Clopidogrel Therapy In Patients Research Articles

Contribution of ticagrelor therapy in patients with acute coronary syndrome and patients with myocardial infarction to the achievement of State Program "Health Development" target in Russia as a whole and Russian regions in 2023-2025

Aim. To evaluate the contribution ticagrelor compared with clopidogrel therapy in patients with acute coronary syndrome (ACS) and patients with myocardial infarction (MI) to achieving the State Program "Health Development" target "decrease of cardiovascular mortality" in the country as a whole and Russian regions in 2023-2025.Material and methods. In the first year of therapy, all patients over 18 years of age with a confirmed diagnosis of ACS who were indicated for dual antiplatelet therapy (DAPT) were considered as the target population. In the second and third years, therapy was continued by patients at high risk of coronary events after MI. The number of deaths that could be additionally prevented within 1 year after diagnosis using DAPT with ticagrelor compared with DAPT with clopidogrel was calculated based on the PLATO trial. For post-MI patients, the number of deaths that could be prevented in the second and third years of therapy using DAPT with ticagrelor+acetylsalicylic acid (ASA) compared with ASA monotherapy was calculated based on the PEGASUS trial. The proportion of the target "decrease of cardiovascular mortality of the population" in 2023-2025 that can be achieved by using DAPT with ticagrelor instead of clopidogrel or ASA monotherapy was calculated.Results. The use of ticagrelor as part of DAPT for patients with ACS will make it possible (compared to DAPT with clopidogrel or ASA) to contribute to achieving "decrease of cardiovascular mortality" target in the Russian Federation:in 2023 — 8,0% due to expected prevention of 4443 cardiovascular deaths,in 2024 — 30,3% due to expected prevention of 4753 cardiovascular deaths,in 2025, 5366 cardiovascular deaths can be Conclusion. The use of ticagrelor as part of DAPT for patients with ACS will contribute to achieving "decrease of cardiovascular mortality" target in the Russian Federation.

Analysis of CYP2C19 gene polymorphism and influencing factors of pharmacological response of clopidogrel in patients with cerebral infarction in Zhejiang, China.

Certain genetic and non-genetic factors may cause damaged platelet inhibition by clopidogrel. We aimed to determine the effect of cytochrome P4502C19 (CYP2C19) polymorphism, along with other clinical factors, on the platelet response to clopidogrel in patients with acute ischemic stroke (AIS). A total of 214 patients with AIS receiving clopidogrel at a maintenance dose of 75 mg daily admitted to the Ningbo First Hospital between 1 January 2020, and 31 December 2021, were enrolled. Platelet aggregation analysis was performed to determine clopidogrel resistance. Quantitative real-time polymerase chain reaction (QRT-PCR) was used to determine CYP2C19 genotype. Other laboratory data on complete blood count and biochemical parameters were taken from patient medical files. Among the 214 AIS patients treated with clopidogrel in the Ningbo population, the incidence of clopidogrel resistance was approximately 43.9%, and the distribution of CYP2C19 genotypes was highest for CYP2C19(*1/*2) (43.0%), followed by CYP2C19 (*1/*1) (38.8%). The distribution of alleles *1, *2, *3, and *17 was 62.1, 32.5, 4.9, and 0.5%, respectively. A chi-squared test showed that the gene frequencies of alleles *2 and *3 were significantly higher in the clopidogrel-resistant group than in the clopidogrel-sensitive group (p < 0.001), and a Mann-Whitney U-test showed that high HCY levels were significantly correlated with clopidogrel resistance (p < 0.001). Multi-factor logistic regression analysis demonstrated that mutant heterozygous genotype [OR 2.893; 95% confidence interval (CI) 1.456-5.748; p = 0.002], mutant homozygous genotype (OR 4.741; 95% CI 1.828-12.298; p = 0.001), and high HCY levels (OR 1.209; 95% CI 1.072-1.362; p = 0.002) were significantly associated with clopidogrel resistance. According to our results, carrying the CYP2C19*2/*3 allele and high HCY levels are independent risk factors for clopidogrel resistance after clopidogrel therapy in patients with AIS. These two factors should be considered prior to clopidogrel administration.

No rebound effect after a course of clopidogrel in patients with acute TIA or minor stroke

ABSTRACT Background and Purpose Previous studies demonstrated that discontinuation of clopidogrel in patients after ACS was associated with a rebound increase in risk of recurrent events. In this study, we aimed to investigate the rebound effect after discontinuation of clopidogrel therapy in patients with TIA or stroke. Methods All patients with minor stroke or TIA were recruited from the Clopidogrel in High-Risk Patients With Acute Nondisabling Cerebrovascular Events (CHANCE) trial. Patients were divided into two groups: patients who discontinued clopidogrel and switched to aspirin therapy (Clopidogrel Discontinuation Group) and patients who continued one mono-antiplatelet therapy (non-Clopidogrel Discontinuation Group) during 90-180 days. The outcomes included risks of recurrent ischemic stroke, recurrent TIA, and composite events during 90-180 days. The prevalence of each outcome was compared between two groups for every 30 days. Further subgroup analysis was conducted in patients with and without CYP2C19 loss-of-function alleles. Results Among the 3456 patients included, a total of 10 patients in the Clopidogrel Discontinuation Group and 11 patients in the non-Clopidogrel Discontinuation Group presented ischemic stroke recurrence during the 90–180-day period. The inter-group comparisons were not significant in each 30 days. Similar results were found for recurrent stroke, recurrent TIA, and composite events in these two groups, which were also found in CYP2C19 subgroup analysis. Conclusions No rebound increase in the risk of ischemic stroke and composite events was found during the 90 days after discontinuation of clopidogrel therapy in patients with TIA or minor stroke in the CHANCE trial. Trial Registration clinicaltrials.gov Identifier: NCT00979589

Evaluation of response to clopidogrel therapy in patients with acute coronary syndrome by platelet aggregation method

Evaluation of response to clopidogrel therapy in patients with acute coronary syndrome by platelet aggregation method

Effect of polymorphism of platelet receptors genes P2RY12, ITGB3 and CYP2C19 cytochrome metabolizer enzyme on the platelet activity and efficiency of clopidogrel in patients with stable stenocardia in the Grodno region

The aim of the study was to assess the distribution of polymorphic variants G681A of the CYP2C19 gene, H1/H2 of the P2RY12 gene, and T1565C of the ITGB3 gene and to study their effect on the platelet activity and clopidogrel efficacy in patients with stable stenocardia living in the Grodno region. The study included 92 patients with stable stenocardia, 89 of them underwent elective percutaneous coronary intervention (PCI), and 93 practically healthy people. The survey data (general clinical, aggregometry, general blood count and platelet indices, and polymerase chain reaction genotyping) were analyzed using the STATISTICA 10.0 software.A high prevalence of carriage of genotypes associated with possible variability in response to clopidogrel therapy was revealed both among patients with stable stenocardia and among practically healthy individuals in the Grodno region. The frequency of occurrence of studying genotypes among patients with stable stanocardia was 23.9 % for the CYP2C19 gene (polymorphic locus G681A), 40.2 % for the P2RY12 gene (polymorphic locus H1/H2), and 31.5 % for the gene ITGB3 (polymorphic locus T1565C). For the group of practically healthy individuals, the distribution of these genotypes was 18.3; 46.2; 37.6 %, respectively. Associations were revealed between the carriage of the 681A allele of the CYP2C19 gene and the H2 haplotype of the P2RY12 gene with high residual platelet reactivity during clopidogrel therapy in patients with stable stenocardia. An association was found between the carriage of the H2 haplotype of the H1/H2 polymorphism of the P2RY12 gene with high platelet MPV values and a higher frequency of large platelets (P-LCR) in patients with stable stenocardia.

Association between CYP2C19 polymorphisms and clinical outcomes in patients undergoing stent procedure for cerebral artery stenosis

We investigated the effect of CYP2C19 polymorphisms on the clinical outcomes of clopidogrel therapy in patients after stenting procedure for cerebral artery stenosis in northeast China. 568 patients performed CYP2C19 genotype screening in the neurosurgery department of our hospital; 154 patients were finally recruited according to the inclusion and exclusion criteria, and followed-up for 6 months. Ischemic events including (1) transient ischemic attack (TIA); (2) stent thrombosis; (3) ischemic stroke; and (4) death were defined as primary clinical endpoints. The frequencies of CYP2C19*1, *2 and *3 alleles in 568 patients were 63.1%, 31.1% and 5.8%, respectively. 154 patients were classified into extensive (65 patients; 42.2%), intermediate (66 patients; 42.9%), and poor (23 patients; 14.9%) metabolizer groups. A χ2 test showed a significant difference in primary clinical endpoints at 6 months (P = 0.04), and a multivariate Cox regression analysis indicated that the CYP2C19 loss-of-function (LOF) alleles associated with post-procedure prognosis. The Kaplan–Meier curve revealed that there was no significant difference in ischemic events between *2 and *3 alleles carriers. Our study verifies that CYP2C19 *2 and *3 have significant impact on the clinical outcomes of clopidogrel therapy in patients with stenting procedure for cerebral artery stenosis in China.

Abstract TMP24: No Rebound Effect After Clopidogrel Discontinuation in Patients With Acute Transient Ischemic Attack or Minor Stroke: Subanalysis of the CHANCE Trial

Objectives: The combination of clopidogrel and aspirin was superior to aspirin alone in reducing recurrent stroke in patients with acute minor stroke or TIA. Previous studies demonstrated that discontinuation of clopidogrel in patients after ACS was associated with a rebound increase in risk of recurrent events. However, limited data investigated the rebound effect of clopidogrel after discontinuation of clopidogrel therapy in patients with TIA or stroke. Methods: All patients with minor stroke or TIA were recruited from the Clopidogrel in High-Risk Patients With Acute Nondisabling Cerebrovascular Events (CHANCE) trial. Patients who discontinued clopidogrel and switched to aspirin monotherapy during 90 days and 1 year in the clopidogrel plus aspirin arm, and patients who who continued aspirin monotherapy during 90 days and 1 year in the placebo plus aspirin arm were included to our final analysis. The outcomes included risk of recurrent ischemic stroke, recurrent TIA, and composite events during 90 days and 1 year. The prevalence of each outcome was compared between 2 groups for every 30 days. Results: Among 3346 patients included, a total of 34 patients in group who discontinued clopidogrel and switched to aspirin monotherapy presented stroke recurrence, and a total of 42 patients in group continued aspirin monotherapy presented stroke recurrence during the 90 days-1 year period. The inter-group comparisons were not significant, except during day 211 to day 240 (P=0.03). Similar results were found for recurrent ischemic stroke, recurrent TIA, and composite events in these two groups. Conclusions: we found no rebound increase in risk of stroke, ischemic stroke, TIA, and composite events during the 270 days after discontinuation of clopidogrel therapy in patients with TIA or minor stroke.

Impact of Clopidogrel Therapy on Mortality and Cancer in Patients With Cardiovascular and Cerebrovascular Disease: A Patient-Level Meta-Analysis.

Clinical trial data associate extended clopidogrel therapy with increased mortality and cancer. We sought to determine the impact of continued clopidogrel use on mortality and cancer within a patient-level meta-analysis of randomized clinical trials. Meta-analytic clinical event rates for all-cause, cardiovascular, noncardiovascular, and cancer-related mortality; cancer; myocardial infarction; stroke; and fatal and major nonfatal bleeding were generated using patient-level data from 6 randomized trials comparing prolonged versus no or short-duration clopidogrel on a background of aspirin in patients with cardiovascular and cerebrovascular disease. Among 48 817 randomized patients (median follow-up 546 days), there was no difference in all-cause (7.23% versus 7.26%; P=0.97), cardiovascular (5.25% versus 5.22%; P=0.86), noncardiovascular (1.98% versus 2.03%; P=0.73), and cancer-related (0.93% versus 0.99%; P=0.59) mortality or in new cancer diagnoses (2.97% versus 2.96%; P>0.99). Rates of myocardial infarction (3.21% versus 4.05%; P<0.0001) and stroke (3.04% versus 3.75%; P<0.0001) were significantly lower in patients receiving continued clopidogrel. Fatal bleeding was more common with continued clopidogrel use (0.39% versus 0.27%; P=0.03), as were major nonfatal bleeding (4.06% versus 2.68%; P<0.0001) and intracranial hemorrhage (0.43% versus 0.30%; P=0.02). Across trials of cardiovascular and cerebrovascular disease, extended-duration clopidogrel on a background of aspirin has no overall effect on mortality or cancer but does reduce rates of myocardial infarction and stroke and increase rates of bleeding. These findings emphasize the need for selective use of extended clopidogrel therapy in patients in whom the risks of ischemia are not fully counterbalanced by the risks of bleeding.

Liver Function is Associated With Response to Clopidogrel Therapy in Patients Undergoing Angioplasty and Stenting.

The relationship between liver function and clopidogrel response has not been studied so far. We therefore sought to investigate the associations between 3 parameters of liver synthesis and on-treatment platelet reactivity to adenosine diphosphate in patients on dual antiplatelet therapy. On-treatment platelet reactivity was determined by the VerifyNow P2Y12 assay in 316 patients undergoing angioplasty with stent implantation for cardiovascular disease. Cholinesterase, serum albumin, and total cholesterol levels were measured by internationally standardized assays in the hospital's central laboratory. On-treatment platelet reactivity by the VerifyNow P2Y12 assay correlated inversely with cholinesterase, serum albumin, and total cholesterol levels (all P ≤ .02). The inverse associations of cholinesterase and serum albumin levels with platelet reactivity remained significant after adjustment for cytochrome P450 loss-of-function polymorphisms and other factors that were previously associated with high on-treatment residual platelet reactivity (HRPR; both P < .05). Patients without HRPR by the VerifyNow P2Y12 assay had significantly higher levels of serum albumin and total cholesterol than patients with HRPR (both P = .008). In conclusion, liver function is associated with response to clopidogrel therapy in patients undergoing angioplasty and stenting for cardiovascular disease.

CYP2C19 loss-of-function alleles are not associated with clinical outcome of clopidogrel therapy in patients treated with newer-generation drug-eluting stents.

CYP2C19 loss-of-function (LOF) alleles adversely affect clinical outcome of clopidogrel therapy. Recent introduction of a newer-generation drug-eluting stent (DES) has significantly reduced the occurrence of stent thrombosis.The aim of this study was to evaluate the impact of CYP2C19 LOF alleles on clinical outcome in patients treated with the newer-generation DES.The effects of CYP2C19 genotypes were evaluated on clinical outcome of clopidogrel therapy in 2062 patients treated with percutaneous coronary intervention using either first-generation DES (sirolimus- and paclitaxel-eluting stent, n = 1349) or newer-generation DES (everolimus- and zotarolimus-eluting stent, n = 713). The primary clinical outcome was major cardiac and cerebrovascular event (MACCE) including cardiac death, nonfatal myocardial infarction, stroke, and stent thrombosis during 1 year of follow-up.CYP2C19 LOF alleles were significantly associated with a higher risk of MACCE in patients treated with first-generation DES (hazard ratio [HR] 2.599, 95% confidence interval [CI] 1.047–6.453; P = 0.034). In contrast, CYP2C19 LOF alleles were not associated with primary outcome in newer-generation DES (HR 0.716, 95% CI 0.316–1.622; P = 0.522). In the further multivariate analysis, CYP2C19 LOF alleles were not associated with MACCE in patients receiving newer-generation DES (adjusted HR 0.540, 95% CI 0.226–1.291; P = 0.166), whereas they were demonstrated to be an independent risk factor for MACCE in those implanted with first-generation DES (adjusted HR 3.501, 95% CI 1.194–10.262; P = 0.022).In contradiction to their clinical impact in first-generation DES era, CYP2C19 LOF alleles may not affect clinical outcome of clopidogrel therapy in patients treated with newer-generation DES.

Association of CYP2C19 Polymorphisms with the Clinical Efficacy of Clopidogrel Therapy in Patients Undergoing Carotid Artery Stenting in Asia.

The CYP2C19 gene plays a detrimental role in the metabolism of clopidogrel. This study aimed to investigate the association between CYP2C19 polymorphisms and the clinical efficacy of clopidogrel therapy in patients who have undergone carotid artery stenting (CAS). CYP2C19 genotype screening was performed on 959 ischemic stroke patients. Of these patients, 241 who had undergone CAS were enrolled in the study. They were all followed up for 1 year after stent surgery, and the primary clinical end-points were ischemic events. The frequencies of the CYP2C19*2 and *3 alleles among the 959 patients were 31.80% and 5.06%, respectively. Regarding the 241 participants who had undergone CAS, multivariate Cox regression analysis showed that the CYP2C19 loss-of-function (LOF) alleles (*2 and *3) were risk factors for post-CAS prognosis. Within 1 year of follow-up, the patients carrying the CYP2C19 LOF alleles were more likely to experience ischemic events than those carrying none. The occurrence of ischemic events did not significantly differ between the *2 and *3 allele carriers. Our results suggest that CYP2C19 LOF alleles (*2 and *3) significantly impact the prognosis of patients on clopidogrel therapy after CAS and that the CYP2C19*2 and CYP2C19*3 alleles have the same effects on prognosis.

Risks and Benefits of Dual Antiplatelet Therapy Beyond 12 Months After Coronary Stenting: A Prospective Randomized Cohort Study.

The optimal duration of dual antiplatelet therapy (DAT) after coronary stenting remains poorly define. The aim of this study was to evaluate the impact of longer than 24 months DAT in patients who received drug-eluting and bare-metal stents.A total of 1010 individuals who underwent elective, urgent or emergency coronary angioplasty with intended stent implantation at reference or specialized cardiac hospitals were randomized to receive long-term and short-term DAT to determine the benefits and adverse effects of long-term DAT. Total of 508 patients were randomized to long-term and 502 patients to <1 year DAT, and all of them were followed for more than 36 months for major adverse cardiac and cerebvascular events and bleeding major adverse cardiac and cerebvascular events (MACCE)Mean age of the 1010 patients (364 women and 646 men) was 60 years. Stent reocclusion occurred in 15 patients. Mean Syntax score was 23.00 ± 5.08 for whole samples, 25.00 ± 5.27 in 28 patients with MACCE and 23 ± 5.00 in 982 patients without MACCE (P = 0.057). According to all specified bleeding definitions, clopidogrel therapy for >12 months was not associated with a greater risk of hemorrhage. A regimen of >12 months of clopidogrel therapy in patients who had received drug-eluting or bare-metal stents did not differ significantly from a regimen of <12 months on clopidogrel with regard to MACCE.Long-term DAT might not significantly affect the reduction in the risk of death from any cause, myocardial infarction, or stroke, and not associated with minor or major bleeding events.

Prior chronic clopidogrel therapy is associated with increased adverse events and early stent thrombosis.

Despite the growing use of clopidogrel, limited data exist regarding the prognostic significance of chronic clopidogrel therapy in patients sustaining acute coronary syndrome (ACS). Our aim was to determine whether patients sustaining ACS while on chronic clopidogrel therapy have a worse prognosis than clopidogrel-naïve patients. A total of 5,386 consecutive ACS patients were prospectively characterised and followed-up for 30 days. Of them, 680 (13%) were treated with clopidogrel prior to the index ACS. Major adverse cardiovascular events (MACE) were defined as death, recurrent ACS, stroke and/or stent thrombosis. Compared with clopidogrel-naïve, chronic clopidogrel-treated patients were older (66 ± 12 vs 63 ± 13, respectively; p<0.01), suffered more from diabetes mellitus, hypertension, dyslipidaemia, prior cardiovascular history, including prior myocardial infarction, revascularisation, coronary artery bypass graft and stroke (p<0.01 for all), and were less likely to present with ST-elevation myocardial infarction (21% vs 45%; respectively; p < 0.001). Prior clopidogrel therapy was associated with a two-fold increase in in-hospital (1.6% vs 0.6%, respectively; p =0.006) as well as 30-day stent thrombosis (2.2% vs 1.0%, respectively; p=0.007). MACE at 30 days was also higher among chronic clopidogrel-treated compared with clopidogrel-naïve patients [12.3% vs 9.4%, respectively; p<0.01]. In multivariate log regression analysis chronic clopidogrel treatment was an independent predictor of stent thrombosis [OR=2.6 (95%CI 1.2-5.6), p=0.001]. Patients sustaining ACS while on chronic clopidogrel treatment are at higher risk for in-hospital and 30-day adverse outcomes, including stent thrombosis.

Prolonged Clopidogrel Use is Associated with Improved Clinical Outcomes Following Drug-Eluting But Not Bare Metal Stent Implantation.

Guidelines recommend clopidogrel use for 6-12 months following drug-eluting stent (DES) implantation and 1-12 months following bare metal stent (BMS) implantation. The role of clopidogrel beyond 12 months is unclear. We linked hospital administrative, community pharmacy and cardiac revascularization data to determine clopidogrel use and outcomes for all patients (those with acute presentations and those with stable angina) receiving a coronary stent in British Columbia 2004-2006, with follow-up until the end of 2008. Cox proportional hazard regression was performed to evaluate the effect of clopidogrel duration (≤12 vs. >12 months) on outcomes following BMS or DES implantation. Patients who died ≤12 months from index stent placement were excluded. A total of 15,629 patients were included in the study. Of 3599 patients who received at least one DES and 12,030 patients who received only BMS, 1326 (37 %) and 2121 (18 %), respectively, filled a prescription for clopidogrel >12 months from the index procedure. The mean duration of clopidogrel was 406 ± 35 days and 407 ± 37 days in the prolonged use (>12 months) DES and BMS cohorts, respectively, compared with 224 ± 112 days (p < 0.001) and 122 ± 117 days (p < 0.001), respectively, for patients receiving clopidogrel ≤12 months. Clopidogrel use beyond 12 months was associated with a reduction in mortality [hazard ratio (HR) 0.66, 95 % confidence interval (CI) 0.45-0.97] and the composite of mortality and readmission for myocardial infarction (HR 0.72, 95 % CI 0.55-0.94) in patients treated with DES, but not BMS alone. Prolonged clopidogrel use was not associated with bleeding-related mortality. Clopidogrel use beyond 12 months was associated with a reduction in death and hospitalization for myocardial infarction following DES, but not BMS, implantation. Our findings support a longer duration of clopidogrel therapy for patients treated with DES.

A single-centre, randomised study on platelet reactivity after abrupt or gradual discontinuation of long-term clopidogrel therapy in patients after percutaneous coronary intervention.

Clinical studies have suggested increased risk of thrombotic events after planned cessation of clopidogrel therapy, due to increased platelet reactivity (platelet rebound); however, in many studies platelet function was not assessed before introducing clopidogrel. Patients who are scheduled to stop clopidogrel therapy, do it abruptly, so a gradual drug cessation might provide a beneficial treatment strategy. To determine whether a clopidogrel discontinuation results in platelet rebound hyperaggregability with increased activity compared to pre-treatment values and to assess whether abrupt or tapering clopidogrel cessation may affect platelet reactivity. Patients with stable coronary artery disease (n = 49), on chronic acetylsalicylic acid treatment, who underwent coronary angiography, and were scheduled for elective percutaneous coronary intervention with stent implantation were en-rolled. Patients were randomised to either a tapering clopidogrel discontinuation during a two-week period (tapering group, n = 25) or abrupt drug cessation (abrupt group, n = 24). After 12 months of dual antiplatelet therapy with clopidogrel and acetylsalicylic acid, we performed three follow-up visits with blood sampling. Platelet aggregation was assessed using a mul-tiple electrode aggregometer at inclusion, at cessation day, and seven and 14 days after complete clopidogrel discontinuation. The primary endpoint was the level of adenosine-diphosphate (ADP)-induced platelet aggregation. We also analysed platelet function in the ASPI test and platelet count as secondary endpoints. In 36 patients included in the main analysis, we found significant differences between the two study groups in the levels of ADP-induced platelet aggregation at days seven and 14 after cessation of clopidogrel (p = 0.004 and p = 0.04, respectively). In the abrupt group, platelet aggregation returned to the values similar to baseline at day seven. There were no significant differences between baseline, seven, and 14 days after drug cessation (p = 0.92 and p = 0.37, respectively). However, in the tapering group, ADP values at seven and 14 days after drug cessation were significantly decreased, comparing to baseline (p < 0.0001 and p = 0.009, respectively). For the ASPI test and platelet count we did not find significant differ-ences between the groups. All values returned to levels similar to the baseline. During the follow-up there were no serious cardiovascular events or bleedings. Tapering vs. abrupt discontinuation of clopidogrel treatment results in significantly lower platelet aggregation values after 14 days from complete drug cessation. We found no evidence of a platelet rebound effect.

Changes of high sensitivity C-reactive protein during clopidogrel therapy in patients undergoing percutaneous coronary intervention

Background: The crucial role of inflammation in the development and progression of atherosclerosis has been previously described. However, there is insufficient data available to demonstrate the changes in high sensitivity C-reactive protein (hs-CRP) during clopidogrel therapy. Objectives: In the present study, we aimed to assess the changes in the inflammatory marker of coronary heart disease, i.e., hs-CRP during clopidogrel therapy, in patients undergoing percutaneous coronary intervention (PCI). We also evaluated the anti-inflammatory effects of clopidogrel, if any, in different groups of patients. Patients and Methods: The study population included 650 consecutive patients who underwent elective, urgent, or emergent PCI. Patients received a300-mg loading dose of clopidogrel (Plavix®) and aspirin either 24 hours before the planned PCI, or immediately before the procedure in patients with urgent or emergent PCI, followed by a 75-mg daily maintenance dose for up to 12 weeks. At the end of the 12th week, hs-CRP was re-assessed. Results: Six hundred-fifty patients including 386 (59.4%) male and 264 (40.6%) female subjects were enrolled in the study. The mean hs- CRP level was 15.36 ± 9.83 mg/L with a median of 14 mg/L (interquartile range 8 to 19.6 mg/L). Female, hypertensive, diabetic, and non- smoking patients had higher reductions in hs-CRP in response to clopidogrel therapy compared to male, non-hypertensive, non-diabetic and smoker patients, respectively (all P < 0.005). The changes in the hs-CRP levels were also statistically different in patients with various index events before PCI (P < 0.001). No significant differences were observed in the mean reduction of hs-CRP between the patients without stent implantation and those with bare metal or drug-eluting stents (P = 0.07), respectively. Conclusions: We found that the use of clopidogrel in patients undergoing PCI had favorable effects on the suppression of hs-CRP. This effect appears to be heightened and more apparent in some group of patients with co-morbidities such as diabetes and hypertension.

Changes of High Sensitivity C-Reactive Protein During Clopidogrel Therapy in Patients Undergoing Percutaneous Coronary Intervention

Background:The crucial role of inflammation in the development and progression of atherosclerosis has been previously described. However, there is insufficient data available to demonstrate the changes in high sensitivity C-reactive protein (hs-CRP) during clopidogrel therapy.Objectives:In the present study, we aimed to assess the changes in the inflammatory marker of coronary heart disease, i.e., hs-CRP during clopidogrel therapy, in patients undergoing percutaneous coronary intervention (PCI). We also evaluated the anti-inflammatory effects of clopidogrel, if any, in different groups of patients.Patients and Methods:The study population included 650 consecutive patients who underwent elective, urgent, or emergent PCI. Patients received a 300-mg loading dose of clopidogrel (Plavix®) and aspirin either 24 hours before the planned PCI, or immediately before the procedure in patients with urgent or emergent PCI, followed by a 75-mg daily maintenance dose for up to 12 weeks. At the end of the 12th week, hs-CRP was re-assessed.Results:Six hundred-fifty patients including 386 (59.4%) male and 264 (40.6%) female subjects were enrolled in the study. The mean hs-CRP level was 15.36 ± 9.83 mg/L with a median of 14 mg/L (interquartile range 8 to 19.6 mg/L). Female, hypertensive, diabetic, and non-smoking patients had higher reductions in hs-CRP in response to clopidogrel therapy compared to male, non-hypertensive, non-diabetic and smoker patients, respectively (all P < 0.005). The changes in the hs-CRP levels were also statistically different in patients with various index events before PCI (P < 0.001). No significant differences were observed in the mean reduction of hs-CRP between the patients without stent implantation and those with bare metal or drug-eluting stents (P = 0.07), respectively.Conclusions:We found that the use of clopidogrel in patients undergoing PCI had favorable effects on the suppression of hs-CRP. This effect appears to be heightened and more apparent in some group of patients with co-morbidities such as diabetes and hypertension.

Accumetrics-based clopidogrel dosing in endovascular neurosurgery

Introduction:The role of the VerifyNow test to guide clopidogrel therapy in neurosurgical patients is still unclear. This study compared outcomes in patients undergoing neurointerventional procedures on either standard clopidogrel or tailored clopidogrel regimens.Methods:Adult patients undergoing neurointerventional procedures from 1 May 2002 to 31 December 2012 at the University of Illinois Hospital and Health Sciences System were included if they were receiving dual antiplatelet therapy (DAPT) for their procedure. Patients were categorised based on the use of VerifyNow to guide therapy. The primary endpoint was the incidence of thromboembolic complications within 6 months post procedure. Secondary endpoints included the incidence of haemorrhagic complications and death. P2Y12 reaction units (PRU) were recorded when available and categorised based on relation to procedures and/or events.Results:A total of 228 patients were screened with 130 meeting inclusion criteria. Ninety patients were grouped into the standard therapy arm and 30 patients into the tailored therapy arm. There were no differences in the incidence of ischaemic complications (1.1 vs 2.5%, P = 0.522), haemorrhagic complications (17.8 vs 15.0%, P = 0.455) or death (3.0 vs 0%, P = 0.552). Seventeen of 32 patients (53.1%) with PRUs were clopidogrel resistant defined as a PRU >180.Discussion:Use of the VerifyNow test to guide clopidogrel therapy in patients undergoing neurointerventional procedures did not result in a decrease in the incidence of thromboembolic complications compared to standard therapy. There was no difference in the incidence of haemorrhagic complications or death. Further studies are needed to evaluate the impact of tailored therapy using VerifyNow.

Challenges in Antiplatelet Therapy Management

This article reviews the main data regarding ticagrelor, prasugrel, and clopidogrel therapy in patients with ST-segment elevation myocardial infarction (STEMI). Additional topics include new evidence regarding the timing of antiplatelet loading, managing antiplatelet therapy in patients undergoing CABG surgery, as well as new strategies for managing atrial fibrillation and concomitant coronary artery disease and acute coronary syndromes.

Effects of cytochrome P450 2C19 and paraoxonase 1 polymorphisms on antiplatelet response to clopidogrel therapy in patients with coronary artery disease.

Clopidogrel is an antiplatelet prodrug that is recommended to reduce the risk of recurrent thrombosis in coronary artery disease (CAD) patients. Paraoxonase 1 (PON1) is suggested to be a rate-limiting enzyme in the conversion of 2-oxo-clopidogrel to active thiol metabolite with inconsistent results. Here, we sought to determine the associations of CYP2C19 and PON1 gene polymorphisms with clopidogrel response and their role in ADP-induced platelet aggregation. Clopidogrel response and platelet aggregation were determined using Multiplate aggregometer in 211 patients with established CAD who received 75 mg clopidogrel and 75–325 mg aspirin daily for at least 14 days. Polymorphisms in CYP2C19 and PON1 were genotyped and tested for association with clopidogrel resistance. Linkage disequilibrium (LD) and their epistatic interaction effects on ADP-induced platelet aggregation were analysed. The prevalence of clopidogrel resistance in this population was approximately 33.2% (n = 70). The frequencies of CYP2C19*2 and *3 were significantly higher in non-responder than those in responders. After adjusting for established risk factors, CYP2C19*2 and *3 alleles independently increased the risk of clopidogrel resistance with adjusted ORs 2.94 (95%CI, 1.65–5.26; p<0.001) and 11.26 (95%CI, 2.47–51.41; p = 0.002, respectively). Patients with *2 or *3 allele and combined with smoking, diabetes and increased platelet count had markedly increased risk of clopidogrel resistance. No association was observed between PON1 Q192R and clopidogrel resistance (adjusted OR = 1.13, 95%CI, 0.70–1.82; p = 0.622). Significantly higher platelet aggregation values were found in CYP2C19*2 and *3 patients when compared with *1/*1 allele carriers (p = 1.98×10−6). For PON1 Q192R genotypes, aggregation values were similar across all genotype groups (p = 0.359). There was no evidence of gene-gene interaction or LD between CYP2C19 and PON1 polymorphisms on ADP-induced platelet aggregation. Our findings indicated that only CYP2C19*2 and *3 alleles had an influence on clopidogrel resistance. The risk of clopidogrel resistance increased further with smoking, diabetes, and increased platelet count.