Effect Of Clopidogrel Research Articles

Early Neurologic Deterioration and Efficacy of Dual Antiplatelet in Anterior Versus Posterior Circulation Stroke.

Anterior circulation stroke (ACS) differs from posterior circulation stroke (PCS) in several aspects. We hypothesize that the risk of early neurologic deterioration (END) and its responses to clopidogrel plus aspirin versus aspirin alone may be different between stroke territories. This was a prespecified post hoc analysis of ATAMIS (Antiplatelet Therapy in Acute Mild to Moderate Ischemic Stroke) trial and included patients with definite infarct location who were classified into ACS and PCS according to stroke territory. Primary outcome was occurrence of END at 7 days, defined as ≥2-point increase in National Institutes of Health Stroke Scale score compared with baseline. We compared the treatment effects of clopidogrel plus aspirin versus aspirin alone in each stroke territory. From 3000 patients, 2431 eligible patients (1780 with ACS [910 assigned into clopidogrel plus aspirin and 870 assigned into aspirin alone] and 651 with PCS [371 assigned into clopidogrel plus aspirin and 280 assigned into aspirin alone]) were included. Median age was 66 years and 35.1% were women. The occurrence of END was higher in ACS than PCS (6.8% versus 3.8%, P=0.007). clopidogrel plus aspirin was associated with lower risk of END in ACS (risk difference [95% CI]: -2.4% [-4.1% to -0.8%], P=0.004), but not in PCS (risk difference [95% CI]: -0.6% [-2.7% to 1.5%], P=0.57). No significant interaction was found (P=0.69). Our study demonstrated END was higher in acute mild-to-moderate ischemic stroke with anterior circulation, who derived more benefit from clopidogrel plus aspirin than aspirin alone. URL: https://www.clinicaltrials.gov; Unique identifier: NCT02869009.

Comparison of effectiveness of aspirin, clopidogrel and cilostazol monotherapy treatment in ischaemic stroke

Comparison of effectiveness of aspirin, clopidogrel and cilostazol monotherapy treatment in ischaemic stroke

Migratory Polyarthritis Associated With Clopidogrel: A Case Report

Clopidogrel, a selective thienopyridine, is used for secondary prevention of major adverse cardiovascular events. Some studies have reported inflammatory arthritis as a rare adverse effect of Clopidogrel. A 47-year-old male underwent percutaneous coronary intervention and was subsequently prescribed a 600 mg loading dose of Clopidogrel, followed by a daily dose of 75 mg. After six days of taking Clopidogrel, the patient presented to the emergency department with right knee pain. The knee joint exhibited swelling, warmth, and tenderness, although there was no redness or crusting. After two and six days of hospitalization, despite receiving antibiotics and Indomethacin, he developed arthritis of the metacarpophalangeal and metatarsophalangeal joints, respectively. According to the laboratory investigation, cultures, synovial fluid analysis, and imaging, infectious, rheumatologic, and crystallopathy diseases were ruled out for the patient. Clopidogrel was discontinued, and the patient was switched to ticagrelor 90 mg twice daily. All symptoms and signs of joint inflammation had improved within five days of stopping the Clopidogrel. After one week and one and six months of follow-up, there has been no recurrence of symptoms.

Comparison of effectiveness of branded and generic clopidogrel in patients with ST-elevation acute coronary syndrome on electrocardiogram

INTRODUCTION: Assessment of the effect of generic antiplatelet drugs on the outcomes of the acute coronary syndrome (ACS) still remains an unresolved issue, especially in terms of modern therapy of the disease. AIM: To assess therapeutic equivalence of the original and generic clopidogrel drug in patients with ST-elevation ACS (STE-ACS) during a three-year follow-up period. MATERIALS AND METHODS: The pilot single-center open-label retrospective-prospective observational study between 2016 and 2018 included patients with STE-ASC (n = 94; mean age 59.98 ± 7.42 years; 68.3% of men). Inclusion criteria: signed informed consent, age from 25 to 70 years; confirmed STE-ACS with performed coronary angiography and coronary angioplasty; intake of clopidogrel (branded or generic). During hospitalization for STE-ACS, all patients received branded clopidogrel at a dose of 75 mg/day, after discharge, the patients were divided into two groups: the branded clopidogrel group (Plavix®; n = 63) and the generic clopidogrel group (Zilt®, Clopidogrel®; n = 31). For 1 year, patients took clopidogrel together with acetylsalicylic acid, then continued intake of acetylsalicylic acid as monotherapy. The median follow-up was 35.5 ± 3.4 months, the study response was 100%. RESULTS: There were no statistically significant differences between the compared groups in all-cause mortality rate (overall mortality) and incidence of recurrent infarctions. At the same time, the frequency of recurrent ACS was lower in patients taking generic clopidogrel than in those taking branded clopidogrel (6.45% versus 26.98%, р 0.05). The branded clopidogrel and generic drugs were well tolerated: no cases of bleeding or adverse events associated with intake of the antiplatelet drug, were recorded. CONCLUSION: Generic clopidogrel preparations are not inferior to the branded drug in terms of efficacy and safety in patients with STE-ACS.

A comparison of the effects of ticagrelor and clopidogrel in patients with acute ST-segment elevation myocardial infarction: a systematic review and meta-analysis of randomized clinical trials

BackgroundRupture of unstable coronary atherosclerotic plaque leads to acute ST-segment elevation myocardial infarction (STEMI). Dual anti-platelet therapy is one of the main treatments, and the combination of Aspirin and Clopidogrel is recognized as the standard oral regimen in most cases. Ticagrelor is a new generation of P2Y12 receptor inhibitors. We aimed to compare the effect of Ticagrelor and Clopidogrel in the treatment of patients post-STEMI.MethodsThis study investigated Pub Med, Scopus, Google Scholar Web of Science, and Embase Cochrane Library clinical trials.gov databases. Heterogeneity between studies was assessed using the I2 index and the Q statistic. The random effects model was used to combine studies and the Funnel plot and Egger’s test were used to assess the publication bias.ResultsEleven studies were included in this meta-analysis. 5274 patients in the Ticagrelor and 5,295 patients in the Clopidogrel groups were examined. The mean age of the patients was 58.84 years (2.70) and 59.92 years (3.19) in the Ticagrelor and Clopidogrel groups, respectively. Based on the results of the meta-analysis, compared to Clopidogrel, Ticagrelor had decreased the outcomes of mortality, recurrent myocardial infarction, stroke, and Major Adverse Cardiovascular Events (MACE). However, the post-myocardial infarction bleeding according to Bleeding Academic Research Consortium (BARC) criteria and reperfusion state regarding thrombolysis in myocardial infarction (TIMI) Flow Grading system showed no differences in both groups. However, these effects were not statistically significant.ConclusionsTicagrelor decreased the chance of mortality, re-infarction, stroke, and MACE in post-STEMI patients compared to clopidogrel. But there was no difference in the chance of major bleedings (BARC ≥ 3) and improvement in TIMI grade flow between these two drugs. However, none of these findings were statistically significant, and more studies are needed to reach definitive results.

The Comparative Effectiveness of Potent P2Y12 Inhibitors Versus Clopidogrel in Patients with Acute Myocardial Infarction Undergoing PCI: National Registry Data.

Dual antiplatelet therapy (DAPT), which is essential in AMI management, combines aspirin with a P2Y12 receptor antagonist. This study compared the effectiveness of potent P2Y12 inhibitors versus clopidogrel in AMI patients treated with percutaneous coronary intervention (PCI). Methods: 65,986 AMI patients included in a nationwide prospective registry who underwent PCI and received DAPT were studied. In total, 9,014 patients received potent P2Y12 inhibitors, and 56,074 received clopidogrel. This study focused on mortality, recurrent myocardial infarction, stroke, repeat revascularization, and major adverse cardiovascular events (MACE) over seven years. The analysis utilized unadjusted models and inverse probability of treatment weighting (IPTW) to compare prognosis, and decision curve analyses were constructed to aid clinical decision making. Results: Potent P2Y12 inhibitors significantly reduced mortality risk (unadjusted hazard ratio (HR): 0.58; IPTW HR: 0.68) and MACE (unadjusted HR: 0.66; IPTW HR: 0.78). Diabetic patients showed greater benefits (HR:0.45). In patients at high bleeding risk, the mortality rate was 13% (HR: 0.87, p = 0.08). For patients aged 75-79, the HR for mortality was 0.82, whereas for those aged >80 years, it was 0.79, indicating significant mortality risk reduction. Similar trends were observed for MACE. Conclusion: This study demonstrated that potent P2Y12 inhibitors are more effective than clopidogrel in reducing mortality and MACE in patients with AMI and underscored their potential role in improving outcomes across diverse patient subgroups. The trend was consistent even during the COVID-19 pandemic. These findings highlight the need for personalized DAPT strategies, particularly for high-bleeding-risk patients, and challenge current guidelines favoring clopidogrel use in older patients.

Choosing the most effective and safest P2Y12 Inhibitor for use in >70-year-old acute coronary syndrome patients: a network meta-analysis

Abstract Background Acute coronary syndrome (ACS) represents a significant health burden, especially in elderly patients. Antiplatelet therapy forms the cornerstone of medical treatment for ACS, prasugrel and ticagrelor are preferred for their rapid action and proven efficacy. Despite their benefits, the comparative effectiveness and safety of prasugrel, ticagrelor, and clopidogrel, especially in elderly ACS patients, represents a true gap of knowledge. Aim This study aims to compare the efficacy and safety of prasugrel, ticagrelor, and clopidogrel in elderly patients with ACS, focusing on outcomes such as major adverse cardiovascular events (MACE), stroke, major or moderate bleeding, myocardial infarction (MI), all-cause mortality, cardiac mortality, revascularization, and stent thrombosis. Methods We conducted a comprehensive literature search across PubMed, Web of Science, Cochrane, Scopus, and ClinicalTrials.gov. Thirty-seven studies were included in our network meta-analysis (NMA), with data extracted on various outcomes. Data reported as relative risks (RRs) with 95% confidence intervals. Results Our NWM revealed that there is no significant difference in the incidence of MACE between prasugrel and ticagrelor or clopidogrel (RR 0.91 [0.67, 1.25] and RR 0.86 [0.64, 1.15], respectively). Stroke outcomes also showed no significant difference (RR 0.88 [0.60, 1.28] for prasugrel vs. ticagrelor; RR 0.73 [0.52, 1.02] for prasugrel vs. clopidogrel). Ticagrelor compared to clopidogrel significantly increased the risk of major or moderate bleeding (RR 1.23 [1.08, 1.39]). Significantly decreased risks of cardiac mortality were found for prasugrel and ticagrelor compared to clopidogrel (RR 0.88 [0.78, 0.98] and OR 0.81 [0.73, 0.90], respectively). Prasugrel significantly reduced the risk of revascularization compared to ticagrelor and clopidogrel (RR 0.57 [0.42, 0.78] and RR 0.75 [0.64, 0.88], respectively). For stent thrombosis, prasugrel and ticagrelor both showed significantly decreased risks compared to clopidogrel (RR 0.71 [0.55, 0.92] and RR 0.76 [0.62, 0.93], respectively). for MI, no significant difference was observed between prasugrel and ticagrelor (RR 0.88 [CI 0.64-1.20]), prasugrel and clopidogrel (RR 0.81 [0.60-1.09]), or ticagrelor and clopidogrel (RR 0.92 [CI 0.73-1.16]). Similarly, all-cause mortality rates did not significantly differ, with an RR of 0.93 [0.68-1.27] for prasugrel vs. ticagrelor, and an RR of 0.80 [0.61-1.06] for prasugrel vs. clopidogrel. Conclusion Our NMA suggests that while there are no significant differences among prasugrel, ticagrelor, and clopidogrel in reducing the risk of MACE, stroke, MI, and all-cause mortality in elderly ACS patients, ticagrelor may increase the risk of bleeding. Prasugrel and ticagrelor offer advantages in reducing cardiac mortality, revascularization, and stent thrombosis.

Comparative discontinuation and non-bleeding side effects of Clopidogrel, Prasugrel and Ticagrelor in patients with acute coronary syndromes; a Network Meta-analysis of Randomized Controlled Trials

Abstract Background P2Y12 receptor inhibitors are highly effective treatment options following ACS. However, premature discontinuation compromises their effectiveness. Although extensive literature exists, the clinical assessment of their adherence remains controversial, requiring definitive investigation. Purpose To evaluate treatment discontinuation and non-bleeding adverse effects associatedwith platelet P2Y12 receptor inhibitors in individuals post-ACS through network meta-analysis. Methods Data Sources: MEDLINE, Embase, Cochrane, and clinicaltrials.gov to May 2021 and later updated to October 2022. Study Selection and Outcomes: Reviewers identified RCTs that enrolled patients post-ACS taking Clopidogrel, Ticagrelor, and Prasugrel. Exclusions included non-ACS indications, anticoagulation therapy, observational studies, and crossover designs. The primary outcomesincludedoverall treatment discontinuation, treatment discontinuation attributed to side effects, and dyspnea. Secondary outcomes included bradycardia and atrial fibrillation. Data Extraction and Synthesis:This network meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, employing frequentist random-effects models. The GRADE (Grading of Recommendations Assessment, Development, and Evaluation) framework was utilized to assess the certainty of evidence. Results With 139,343 participants in 32 RCTs, the overall treatment discontinuation rate across all studies was 16.57% out of a total of 137,897 participants. Ticagrelor was associated with increased risk for overall treatment discontinuation compared to Clopidogrel (RR, 1.34; 95% CI, 1.19 to 1.49; P<0.0001), Prasugrel (RR, 1.23; 95% CI, 1.07 to 1.41; P=0.0031) and placebo (RR, 1,40; 95% CI, 1.19 to 1.65; P<0.0001). In compatibility to overall treatment discontinuation, Ticagrelor was associated with increased risk for treatment discontinuation due to side effects compared to Clopidogrel (RR, 1.80; 95% CI, 1.36 to 2.38; P<0.0001), Prasugrel (RR, 1.49; 95% CI, 1.06 to 2.10; P=0.0216) and placebo (RR, 1.85; 95% CI, 1.21 to 2.83; P=0.0044). Ticagrelor, Prasugrel and Clopidogrel were associated with an increased risk for dyspnea in comparison to placebo (RR, 2.86; 95% CI, 2.57 to 3.17; P<0.0001; RR, 1.61; 95% CI, 1.35 to 1.91; P<0.0001; RR, 1.60; 95% CI, 1.41 to 1.82; P<0.0001) respectively. Ticagrelor was associated with increased risk for dyspnea compared to Clopidogrel (RR, 1.78; 95% CI, 1.65 to 1.92; P<0.0001) and prasugrel (RR, 1.78; 95% CI, 1.55 to 2.05; P<0.0001). Conclusions The findings of this study suggest that Ticagrelor presents the highest risk for premature discontinuation compared to Clopidogrel and Prasugrel. Additionally, P2Y12 receptor inhibitors, in general, are notably associated with dyspnea, with Ticagrelor showing the highest risk. These results provide health professionals with valuable information for making treatment decisions in patients post-ACS.NMA netgraphsNMA of Overall treatment discontinuation

The effect of concurrent clopidogrel and omeprazole administration on clopidogrel metabolism and platelet function in healthy cats.

Some studies in humans show that the concurrent use of clopidogrel and omeprazole decreases plasma clopidogrel active metabolite (CAM) concentrations and clopidogrel antiplatelet effects. Whether this drug interaction occurs in cats is unknown. We hypothesized that administration of clopidogrel with omeprazole would decrease plasma CAM concentrations and decrease clopidogrel antiplatelet effects in healthy cats. Ten domestic cats. In this 2-sequence, 2-period, 2-treatment randomized crossover study, healthy cats were randomly assigned to receive clopidogrel only (18.75 mg PO q24h) or clopidogrel with omeprazole (1 mg/kg PO q12h) for 10 days, followed by a 2-week washout period, and then the opposite treatment for another 10 days. Blood was collected by jugular venipuncture on days 0, 5, and 10. Plasma CAM concentrations were measured using high-performance liquid chromatography-tandem mass spectrometry. Platelet function was evaluated using Plateletworks, Multiplate Analyzer, and Platelet Function Analyzer-100 (PFA-100). Multiplate Analyzer and PFA-100 detected no difference in platelet function between days or treatment groups. Plateletworks detected a significant difference (P < .001) in platelet function from day 0 to 5 and day 0 to 10 in both treatment groups but no difference between treatment groups. Plasma CAM concentrations were significantly lower on day 10 (P < .02) in cats receiving both medications versus clopidogrel only. Concurrent omeprazole and clopidogrel administration was associated with altered pharmacokinetics on day 10, but no difference in pharmacodynamics between the 2 treatment groups. The short-term use of clopidogrel and omeprazole does not seem to alter platelet function significantly.

Comparative Analysis of Ticagrelor and Clopidogrel Effects on Medication Adherence, Adverse Events, and Laboratory Parameters in Iranian Acute Coronary Syndrome Patients Post-PCI

Background: Acute coronary syndrome (ACS) remains a critical health concern, with patient outcomes significantly influenced by the selection of antiplatelet therapy post-percutaneous coronary intervention (PCI). Existing research suggests potential benefits of ticagrelor over clopidogrel in reducing cardiovascular events. However, there is limited comparative data within the Iranian population post-angiography. Objectives: This research aimed to compare laboratory findings, adherence rates, and side effects following the administration of ticagrelor and clopidogrel in ACS patients post-PCI. Methods: A case-control study was conducted to assess the impacts of antiplatelet therapy in 200 ACS patients undergoing PCI at Masih Daneshvari Hospital, Tehran, Iran. Patients were stratified into two groups, matched by age, gender, and type of cardiac disease. One group received clopidogrel, and the other received ticagrelor. Laboratory parameters, including HDL, LDL, and CRP, were evaluated at baseline and two months after treatment initiation. Additionally, adverse effects and medication adherence were assessed to evaluate the safety and efficacy of the two antiplatelet agents. Results: The study enrolled 200 ACS patients post-PCI, with 54% male and 46% female. The age range was 38 to 84 years, with a mean age of 63.07 ± 12.54 years. Of the patients, 76% had non-ST-elevation myocardial infarction (NSTEMI), while 24% had ST-elevation myocardial infarction (STEMI). Among STEMI patients, 56.25% were treated with fibrinolytics, and 43.75% underwent primary PCI. Common adverse events included dyspnea, bleeding, and gastrointestinal symptoms. Both the ticagrelor and clopidogrel groups showed reductions in LDL levels from baseline to the two-month follow-up. Conclusions: Ticagrelor and clopidogrel were both effective in reducing LDL levels after two months of treatment. However, ticagrelor demonstrated a more pronounced decrease in CRP levels, indicating potential anti-inflammatory benefits. These findings provide insight into antiplatelet therapy's role in managing ACS patients post-PCI.

Clopidogrel Versus Aspirin as Chronic Maintenance Antiplatelet Monotherapy in Patients After Percutaneous Coronary Intervention With Chronic Kidney Disease: A Post Hoc Analysis of the HOST-EXAM Trial.

Clopidogrel monotherapy improved clinical outcomes compared with aspirin monotherapy during a chronic maintenance period in patients who underwent coronary stenting in the HOST-EXAM (Harmonizing Optimal Strategy for Treatment of Coronary Artery Stenosis-Extended Antiplatelet Monotherapy) trial. However, it is uncertain whether the beneficial effect of clopidogrel over aspirin is different according to the renal function. We conducted a post hoc analysis of the HOST-EXAM trial. Chronic kidney disease (CKD) was defined as baseline estimated glomerular filtration rate <60 mL/min per 1.73 m2. The primary end point was a composite of all-cause death, nonfatal myocardial infarction, stroke, readmission due to acute coronary syndrome, and Bleeding Academic Research Consortium bleeding type ≥3, during the 2-year follow up. Among the 5438 patients enrolled in the HOST-EXAM trial, 4844 patients (mean age, 63.3±10.6 years; 74.9% men) with a baseline creatinine value were analyzed in this study. A total of 508 (10.5%) patients had CKD, who were at higher risk of the primary end point compared with those without CKD (hazard ratio [HR], 2.01 [95% CI, 1.51-2.67]). Clopidogrel monotherapy was associated with a lower rate of the primary end point in both patients with CKD (HR, 0.74 [95% CI, 0.44-1.25]) and patients without CKD (HR, 0.71 [95% CI, 0.56-0.91]). No significant interaction was observed between the treatment effect and CKD status (P for interaction=0.889). During the chronic maintenance period after coronary stenting, the risk of thrombotic and bleeding events was significantly higher in patients with CKD compared with those without CKD. There was no statistical difference in the treatment effect of clopidogrel monotherapy in those with versus without CKD.

Clopidogrel Versus Aspirin as Monotherapy Following Dual Antiplatelet Therapy in Patients With Acute Coronary Syndrome Receiving a Drug-Eluting Stent: A Systematic Literature Review and Meta-Analysis.

This study aimed to evaluate the comparative effectiveness and safety of clopidogrel versus aspirin as monotherapy following adequate dual antiplatelet therapy (DAPT) in patients with acute coronary syndrome (ACS). MEDLINE, Embase, and CENTRAL were searched from database inception to September 1, 2023. Randomized controlled trials (RCTs) and observational studies evaluating the effectiveness or safety of clopidogrel versus aspirin as monotherapy following DAPT in patients with ACS who received a drug-eluting stent were included. Random-effects meta-analyses were conducted to compare risks of major adverse cardiovascular events (MACE) and clinically relevant bleeding. Of 6242 abstracts identified, three unique studies were included: one RCT and two retrospective cohort studies. Studies included a total of 7081 post-percutaneous coronary intervention ACS patients, 4260 of whom received aspirin monotherapy and 2821 received clopidogrel monotherapy. Studies included variable proportions of patients with ST-elevation myocardial infarction (STEMI), non-STEMI, and unstable angina. From the meta-analysis, clopidogrel was associated with a 28% reduction in the risk of MACE compared with aspirin (hazard ratio [HR]: 0.72; 95% confidence interval [CI]: 0.54, 0.98), with no significant difference in clinically relevant bleeding (HR: 0.92; 95% CI: 0.68, 1.24). Despite the paucity of published evidence on the effectiveness and safety of clopidogrel versus aspirin in patients with ACS post-drug-eluting stent implantation, this meta-analysis suggests that clopidogrel versus aspirin may result in a lower risk of MACE, with a similar risk of major bleeding. The present results are hypothesis-generating and further large RCTs comparing antiplatelet monotherapy options in ACS patients are warranted.

Impact of proton pump inhibitor use on clinical outcomes in East Asian patients receiving clopidogrel following drug-eluting stent implantation

BackgroundConcomitant use of clopidogrel and proton pump inhibitor (PPI) is common, but PPI may reduce the antiplatelet effects of clopidogrel in patients undergoing percutaneous coronary intervention (PCI). We evaluated the impact of PPI use on clinical outcomes in post-PCI patients, by incorporating P2Y12 reaction unit (PRU) and CYP2C19 genotyping results.MethodsFrom a multicenter registry of patients who underwent PCI with drug-eluting stent implantation and received clopidogrel-based dual antiplatelet therapy (DAPT), patients who were prescribed a PPI at the time of PCI (PPI users) were compared to those who were not (non-users). The primary outcome included all-cause death, myocardial infarction, stent thrombosis, or cerebrovascular accident at 12 months. Major bleeding (Bleeding Academic Research Consortium [BARC] types 3–5) and gastrointestinal (GI) bleeding (BARC types 3–5) were important secondary outcomes. The adjusted outcomes were compared using a 1:1 propensity-score (PS) matching and competing risk analysis.ResultsOf 13,160 patients, 2,235 (17.0%) were prescribed PPI, with an average age of 65.4 years. PPI users had higher on-treatment PRU levels than non-users. After PS matching, the primary outcome occurred in 51 patients who were PPI users (cumulative incidence, 4.7%) and 41 patients who were non-users (cumulative incidence, 3.7%; log-rank p = 0.27). In carriers of both CYP2C19 loss-of-function alleles, PPI use was linked to an increased risk of the primary outcome (hazard ratio, 3.22; 95% confidence interval, 1.18–8.78). The incidence of major bleeding and GI bleeding (BARC types 3–5) was comparable between PPI users and non-users in the PS-matched cohort.ConclusionsIn post-PCI patients receiving clopidogrel-based DAPT, PPI use was not linked to an increased risk of adverse cardiac and cerebrovascular events, but there was a small but significant increase in on-treatment PRU. Future research using a more individualized approach would further elucidate these interactions and guide evidence-based clinical practices.

Precision Antiplatelet Therapy after Percutaneous Coronary Intervention (Precision PCI) Registry - Informing optimal antiplatelet strategies.

Dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 receptor inhibitor (clopidogrel, prasugrel, or ticagrelor) is indicated after percutaneous coronary intervention (PCI) to reduce the risk of atherothrombotic events. Approximately 30% of the US population has a CYP2C19 no-function allele that reduces the effectiveness of clopidogrel, but not prasugrel or ticagrelor, after PCI. We have shown improved outcomes with the integration of CYP2C19 genotyping into clinical care to guide the selection of prasugrel or ticagrelor in CYP2C19 no-function allele carriers. However, the influence of patient-specific demographic, clinical, and other genetic factors on outcomes with genotype-guided DAPT has not been defined. In addition, the impact of genotype-guided de-escalation from prasugrel or ticagrelor to clopidogrel in patients without a CYP2C19 no-function allele has not been investigated in a diverse, real-world clinical setting. The Precision Antiplatelet Therapy after Percutaneous Coronary Intervention (Precision PCI) Registry is a multicenter US registry of patients who underwent PCI and clinical CYP2C19 testing. The registry is enrolling a diverse population, assessing atherothrombotic and bleeding events over 12 months, collecting DNA samples, and conducting platelet function testing in a subset of patients. The registry aims to define the influence of African ancestry and other patient-specific factors on clinical outcomes with CYP2C19-guided DAPT, evaluate the safety and effectiveness of CYP2C19-guided DAPT de-escalation following PCI in a real-world setting, and identify additional genetic influences of clopidogrel response after PCI, with the ultimate goal of establishing optimal strategies for individualized antiplatelet therapy that improves outcomes in a diverse, real-world population.

The effects of CYP2B6 inactivators on the metabolism of ciprofol.

Ciprofol is a novel short-acting intravenous anaesthetic developed in China that is mainly metabolized by cytochrome P450 2B6 (CYP2B6) and uridine diphosphate glucuronosyltransferase 1A9 (UGT1A9). Currently, insufficient evidence is available to support drug‒drug interactions between ciprofol and CYP2B6 inactivators. Here, we established a high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method to assess the concentration of ciprofol and investigated the effects of psoralen and clopidogrel on the metabolism of ciprofol in liver microsomes and rats. In rat and human liver microsomes, the median inhibitory concentration (IC50) values of psoralen were 63.31 μmol·L-1 and 34.05 μmol·L-1, respectively, showing mild inhibitory effects on ciprofol metabolism, whereas the IC50 values of clopidogrel were 6.380 μmol·L-1 and 2.565 μmol·L-1, respectively, with moderate inhibitory effects. SD rats were randomly divided into three groups: psoralen (27 mg·kg-1), clopidogrel (7.5 mg·kg-1), and the same volume of 0.5% carboxy methyl cellulose. After 7 days, all rats were injected with 2.4 mg·kg-1 ciprofol. Compared with the control group, the AUC and MRT values of ciprofol in the psoralen and clopidogrel groups were significantly greater, whereas the CL values were significantly lower. In addition, the durations of loss of righting reflex (LORR) in the psoralen and clopidogrel groups were 16.1% and 23.0% longer than that in the control group, respectively. In conclusion, psoralen and clopidogrel inhibit ciprofol metabolism to different degrees and prolong the duration of LORR in rats.

Effect of Preoperative Clopidogrel on Outcomes of Isolated Coronary Artery Bypass Graft: An STS National Database Analysis

BackgroundWe analyzed The Society of Thoracic Surgeons Database to investigate risks and optimal timing for coronary artery bypass grafting (CABG) after clopidogrel administration. MethodsPatients were categorized based on clopidogrel use within 5 days and further stratified by days from the last dose (0 to 5 days). Controls were patients who did not receive clopidogrel within 5 days of surgery. The primary outcome was operative mortality, and secondary outcomes included mediastinal reexploration for bleeding and blood product use. ResultsAmong 148,317 isolated CABG, 19,553 patients (13.2%) received clopidogrel within 5 days. Minimal differences in operative mortality (2.8% vs 2.1%, P < .001), but higher rates of mediastinal reexploration (3.5% vs 2.1%, P < .001) and blood product utilization (72.7% vs 56.8%, P < .001) were observed in the clopidogrel group. The adjusted odds ratio of operative mortality peaked on the day of clopidogrel administration but was comparable to controls thereafter. The odds of reexploration were highest on day 0, decreasing gradually to a plateau after day 3. Patients who underwent operations on day 3 after clopidogrel administration had similar odds of operative mortality and mediastinal reexploration for bleeding and shorter total and preoperative lengths of stay but higher blood product use compared with day 5. ConclusionsCABG within 5 days from clopidogrel is associated with a modest increase in operative mortality and reexploration for bleeding and a substantial increase in blood product use. Risks decreased with increasing time from discontinuation, plateauing after 3 days from clopidogrel. CABG at 3 days yields comparable outcomes as 5 days, reducing the waiting period.

Evaluating the Effect of Estimating Renal Function With the CKD-EPI 2021 Equation on the ABCD-GENE Score for Clopidogrel Response Prediction.

The ABCD-GENE score was developed to predict poor response to clopidogrel and includes Age, Body mass index, Chronic kidney disease (CKD; estimated glomerular filtration rate [eGFR] < 60 mL/min/1.73 m2), Diabetes, and CYP2C19 GENE variants; a score ≥ 10 is predictive of reduced clopidogrel effectiveness after percutaneous coronary intervention (PCI). Estimation of GFR without a race variable via the CKD-EPI Scr 2021 equation is now recommended. We examined the impact of using the CKD-EPI Scr 2021 vs. 2009 equation on the ABCD-GENE score for post-PCI patients. A total of 4335 adult patients (n = 925 Black) who underwent PCI and CYP2C19 genotyping were included, with GFR estimated for each patient via the CKD-EPI Scr 2021 and CKD-EPI 2009 equations. The ABCD-GENE score, calculated based on each GFR estimation, was compared. With the CKD-EPI Scr 2021 vs. 2009 equation, median (IQR) eGFR was lower (74 [55-94] vs. 81 [60-103] mL/min/1.73 m2, P < 0.001), and CKD prevalence was higher (31% vs. 25%, P < 0.001) among Black patients, whereas eGFR was higher (85 [65-99] vs. 80 [61-94] mL/min/1.73m2, P < 0.001), and CKD prevalence was lower (20% vs. 24%, P < 0.001) in non-Black patients. This led to 12 (1%) Black patients being reclassified from low to high risk of poor clopidogrel response and 30 (1%) non-Black patients being recategorized from high to low risk (P < 0.001 for both comparisons). Removal of the race variable from GFR estimation significantly impacted the prediction of clopidogrel effectiveness via the ABCD-GENE score.

Differential effects of clopidogrel and/or aspirin on the healing of tooth extraction wound bone tissue.

A multitude of variables influence the healing of tooth extraction wounds, and delayed or non-healing extraction wounds might complicate later prosthodontic therapy. In this research, we analyzed the effects of systemic clopidogrel and aspirin alone or in combination on the healing of tooth extraction wounds in mice in order to provide experimental evidence for the healing of extraction wounds in patients who are clinically treated with the two medicines. 7-week-old ICR mice were randomly divided into four groups: control group (CON), clopidogrel group (CLOP), aspirin group (ASP), and clopidogrel combined with aspirin group (CLOP + ASP); left upper first molar was extracted, after which mice in 1week of adaptive feeding, CLOP/ASP/CLOP + ASP groups were respectively administered with clopidogrel (10mg/kg/d), aspirin (15mg/kg/d), clopidogrel (10mg/kg/d)+aspirin (15mg/kg/d), and the control group was given an equal amount of 0.9% saline by gavage. Mice in each group were euthanized at 14 and 28days postoperatively, and the maxilla was extracted. The tissues in the extraction sockets were examined using MicroCT and sectioned for HE staining, Masson staining, and TRAP staining, and immunohistochemistry staining (for TRAP, RANKL and osteoprotegerin). MicroCT analysis showed that at day 14, BS/BV was significantly lower in CLOP and CLOP + ASP groups compared to control and ASP groups, while BV/TV, Tb.Th was significantly higher. At day 28, BV/TV was significantly higher in the CLOP + ASP group compared to the CLOP group, with p < 0.05 for all results. HE staining and Masson trichrome staining findings revealed that at day 28, the mesenchyme in the bone was further decreased compared to that at day 14, accompanied with tightly arranged and interconnected bone trabeculae. In the quantitative analysis of Masson, the fraction of newly formed collagen was significantly higher in the CLOP group in comparison with that in the CON group (p < 0.05). At day 14, the ASP group had substantially more TRAP-positive cells than the CLOP and CLOP + ASP groups (p < 0.05). In immunohistochemical staining, RANKL expression was found to be significantly higher in the ASP group than those in the other three groups at day 28 (p < 0.05); OPG expression was significantly higher in the CLOP group and the CLOP + ASP group compared with that at day 14, and was higher than that in the ASP group at day 14 and day 28. OPG/RANKL was significantly higher in the CLOP and the CLOP + ASP groups than in the ASP group (p < 0.05). Clopidogrel alone promotes osteogenesis in the extraction wound, whereas aspirin alone inhibits alveolar bone healing. When the two drugs were combined, the healing effect of the extraction wound was more similar to that of the clopidogrel alone group. These results indicated that clopidogrel could promote the healing of the tooth extraction wound, and neutralize the adverse effect of ASP on osteogenesis when the two drugs were used in combination.

Clinical Outcomes of Aspirin and Clopidogrel among Patients with Chronic Obstructive Lung Disease: Insights from a Meta-Analysis.

(1) Background: Aspirin and clopidogrel have been found helpful in improving clinical outcomes among patients with chronic obstructive lung disease (COPD). However, the evidence on the efficacy of aspirin and/or clopidogrel on clinical outcomes has not been synthesized and summarized in the prior reviews. Hence, we undertook a meta-analysis of the research studies examining the effect of aspirin and/or clopidogrel on varying clinical outcomes among COPD patients; (2) Methods: Using key search terms, we searched databases, including MEDLINE, CINAHL, Google Scholar, and EMBASE to find observational studies and RCTs. Our search was limited to research written in English. We used a random effect model to calculate the 95% confidence intervals and pooled hazard ratio; (3) Results: We included 12 eligible research studies (33,8008 patients) in the current meta-analysis. Among COPD patients, the hazard of all-cause mortality among users of aspirin or clopidogrel was 17% lower (HR: 0.83; 95% CIs (0.70, 0.97; I2 = 73%, X2: 33.34) compared to non-users of anticoagulants (aspirin or clopidogrel). The hazard of dyspnea among users of aspirin or clopidogrel was 3% lower (HR: 0.97; 95% CIs (0.27, 3.49; I2 = 93%, X2: 42.15) compared to non-users of anticoagulants (aspirin or clopidogrel). There was no statistically significant effect of aspirin on other clinical outcomes such as myocardial infarction (HR: 2.04; 95% CIs (0.02, 257.33) and major bleeding (HR: 1.93; 95% CIs (0.07, 1002.33). The funnel plot and Egger's regression test did not show any evidence of publication bias; (4) Conclusions: Overall, we found a positive and beneficial effect of aspirin and/or clopidogrel in reducing all-cause mortality among COPD patients. However, there is uncertainty of evidence for other clinical outcomes such as exacerbation of dyspnea, myocardial infarction, and major bleeding. A limited number of studies examining other clinical outcomes warrant conducting more robust epidemiological studies to assess the efficacy and safety of aspirin and clopidogrel on other clinical outcomes among COPD patients.

Analysis of the effect of CYP2C19 gene properties on the anti-platelet aggregation of clopidogrel after carotid artery stenting under network pharmacology

Antiplatelet therapy is an important factor influencing the postterm patency rate of carotid artery stenting (CAS). Clopidogrel is a platelet aggregation inhibitor mediated by the adenosine diphosphate receptor and is affected by CYP2C19 gene polymorphisms in vivo. When the CYP2C19 gene has a nonfunctional mutation, the activity of the encoded enzyme will be weakened or lost, which directly affects the metabolism of clopidogrel and ultimately weakens its antiplatelet aggregation ability. Therefore, based on network pharmacology, analyzing the influence of CYP2C19 gene polymorphisms on the antiplatelet therapeutic effect of clopidogrel after CAS is highly important for the formulation of individualized clinical drug regimens. The effect of the CYP2C19 gene polymorphism on the antiplatelet aggregation of clopidogrel after CAS was analyzed based on network pharmacology. A total of 100 patients with ischemic cerebrovascular disease who were confirmed by the neurology department and required CAS treatment were studied. CYP2C19 genotyping was performed on all patients via a gene chip. All patients were classified into the wild-type (WT) group (*1/*1), heterozygous mutation (HTM) group (CYP2C19*1/*2, CYP2C19*1/*3), and homozygous mutation (HMM) group (CYP2C19*2/*2, CYP2C19*2/*3, and CYP2C19*3/*3). High-performance liquid chromatography (HPLC) with tandem mass spectrometry (MS/MS) was used to detect the blood concentration of clopidogrel and the plasma clopidogrel clearance (CL) rate in different groups of patients before and after clopidogrel treatment. The platelet aggregation rate of patients with different genotypes was measured by turbidimetry. The incidences of clopidogrel resistance (CR) and stent thrombosis in different groups after three months of treatment were analyzed. The results showed that among the different CYP2C19 genotypes, patients from the HTM group accounted for the most patients, while patients from the HTM group accounted for the least patients. Similarly, the clopidogrel CL of patients in the HMM group was lower than that of patients in the WT group and HTM group (P < 0.01). The platelet inhibition rate of patients in the HMM group was evidently inferior to that of patients in the WT group and HTM group (P < 0.01). The incidence of CR and stent thrombosis in the WT group was notably lower than that in the HTM and HMM groups (P < 0.01). These results indicate that the CYP2C19 gene can affect CR occurrence and stent thrombosis after CAS by influencing clopidogrel metabolism and platelet count.