Clopidogrel For Prevention Of Stroke Research Articles

Efficacy and Safety of Ticagrelor versus Aspirin and Clopidogrel for Stroke Prevention in Patients with Vascular Disease: A Systematic Review and Meta-Analysis

Introduction: Currently, it is still controversial to treat stroke with ticagrelor alone. The purpose of our study was to systematically review and analyze the efficacy and safety of ticagrelor on cerebrovascular outcomes in patients with vascular risk factors. Methods: The PubMed, Cochrane Library, and Embase databases were systematically searched using the keywords stroke, ticagrelor, clopidogrel, and aspirin to identify randomized controlled trials (RCTs). Primary outcomes included reported stroke, ischemic stroke, and complex events; the secondary outcome was hemorrhagic stroke. The safety outcomes included major bleeding events, major or minor bleeding, and intracranial bleeding. The pooled odds ratio (OR), hazard ratios (HRs), and 95% confidence interval (CI) were calculated. We used I² statistics to assess statistical heterogeneity. Results: This meta-analysis included 15 RCTs involving 63,865 patients. Compared to the control group, ticagrelor reduced the risk of stroke (OR: 0.90; 95% CI: 0.81–0.99, p = 0.03; I² = 3%), ischemic stroke (OR: 0.81; 95% CI: 0.74–0.90, p < 0.0001; I² = 0%). Ticagrelor was not associated with an increased risk of all-cause mortality (OR: 0.94; 95% CI: 0.84–1.06, p = 0.31; I² = 62%), major bleeding (OR: 1.06; 95% CI: 0.97–1.15, p = 0.20; I² = 17%), hemorrhagic strokes (OR: 1.22, 95% CI: 0.76–1.96, p = 0.41; I² = 0%), and intracranial hemorrhage (OR: 1.06; 95% CI: 0.78–1.43, p = 0.71; I² = 12%). There was an increased risk of major or minor bleeding with ticagrelor compared to the control group (OR: 1.40; 95% CI: 1.19–1.66, p < 0.0001; I² = 56%). Additional analyses demonstrated that ticagrelor reduced the risk of incident recurrent stroke (HR: 0.83; 95% CI: 0.75–0.93, p = 0.0009; I² = 0%), recurrent ischemic stroke (HR: 0.79; 95% CI: 0.71–0.89, p < 0.0001; I² = 0%) among patients with a history of acute ischemic stroke (AIS) or transient ischemic attack (TIA). There were no significant differences in safety outcomes. Conclusion: Ticagrelor is slightly better than clopidogrel and aspirin in preventing stroke, especially ischemic stroke, with significant safety risks. For patients with a history of AIS/TIA, the use of ticagrelor was superior to the use of clopidogrel or aspirin in reducing the risk of subsequent stroke. We believe that ticagrelor is a potential alternative to aspirin or clopidogrel in some cases, especially for patients with CYP2C19 deficiency.

An Interactive Pharmacogenetics Lesson Using PharmGKB To Individualize Pharmacotherapy Recommendations

PharmGKB is a user‐friendly online pharmacogenomics database that annotates clinical guidelines for optimizing drug therapy based on patient genotypes. The majority of guidelines in PharmGKB are based on the interindividual variability in cytochrome P450 (CYP) enzymes responsible for metabolizing drugs. By individualizing patient therapy according to CYP genotypes, there is potential to improve pharmacotherapy outcomes and minimize the risk of adverse events. Although there is growing interest amongst educators and students to integrate pharmacogenetic content into health science curricula, there is a lack of educational resources that teach students how to utilize resources such as PharmGKB to inform clinical decision making. The purpose of this study was to assess and disseminate a case‐based interactive lesson on pharmacogenetic‐based drug dosing principles that uses PharmGKB. Seventy‐one high school students participated in a two‐hour Zoom session as part of a four‐day Toxicology, Health, and Environmental Disease Program. The lesson was divided into a didactic lecture on pharmacogenetics followed by a group‐based analysis of hypothetical case scenarios. Case questions focused on genetic variation in CYP enzymes in the context of different clinical scenarios. Examples included the use of codeine for analgesia (CYP2D6) and clopidogrel for stroke prevention (CYP2C19). Assessment of student understanding was measured by percent gain in correct answers between pre‐ and post‐lesson polling questions. The first question focused on pharmacology concepts while the last two focused on genetics concepts. Students had high pre‐test scores on the pharmacology question having learned these concepts earlier in the program. For the additional two questions, there was a positive gain (42%) demonstrating an increase in knowledge during the lesson. Seventy‐eight percent of students would be ‘extremely likely’ or ‘very likely’ to recommend this activity. We propose that an interactive, group‐based activity can be used to teach basic principles of pharmacogenetics and empower students and educators to effectively use online drug resources.

Efficacy of Clopidogrel for Prevention of Stroke Based on CYP2C19 Allele Status in the POINT Trial.

Clopidogrel is an antiplatelet drug that is metabolized to its active form by the CYP2C19 enzyme. The CHANCE trial (Clopidogrel in High-Risk Patients With Acute Nondisabling Cerebrovascular Events) found a significant interaction between loss-of-function allele status for the CYP2C19 gene and the effect of dual antiplatelet therapy with aspirin and clopidogrel on the rate of early recurrent stroke following acute transient ischemic attack/minor stroke. The POINT (Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke Trial), similar in design to CHANCE but performed largely in North America and Europe, demonstrated a reduction in early recurrent stroke with dual antiplatelet therapy compared with aspirin alone. This substudy was done to evaluate a potential interaction between loss-of-function CYP2C19 alleles and outcome by treatment group in POINT. Of the 269 sites in 10 countries that enrolled patients in POINT, 134 sites participated in this substudy. DNA samples were genotyped for CYP2C19 *2, *3, and *17 alleles and classified as being carriers or noncarriers of loss-of-function alleles. Major ischemia consisted of ischemic stroke, myocardial infarction, or ischemic vascular death. Nine hundred thirty-two patients provided analyzable DNA. The rates of major ischemia were 6.7% for the aspirin group versus 2.3% for the dual antiplatelet therapy group (hazard ratio, 0.33 [95% CI, 0.09-1.21]; P=0.09) among carriers of loss-of-function allele. The rates of major ischemia were 5.6% for the aspirin group versus 3.7% for the dual antiplatelet therapy group (hazard ratio, 0.65 [95% CI, 0.32-1.34]; P=0.25) among noncarriers. There was no significant interaction by genotype for major ischemia (P=0.36) or stroke (P=0.33). This substudy of POINT found no significant interaction with CYP2C19 loss-of-function carrier status and outcome by treatment group. Failure to confirm the findings from the CHANCE trial may be because the loss-of-function alleles tested are not clinically important in this context or because the 2 trials had differences in racial/ethnic composition. Additionally, differences between the 2 trials might be due to chance as our statistical power was limited to 50%. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00991029.

In patients with stroke, is warfarin better than aspirin plus clopidogrel for secondary prevention of stroke?

In patients with stroke, is warfarin better than aspirin plus clopidogrel for secondary prevention of stroke?

Implications of Pharmacogenetic Testing for Patients Taking Warfarin or Clopidogrel

Our knowledge of the pharmacogenetics of warfarin and clopidogrel continues to expand as we learn more about the individual genetic variations that contribute to the drugs' efficacy and toxicity. We aim to review the recent developments in the field and discuss the clinical implications for the treatment of ischemic stroke patients. Despite recent advances, there is still insufficient data to suggest that routine genetic testing improves outcomes in patients treated with warfarin or clopidogrel for prevention of stroke.

Effect of Clopidogrel Added to Aspirin in Patients with Atrial Fibrillation

The Atrial Fibrillation Clopidogrel Trial with Irbesartan for Prevention of Vascular Events (ACTIVE) W trial showed that warfarin therapy was superior to clopidogrel plus aspirin for patients with atrial fibrillation who have at least one stroke risk factor (JW Neurol Sep 6 2006). Now, the same research group report results of the international ACTIVE A study, comparing aspirin plus placebo with aspirin plus clopidogrel for stroke prevention in patients with atrial fibrillation and at least one stroke risk factor who were considered “not suitable” for warfarin therapy. A total of 7554 patients were …