

...

Keyword(s):

Helicobacter Pylori ◽

Cytochrome P450 ◽

Dual Therapy ◽

Cyp2c19 Genotype ◽

Cytochrome P450 2C19 ◽

Cure Rates

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Symptomatic Intracranial Atherosclerosis: Natural History of Medical Management Beyond the Hyperacute Stage of Ischemic Stroke in the Post-SAMMPRIS Era

Journal of Stroke Medicine ◽

10.1177/2516608518774168 ◽

2018 ◽

Vol 1 (1) ◽

pp. 68-72

Author(s):

Anand G. Vaishnav ◽

Radhika A. Vaishnav

Keyword(s):

Ischemic Stroke ◽

Natural History ◽

Recurrent Stroke ◽

Imaging Techniques ◽

Tertiary Care ◽

Unfavorable Outcome ◽

Stroke Recurrence ◽

Atherosclerotic Stenosis ◽

History Of

Background: A major cause of ischemic stroke (IS) worldwide, especially in Asia, is intracranial atherosclerotic stenosis (ICAS), which is also associated with the high risk of recurrent stroke. Objective: The aim of our study was to determine the natural history of symptomatic ICAS ischemic stroke (ICAS IS) patients. Materials and Methods: We collected data on acute ICAS IS patients beyond the hyperacute IS phase to determine stroke recurrence and mortality at a tertiary care neurology hospital. Data were collected on basic demographics and traditional risk factors such as hypertension, coronary artery disease, diabetes mellitus, tobacco abuse, and hyperlipidemia, and statistical analysis was done. The primary endpoint was to measure the unfavorable outcome as defined by recurrent stroke or death from any cause. Results: The mean follow-up time for the total 87 patients was 24.5 months. Nine patients (10.3%) had an unfavorable outcome in the follow-up period; 2 (2.3%) of them had recurrent IS. Age was a predictor of the unfavorable outcome ( P = .0025), whereas hyperlipidemia was present more in patients with the favorable outcome ( P = .033). There was a tendency for patients with poor outcomes to have a higher National Institutes of Health Stroke Scale at their onset of stroke. Conclusions: Aggressive medical treatment was associated with a relatively low risk of recurrent stroke in our ICAS IS population. This study provides groundwork for larger studies that can take into account clinical and newer imaging techniques to improve secondary prevention in ICAS IS patients.

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Incidence of Drug Interaction When Using Proton Pump Inhibitor and Warfarin According to Cytochrome P450 2C19 (CYP2C19) Genotype in Japanese

The Thoracic and Cardiovascular Surgeon ◽

10.1055/s-0034-1383814 ◽

2014 ◽

Vol 63 (01) ◽

pp. 045-050 ◽

Cited By ~ 4

Author(s):

Motomi Shiono ◽

Kenji Akiyama ◽

Akira Sezai ◽

Shinji Wakui ◽

Haruka Kimura ◽

...

Keyword(s):

Cytochrome P450 ◽

Drug Interaction ◽

Proton Pump Inhibitor ◽

Proton Pump ◽

Cyp2c19 Genotype ◽

Cytochrome P450 2C19

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Residual Risk and Its Risk Factors for Ischemic Stroke with Adherence to Guideline-Based Secondary Stroke Prevention

Journal of Stroke ◽

10.5853/jos.2020.03391 ◽

2021 ◽

Vol 23 (1) ◽

pp. 51-60

Author(s):

Yuesong Pan ◽

Zixiao Li ◽

Jiejie Li ◽

Aoming Jin ◽

Jinxi Lin ◽

...

Keyword(s):

Risk Factors ◽

Ischemic Stroke ◽

Secondary Prevention ◽

Acute Ischemic Stroke ◽

Stroke Prevention ◽

Recurrent Stroke ◽

Antihypertensive Agents ◽

Residual Risk ◽

Stroke Recurrence ◽

Secondary Stroke Prevention

Background and Purpose Despite administration of evidence-based therapies, residual risk of stroke recurrence persists. This study aimed to evaluate the residual risk of recurrent stroke in acute ischemic stroke or transient ischemic attack (TIA) with adherence to guideline-based secondary stroke prevention and identify the risk factors of the residual risk.Methods Patients with acute ischemic stroke or TIA within 7 hours were enrolled from 169 hospitals in Third China National Stroke Registry (CNSR-III) in China. Adherence to guideline-based secondary stroke prevention was defined as persistently receiving all of the five secondary prevention medications (antithrombotic, antidiabetic and antihypertensive agents, statin and anticoagulants) during hospitalization, at discharge, at 3, 6, and 12 months if eligible. The primary outcome was a new stroke at 12 months.Results Among 9,022 included patients (median age 63.0 years and 31.7% female), 3,146 (34.9%) were identified as adherence to guideline-based secondary prevention. Of all, 864 (9.6%) patients had recurrent stroke at 12 months, and the residual risk in patients with adherence to guidelinebased secondary prevention was 8.3%. Compared with those without adherence, patients with adherence to guideline-based secondary prevention had lower rate of recurrent stroke (hazard ratio, 0.85; 95% confidence interval, 0.74 to 0.99; P=0.04) at 12 months. Female, history of stroke, interleukin-6 ≥5.63 ng/L, and relevant intracranial artery stenosis were independent risk factors of the residual risk.Conclusions There was still a substantial residual risk of 12-month recurrent stroke even in patients with persistent adherence to guideline-based secondary stroke prevention. Future research should focus on efforts to reduce the residual risk.

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Karakteristik dan Periode Kekambuhan Stroke pada Pasien dengan Stroke Berulang di Rumah Sakit Margono Soekardjo Purwokerto Kabupaten Banyumas

Jurnal Keperawatan Muhammadiyah ◽

10.30651/jkm.v3i1.1586 ◽

2018 ◽

Vol 3 (1) ◽

Author(s):

Meida Laely Ramdani

Keyword(s):

Ischemic Stroke ◽

Secondary Prevention ◽

Low Income ◽

Recurrent Stroke ◽

Sampling Technique ◽

Stroke Recurrence ◽

Stroke Patients ◽

Cross Sectional ◽

Post Stroke ◽

Duration Of Illness

Background: Patients who had stroke recurrence after the first stroke have a high risk of disability as well as high rates of morbidity and mortality. Incidence of stroke recurrence can be prevented by controlling risk factors and secondary prevention among post stroke patient, and also tent of the duration of the occurrence of recurrent stroke after the first attack. Objective: The purpose of this study was to determine the characteristics and stroke recurrence periods of post stroke patients.Methods: Cross sectional study design was used in this study. Total 73 recurrent stroke patients age 18-60 years old were selected using consecutive sampling technique. This study was conducted on patients during their follow up in the outpatient department of unit neurology, Margono Soekardjo Purwokerto Hospital during November-December 2015. The characteristics of the recurrent stroke patients include sex, age, education, occupation, and income. This study also describes type of stroke and duration of illness. The periods of recurrent stroke patients divided in to three time periods (≤ 6-month, 7-12 month, >12 month). Results: 73 recurrent stroke patients showed 56% were female, age group 39-60 years old was 97,5%, 60,3% have low education (below senior high school), 64,7% work as public and private employees. Income of respondents were low income 53,4%. Ischemic stroke was the majority (87,7%), no history family of stroke 64,4%, 1-5 years duration of illness and periods of stroke recurrence >12 month was 45,20%.Conclusion: Ischemic stroke is the biggest case of recurrent stroke, so that we need to emphasize the importance of secondary prevention including medication and treatment. Background: Patients who had stroke recurrence after the first stroke have a high risk of disability as well as high rates of morbidity and mortality. Incidence of stroke recurrence can be prevented by controlling risk factors and secondary prevention among post stroke patient, and also tent of the duration of the occurrence of recurrent stroke after the first attack. Objective: The purpose of this study was to determine the characteristics and stroke recurrence periods of post stroke patients.Methods: Cross sectional study design was used in this study. Total 73 recurrent stroke patients age 18-60 years old were selected using consecutive sampling technique. This study was conducted on patients during their follow up in the outpatient department of unit neurology, Margono Soekardjo Purwokerto Hospital during November-December 2015. The characteristics of the recurrent stroke patients include sex, age, education, occupation, and income. This study also describes type of stroke and duration of illness. The periods of recurrent stroke patients divided in to three time periods (≤ 6-month, 7-12 month, >12 month). Results: 73 recurrent stroke patients showed 56% were female, age group 39-60 years old was 97,5%, 60,3% have low education (below senior high school), 64,7% work as public and private employees. Income of respondents were low income 53,4%. Ischemic stroke was the majority (87,7%), no history family of stroke 64,4%, 1-5 years duration of illness and periods of stroke recurrence >12 month was 45,20%.Conclusion: Ischemic stroke is the biggest case of recurrent stroke, so that we need to emphasize the importance of secondary prevention including medication and treatment.

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