Abstract 13180: Impact of Cigarette Smoking on Levels on Platelet P2Y12 Mediated Platelet Inhibition in Prasugrel Treated Patients: Results of a Pharmacodynamic Study

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Fabiana Rollini ◽  
Francesco Franchi ◽  
Elisabetta Ferrante ◽  
Jung Rae Cho ◽  
Elizabeth C Dunn ◽  
...  
Keyword(s):  
Cigarette Smoking ◽  
Platelet Reactivity ◽  
Smoking Status ◽  
Objective Assessment ◽  
Serum Levels ◽  
Adverse Outcomes ◽  
Reactivity Index ◽  
Clinical Effects ◽  
Coronary Syndrome ◽  
The Impact

Introduction: In patients with established vascular disease, smoking is a strong independent risk factor for adverse outcomes, including mortality. Several investigations have shown that cigarette smoking induces cytochrome P450 enzymatic activity which in turn increases clopidogrel metabolism leading to enhanced pharmacodynamic (PD) effects compared with non-smokers. These findings may explain the heightened clinical benefits of clopidogrel in smokers compared with nonsmokers. Prasugrel has superior PD and clinical effects compared with clopidogrel. The aim of this study was to evaluate the impact of cigarette smoking on platelet P2Y 12 mediated effects among patients on maintenance prasugrel therapy. Methods: A total of 156 patients on maintenance prasugrel therapy (10mg/qd) for at least 7-days, in addition to aspirin (81mg/qd), who previously underwent a percutaneous coronary intervention in the setting of an acute coronary syndrome were studied. An objective assessment of smoking status was performed by measuring serum levels of cotinine (the major stable degradation product of nicotine metabolite). Cotinine levels >3 ng/ml identified patients as smokers. PD assessments to determine platelet P2Y 12 activity was performed by flow cytometric assessment of vasodilator-stimulated phosphoprotein (VASP). Results were reported as platelet reactivity index (PRI). A PRI>50% identified patients with high on-treatment platelet reactivity (HPR). Results: According to cotinine serum levels, patients were divided into smokers (n=55) and nonsmokers (n=101). PRI values in the overall population were not normally distributed (median [interquartile range (IQR)] 30 [19.1-38.9]) and 14.6% of patients had HPR. PRI levels were not significantly different between smokers and nonsmokers (33.7 [13.6-46.9] vs 28.8 [21.7-37.3], p= 0.56). There was no correlation between PRI values and cotinine levels (r=0.03; p=0.74). Accordingly, HPR rates were similar between smokers and nonsmokers (18.2% vs 12.9%; p=0.25). Conclusions: In patients on maintenance prasugrel therapy, cigarette smoking status, as objectively assessed by serum levels of cotinine, does not affect the degree of platelet P2Y 12 mediated inhibition.

Enhanced active metabolite generation and platelet inhibition with prasugrel compared to clopidogrel regardless of genotype in thienopyridine metabolic pathways

2013 ◽  
Vol 110 (12) ◽  
pp. 1223-1231 ◽  
Author(s):  
Dominick J. Angiolillo ◽  
Jose L. Ferreiro ◽  
Joseph A. Jakubowski ◽  
Kenneth J. Winters ◽  
Mark B. Effron ◽  
...  
Keyword(s):  
Genetic Variants ◽  
Active Metabolite ◽  
Platelet Reactivity ◽  
Coronary Intervention ◽  
Platelet Inhibition ◽  
Reactivity Index ◽  
Coronary Syndrome ◽  
Metabolite Generation ◽  
Artery Disease ◽  
The Impact

SummaryClopidogrel response varies according to the presence of genetic polymorphisms. The CYP2C19*2 allele has been associated with impaired response; conflicting results have been reported for CYP2C19*17, ABCB1, and PON1 genotypes. We assessed the impact of CYP2C19, PON1, and ABCB1 polymorphisms on clopidogrel and prasugrel pharmacodynamic (PD) and pharmacokinetic (PK) parameters. Aspirin-treated patients (N=194) with coronary artery disease from two independent, prospective, randomised, multi-centre studies comparing clopidogrel (75 mg) and prasugrel (10 mg) were genotyped and classified by predicted CYP2C19 metaboliser phenotype (ultra metabolisers [UM] = *17 carriers; extensive metabolisers [EM] = *1/1 homozygotes; reduced metabolisers [RM] = *2 carriers). ABCB1 T/T and C/T polymorphisms and PON1 A/A, A/G and G/G polymorphisms were also genotyped. PD parameters were assessed using VerifyNow® P2Y12 and vasodilator stimulated phosphoprotein (VASP) expressed as platelet reactivity index (PRI) after 14 days of maintenance dosing. Clopidogrel and prasugrel active metabolite (AM) exposure was calculated in a cohort of 96 patients. For clopidogrel, genetic variants in CYP2C19, but not ABCB1 or PON1, affected PK and PD. For prasugrel, none of the measured genetic variants affected PK or PD. Compared with clopidogrel, platelet inhibition with prasugrel was greater even in the CYP2C19 UM phenotype. Prasugrel generated more AM and achieved greater platelet inhibition than clopidogrel irrespective of CYP2C19, ABCB1, and PON1 polymorphisms. The lack of effect from genetic variants on prasugrel AM generation or antiplatelet activity is consistent with previous studies in healthy volunteers and is consistent with improved efficacy in acute coronary syndrome patients managed with percutaneous coronary intervention.

Primary care physician services and the frequency of comorbidities in patients with acute myocardial infarction

2021 ◽  
Vol 28 (Supplement_1) ◽  
Author(s):  
R King ◽  
D Giedrimiene
Keyword(s):  
Myocardial Infarction ◽  
Primary Care ◽  
Acute Myocardial Infarction ◽  
Primary Care Physician ◽  
Care Physician ◽  
Adverse Outcomes ◽  
Coronary Syndrome ◽  
Number Of Patients ◽  
Significant Difference ◽  
The Impact

Abstract Funding Acknowledgements Type of funding sources: None. Background The management of patients with multiple comorbidities represents a significant burden on healthcare each year. Despite requiring regular medical care to treat chronic conditions, a large number of these patients may not receive proper care. Significant disparities have been identified in patients with multiple comorbidities and those who experience acute coronary syndrome or acute myocardial infarction (AMI). Only limited data exists to identify the impact of comorbidities and utilization of primary care physician (PCP) services on the development of adverse outcomes, such as AMI. Purpose The primary objective was to analyze how PCP services utilization can be associated with comorbidities in patients who experienced an AMI. Methods This study was based on retrospective data analysis which included 250 patients admitted to the Hartford Hospital Emergency Department (ED) for an AMI. Out of these, 27 patients were excluded due to missing documentation. Collected data included age, gender, medications and recorded comorbidities, such as hypertension, hyperlipidemia, diabetes mellitus (DM), chronic kidney disease (CKD) and previous arrhythmia. Each patient was assessed regarding utilization of PCP services. Statistical analysis was performed in order to identify differences between patients with documented PCP services and those without by using the Chi-square test. Results The records allowed for identification of documented PCP services for 172 out of 223 (77.1%) patients. The most common comorbidities were hypertension and hyperlipidemia: in 165 (74.0%) and 157 (70.4%) cases respectively. The most frequent comorbidity was hypertension: 137 out of 172 (79.7%) in pts with PCP vs 28 out of 51 (54.9%) without PCP, and significantly more often in patients with PCP, p< 0.001. Hyperlipidemia was the second most frequent comorbidity: in 130 out of 172 (75.6%) vs 27 out of 51 (52.9%) accordingly, and also significantly more often (p< 0.002) in patients with PCP services. The number of comorbidities ranged from 0-5, including 32 (14.3%) patients without comorbidities: 16 (9.3%) with a PCP and 16 (31.4%) without PCP services. The majority of patients - 108 (48.5% of 223), had 2-3 documented comorbidities: 89 (51.8%) had two and 19 (34.6%) had three. The remaining 40 (17.9%) patients had 4-5 comorbidities: 37 (21.5%) of them with a PCP and 3 (10.3%) without, with a significant difference (p < 0.001) found for patients with a higher number of comorbidities who utilized PCP services. Conclusions Our study shows that the majority of patients who presented with an AMI had one or more comorbidities. Furthermore, patients who did not utilize PCP services had fewer identified comorbidities. This suggests that there may be a significant number of patients who experienced AMI with undiagnosed comorbidities due to not having access to PCP services.

scholarly journals Systemic Inflammatory Responses in Children with Acute Otitis Media Due to Streptococcus pneumoniae and the Impact of Treatment with Clarithromycin

2003 ◽  
Vol 10 (4) ◽  
pp. 721-724 ◽  
Author(s):  
Gunter Scharer ◽  
Frank Zaldivar ◽  
Guillermo Gonzalez ◽  
Ofelia Vargas-Shiraishi ◽  
Jasjit Singh ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Otitis Media ◽  
Antibiotic Treatment ◽  
Statistical Significance ◽  
Objective Assessment ◽  
Acute Otitis Media ◽  
Serum Levels ◽  
Asymptomatic Children ◽  
Tnf Α ◽  
The Impact

ABSTRACT This pilot study was designed to determine the serum cytokine profile of acute otitis media (AOM) due to Streptococcus pneumoniae and the impact of clarithromycin (Abbott Laboratories, Inc). Serum levels of interleukin-1β (IL-1β), tumor necrosis factor alpha (TNF-α), IL-6, and IL-8 were measured at diagnosis and 3 to 5 days after start of antibiotic treatment in 10 patients (mean age, 18.3 ± 13.9 months) who had middle ear fluid culture positive for S. pneumoniae. The mean concentrations of all cytokines were elevated at diagnosis of AOM compared to levels in healthy controls, yet only IL-6 reached statistical significance (P = 0.05). IL-6 showed a statistically significant decrease in mean serum concentration at visit 2 (P = 0.03). IL-8 displayed a similar pattern to IL-6, but the difference between samples from day 1 and day 2 did not reach statistical significance. The cytokines IL-1β and TNF-α appear to be elevated in the serum of patients with S. pneumoniae AOM, but there was no significant change between mean serum levels obtained pre- and postinitiation of antibiotic treatment in the time frame studied. The results suggest a systemic inflammatory response as evidenced by increased IL-6. A significant decrease of IL-6 and improvement of clinical symptoms were observed. Determining cytokine levels, especially IL-6, in AOM could offer a powerful tool for objective assessment of response to treatment, minimizing unnecessary treatment of asymptomatic children who may still have some otoscopic findings suggestive of AOM at follow-up visits.

Comparison of methods to evaluate clopidogrel-mediated platelet inhibition after percutaneous intervention with stent implantation

2009 ◽  
Vol 101 (02) ◽  
pp. 333-339 ◽  
Author(s):  
Sabine Steiner ◽  
Daniela Seidinger ◽  
Renate Koppensteiner ◽  
Thomas Gremmel ◽  
Simon Panzer ◽  
...  
Keyword(s):  
Stent Implantation ◽  
Light Transmission ◽  
Platelet Reactivity ◽  
Platelet Inhibition ◽  
Percutaneous Intervention ◽  
Adverse Outcomes ◽  
Gold Standard Method ◽  
Platelet Aggregometry ◽  
Increased Risk ◽  
The Impact

SummaryA high on-treatment residual ADP-inducible platelet reactivity in light transmission aggregometry (LTA) has been associated with an increased risk of adverse outcomes after percutaneous coronary intervention (PCI). However, LTA is weakly standardized, and results obtained in one laboratory may not be comparable to those obtained in another one. We therefore sought to determine the test correlating best with LTA to estimate clopidogrel-mediated platelet inhibition in 80 patients on dual antiplatelet therapy after elective percutaneous intervention with stent implantation. We selected the VerifyNow P2Y12 assay, the vasodilator-stimulated phosphoprotein phosphorylation assay, multiple electrode platelet aggregometry and the Impact-R for comparisons with LTA. Cut-off values for residual ADP-inducible platelet reactivity were defined according to quartiles of each assay. Sensitivities and specificities of the different platelet function tests were based on the results from LTA. The results from all four assays correlated significantly with those from LTA. The VerifyNow P2Y12 assay revealed the strongest correlation (r = 0.61, p < 0.001). Sensitivities and specificities ranged from 35% to 55%, and from 78.3% to 85%, respectively. In conclusion, although all assays correlated significantly with LTA, they need to be improved to become clinically used diagnostic tests. Further, it may be too early to define the gold standard method for assessing residual ADP-inducible platelet reactivity and generally acceptable cut-off values.

scholarly journals The Recalled Age of Initiation of Multiple Tobacco Products among 26–34 Year Olds: Findings from the Population Assessment of Tobacco and Health (PATH) Study Wave 1 (2013–2014)

2020 ◽  
Vol 17 (23) ◽  
pp. 9000
Author(s):  
Adriana Pérez ◽  
Elena Penedo ◽  
Meagan A. Bluestein ◽  
Baojiang Chen ◽  
Cheryl L. Perry ◽  
...  
Keyword(s):  
Cigarette Smoking ◽  
Smokeless Tobacco ◽  
Smoking Status ◽  
Tobacco Product ◽  
Tobacco Products ◽  
Replication Method ◽  
Cox Proportional Hazard Models ◽  
Secondary Analyses ◽  
Race Ethnicity ◽  
The Impact

This study examined the recalled age of initiation of seven different tobacco products (TPs) and explored potential influences of sex, race/ethnicity, and cigarette-smoking status on tobacco use initiation among adults 26–34 years old using the PATH study. Methods: Secondary analyses were conducted in the adult restricted PATH wave 1 (2013–2014) dataset. Weighted statistics are reported using the balanced repeated replication method and Fay’s correction to account for PATH’s complex study design. Distributions and histograms of the recalled age of initiation of seven different TPs (cigarettes, cigarillos, traditional cigars, filtered cigars, hookah, smokeless tobacco, and e-cigarettes) are reported, as well as the impact of sex and race/ethnicity using Cox proportional hazard models. The impact of cigarette-smoking status on the recalled age of initiation of each tobacco product other than cigarettes was explored. Results: The highest modes of the recalled age of initiation of cigarette use were at 14–15 and 15–16 years old. The distributions of the recalled age of initiation of cigarillos, traditional cigars, filtered cigars, hookah, and smokeless tobacco occurred later, with the highest modes at 15–16 and 17–18 years old. The distribution of the recalled age of initiation of e-cigarettes had a different shape than the other TPs, with the highest mode reported at 27–28 years old. Conclusion: Due to the ever-changing tobacco marketplace, understanding when contemporary adults aged 26–34 years recall initiating TP use is important and will inform prevention researchers.

scholarly journals Impact of bleeding during dual antiplatelet therapy in patients with coronary artery disease

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Ying-Chang Tung ◽  
Lai-Chu See ◽  
Shu-Hao Chang ◽  
Jia-Rou Liu ◽  
Chi-Tai Kuo ◽  
...  
Keyword(s):  
Antiplatelet Therapy ◽  
Dual Antiplatelet Therapy ◽  
East Asian ◽  
Asian Population ◽  
Adverse Outcomes ◽  
Research Database ◽  
Coronary Syndrome ◽  
Asian Patients ◽  
Increased Risk ◽  
The Impact

AbstractThis nationwide retrospective cohort study used the National Health Insurance Research Database of Taiwan to compare the impact of bleeding on clinical outcomes in patients with acute myocardial infarction (AMI) versus chronic coronary syndrome (CCS). Between July 2007 and December 2010, patients with AMI (n = 15,391) and CCS (n = 19,724) who received dual antiplatelet therapy after coronary stenting were identified from the database. AMI was associated with increased risks of MI (AMI vs. CCS: 0.38 vs. 0.16 per 100 patient-months; p < 0.01), all-cause death (0.49 vs. 0.32 per 100 patient-months; p < 0.01), and BARC type 3 bleeding (0.22 vs. 0.13 per 100 patient-months; p < 0.01) at 1 year compared with CCS, while the risk of BARC type 2 bleeding was marginally higher in the CCS patients than in the AMI patients (1.32 vs. 1.4 per 100 person-months; p = 0.06). Bleeding was an independent predictor of MI, stroke, and all-cause death in this East Asian population, regardless of the initial presentation. Among the patients with bleeding, AMI was associated with a higher risk of ischemic events at 1 year after bleeding compared with CCS (MI: 0.34 vs. 0.25 per 100 patient-months; p = 0.06; ischemic stroke: 0.22 vs. 0.13 per 100 patient-months; p = 0.02). The 1-year mortality after bleeding was comparable between the two groups after propensity score weighting. In conclusion, bleeding conferred an increased risk of adverse outcomes in East Asian patients with AMI and CCS.

scholarly journals Comparison of platelet reactivity between prasugrel and ticagrelor in patients with acute coronary syndrome: a meta-analysis

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Mingxiang Wen ◽  
Yaqi Li ◽  
Xiang Qu ◽  
Yanyan Zhu ◽  
Lingfang Tian ◽  
...  
Keyword(s):  
Acute Coronary Syndrome ◽  
Platelet Reactivity ◽  
Weighted Mean Difference ◽  
Meta Analysis ◽  
Reactivity Index ◽  
Cochrane Library ◽  
Coronary Syndrome ◽  
Significant Difference ◽  
Definition Of ◽  
The Cochrane Library

Abstract Background This meta-analysis aimed to compare the effects of prasugrel and ticagrelor on high (HTPR) and low on-treatment platelet reactivity (LTPR) in patients with acute coronary syndrome (ACS). Methods Eligible studies were retrieved from PubMed, Embase, and the Cochrane Library. HTPR and LTPR were evaluated on the basis of the vasodilator-stimulated phosphoprotein platelet reactivity index (VASP-PRI) and P2Y12 reaction units (PRUs). HTPR and LTPR were analyzed using risk ratios (RRs) and their 95% confidence intervals (CIs). Weighted mean difference (WMD) and 95% CI were used to calculate the pooled effect size of platelet reactivity (PR). Results Fourteen eligible studies were obtained, which included 2629 patients treated with ticagrelor (n = 1340) and prasugrel (n = 1289). The pooled results showed that the prasugrel-treated patients had higher platelet reactivity than the ticagrelor-treated patients (PRU: WMD = − 32.26; 95% CI: − 56.48 to − 8.76; P < 0.01; VASP-PRI: WMD = − 9.61; 95% CI: − 14.63 to − 4.60; P = 0.002). No significant difference in HTPR based on PRU was identified between the ticagrelor and prasugrel groups (P = 0.71), whereas a lower HTPR based on VASP-PRI was found in the ticagrelor-treated patients than in the prasugrel-treated patients (RR = 0.30; 95% CI: 0.12–0.75; P = 0.010). In addition, the results showed a lower LTPR was observed in the prasugrel group than in the ticagrelor group (RR = 1.40; 95% CI: 1.08–1.81; P = 0.01). Conclusions Prasugrel might enable higher platelet reactivity than ticagrelor. Ticagrelor could lead to a decrease in HTPR and increase in LTPR. However, this result was only obtained in pooled observational studies. Several uncertainties such as the nondeterminancy of the effectiveness of ticagrelor estimated using VASP-PRI or the definition of HTPR (a high or modifiable risk factor) might have affected our results.

scholarly journals P6419Machine learning in critical care: the role of diabetes and age in acute coronary syndromes

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
E Cenko ◽  
M Van Der Schaar ◽  
J Yoon ◽  
Z Vasiljevic ◽  
S Kedev ◽  
...  
Keyword(s):  
Medical Treatment ◽  
Primary Endpoint ◽  
Left Ventricular ◽  
Adverse Outcomes ◽  
Secondary Endpoint ◽  
Coronary Syndrome ◽  
Increased Risk ◽  
All Cause Mortality ◽  
Patients With Diabetes ◽  
The Impact

Abstract Background Patients with diabetes and non-ST elevation acute coronary syndrome (NSTE-ACS) have an increased risk of mortality and adverse outcomes following percutaneous coronary intervention (PCI). Purpose We aimed to investigate the impact of early, within 24 hours PCI compared with only routine medical treatment on clinical outcomes in a large international cohort of patients with NSTE-ACS and diabetes. Methods We identified 1,250 patients with diabetes and NSTE-ACS from a registry-based population between October 2010 and April 2016. The primary endpoint was 30-day all-cause mortality. The secondary endpoint was the composite outcome of 30-day all-cause mortality and left ventricular dysfunction (ejection fraction <40%). We undertook analyses to explore the heterogeneity of treatment effects using meta-classification (MC) algorithms followed by propensity score matching and inverse-probability-of-treatment weighting (IPTW) from a landmark of 24 hours from hospitalization. Results Of 1,250 NSTE-ACS first-day survivors with diabetes (median age 67 years; 59%, men), 470 (37.6%) received early PCI and 780 routine medical treatment. The overall 30-day all-cause mortality rates were higher in the routine medical treatment than the early PCI group (6.3% vs. 2.5%). The prediction results of the MC algorithms accounted for only one interaction term that was statistically significant: age ≥65 years. After propensity-matched analysis as well as IPTW, early PCI was associated with reduced 30-day all-cause mortality in the older age (OR: 0.35; 95% CI: 0.14 to 0.92 and 0.43; 95% CI: 0.21 to 0.86, respectively), whereas younger age had no association with the primary endpoint. Similar results were also obtained for the secondary endpoint. Conclusions Among patients with diabetes hospitalized for NSTE-ACS, an early, within 24 hours, PCI strategy is associated with reduced odds of 30-day mortality only for patients aged 65 years or over. MC algorithms provide accurate identification of treatment effect modifiers.

scholarly journals The Impact of Cigarette Smoking on Prognosis in Small Adenocarcinomas of the Lung: The Association Between Histologic Subtype and Smoking Status

2008 ◽  
Vol 3 (9) ◽  
pp. 958-962 ◽  
Author(s):  
Yukinori Sakao ◽  
Hideaki Miyamoto ◽  
Shiaki Oh ◽  
Nobumasa Takahashi ◽  
Tomoya Inagaki ◽  
...  
Keyword(s):  
Cigarette Smoking ◽  
Smoking Status ◽  
Histologic Subtype ◽  
The Impact

scholarly journals Psychological coping and recurrent major adverse cardiac events following acute coronary syndrome

2015 ◽  
Vol 207 (3) ◽  
pp. 256-261 ◽  
Author(s):  
Nadine Messerli-Bürgy ◽  
Gerard J. Molloy ◽  
Lydia Poole ◽  
Anna Wikman ◽  
Juan Carlos Kaski ◽  
...  
Keyword(s):  
Acute Coronary Syndrome ◽  
Adverse Outcomes ◽  
Event Free Survival ◽  
Cardiac Events ◽  
Free Survival ◽  
Coronary Syndrome ◽  
Adverse Cardiac Events ◽  
Task Oriented ◽  
The Impact ◽  
Psychological Coping

BackgroundDepressed mood and stress are associated with recurrent adverse outcomes following acute coronary syndrome (ACS), but the impact of psychological coping style has not been evaluated in detail.AimsWe tested the relationship between task-oriented coping and event-free survival following ACS.MethodWe followed 158 patients with ACS for an average of 59.8 months for major adverse cardiac outcomes. Psychological coping was assessed with the Coping Inventory of Stressful Situations.ResultsCompared with patients in the lower half of the distribution, those reporting higher task-oriented coping had a reduced hazard of adverse cardiac events (hazard ratio (HR) = 0.28, 95% CI 0.11–0.68, P=0.005) independently of demographic, clinical and behavioural covariates. The combination of low task-oriented coping and high depressive symptoms showed a strong association with adverse outcomes (HR = 6.25, 95% CI 1.88–20.82, P=0.003).ConclusionsThe tendency to cope using task-oriented strategies may promote event-free survival following ACS.

Sign in / Sign up

Export Citation Format

Share Document