Adverse events in cardiovascular disease patients taking clopidogrel: impact of CYP2C19 genotype polymorphisms

2020 ◽  
Author(s):  
Zegan Liu ◽  
Qian Hu ◽  
Li Tang ◽  
Junlong Ma ◽  
Jiangfan Cai ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Cardiovascular Diseases ◽  
Adverse Events ◽  
Antiplatelet Therapy ◽  
Onset Time ◽  
Cyp2c19 Genotype ◽  
Significant Difference ◽  
Main Factors ◽  
The Impact ◽  
Cyp2c19 Polymorphisms

Abstract Background: Clopidogrel combined with aspirin in antiplatelet therapy is the first-line clinical regimen for cardiovascular diseases. The CYP2C19 gene influences the absorption and metabolism of clopidogrel and its polymorphisms affect antiplatelet therapy drug efficacy, which may lead to adverse events including stent thrombosis and haemorrhage. The main objective of this study was to explore the impact of CYP2C19 polymorphisms on adverse events in cardiovascular disease patients.Methods:We recruited 350 patients taking clopidogrel and performed CYP2C19 genotype testing. Adverse event information was collected through telephone follow-up. According to CYP2C19 genotype results, patients were divided into three groups: poor metabolism (PM) group, extensive metabolism (EM) group and intermediate metabolism (IM) group. The number of adverse events was compared between the three groups using the chi-squared test and the onset time of adverse events was analysed using the log-rank test. The main factors affecting adverse events were analysed using binary logistic analysis.Results: In total, 326 patients were included in the analysis: 143 patients were in the EM group, 129 patients were in the IM group and 54 patients were in the PM group. In this cohort, 127 adverse events were noted, which occurred in 88 patients. There was no significant difference in the occurrence of adverse events between the EM group and PM group (P=0.185). The median survival times of adverse events in the EM, IM and PM groups were 112 days, 137.5 days and 169 days, respectively, with no significant differences between the three groups (P=0.8713).Conclusion:We found that CYP2C19 polymorphisms were not necessarily associated with adverse events in patients with cardiovascular diseases taking clopidogrel. Rather, the main factors influencing the occurrence of adverse events were concomitant diseases such as hypertension, diabetes and hyperlipidaemia.

scholarly journals Impact of cytochrome P450 2C19 polymorphisms on the clinical efficacy and safety of voriconazole: an update systematic review and meta-analysis

2021 ◽  
Author(s):  
Ying Zhang ◽  
Xu Hao ◽  
Kelu Hou ◽  
Lei Hu ◽  
Jingyuan Shang ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Adverse Events ◽  
Success Rate ◽  
Clinical Efficacy ◽  
Search Algorithm ◽  
Efficacy And Safety ◽  
Increased Risk ◽  
Significant Difference ◽  
The Impact ◽  
Cyp2c19 Polymorphisms

Aims: To assess the impact of cytochrome P450 (CYP) 2C19 polymorphisms on the clinical efficacy and safety of voriconazole. Methods: We systematically searched PubMed, EMBASE, CENTRAL, ClinicalTrials.gov, and three Chinese databases from their inception to March 18, 2021 using a predefined search algorithm to identify relevant studies. Studies that reported voriconazole-treated patients and information on CYP2C19 polymorphisms were included. The efficacy outcome was success rate. The safety outcomes included overall adverse events, hepatotoxicity and neurotoxicity. Results: A total of 20 studies were included. Intermediate metabolizers (IMs) and Poor metabolizers (PMs) were associated with increased success rates compared with normal metabolizers (NMs) (risk ratio (RR): 1.18, 95% confidence interval (CI): 1.03~1.34, I2=0%, p=0.02; RR: 1.28, 95%CI: 1.06~1.54, I2=0%, p=0.01). PMs were at increased risk of overall adverse events in comparison with NMs and IMs (RR: 2.18, 95%CI: 1.35~3.53, I2=0%, p=0.001; RR: 1.80, 95% CI: 1.23~2.64, I2=0%, p=0.003). PMs demonstrated a trend towards an increased incidence of hepatotoxicity when compared with NMs (RR: 1.60, 95%CI: 0.94~2.74, I2=27%, p=0.08), although there was no statistically significant difference. In addition, there was no significant association between CYP2C19 polymorphisms and neurotoxicity. Conclusions: IMs and PMs were at a significant higher success rate in comparison with NMs. PMs were significantly associated with an increased incidence of all adverse events compared with NMs and IMs. Researches are expected to further confirm these findings. Additionally, the relationship between hepatotoxicity and CYP2C19 polymorphisms deservers clinical attention.

scholarly journals Impact of concomitant medication use and immune-related adverse events on response to immune checkpoint inhibitors

Immunotherapy ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 141-149 ◽  
Author(s):  
Shipra Gandhi ◽  
Manu Pandey ◽  
Nischala Ammannagari ◽  
Chong Wang ◽  
Mark J Bucsek ◽  
...  
Keyword(s):  
Adverse Events ◽  
Clinical Benefit ◽  
Immune Checkpoint Inhibitors ◽  
Concomitant Medication ◽  
Checkpoint Inhibitors ◽  
Metastatic Cancer ◽  
Medication Use ◽  
Significant Difference ◽  
Β Blockers ◽  
The Impact

Aim: Patients receiving checkpoint inhibitors (CPI) are frequently on other medications for co-morbidities. We explored the impact of concomitant medication use on outcomes. Materials & methods: 210 metastatic cancer patients on CPI were identified and association between concomitant medication use and immune-related adverse events with clinical outcomes was determined. Results: Aspirin, metformin, β-blockers and statins were not shown to have any statistically significant difference on clinical benefit. 26.3% patients with clinical benefit developed rash versus 11.8% without clinical benefit (p < 0.05) on multivariate analysis. Conclusion: Use of common prescription and nonprescription medications in patients with multiple co-morbidities appears safe and does not have an adverse effect on CPI efficacy. The presence of rash predicted for a better response.

scholarly journals Sediment properties and CO<sub>2</sub> efflux from intact and cleared temperate mangrove forests

2015 ◽  
Vol 12 (20) ◽  
pp. 6169-6180 ◽  
Author(s):  
R. H. Bulmer ◽  
C. J. Lundquist ◽  
L. Schwendenmann
Keyword(s):  
New Zealand ◽  
Mangrove Forest ◽  
Abiotic Factors ◽  
Co2 Uptake ◽  
Co2 Efflux ◽  
Mangrove Forests ◽  
Sediment Grain Size ◽  
Significant Difference ◽  
Main Factors ◽  
The Impact

Abstract. Temperate mangrove forests in New Zealand have increased in area over recent decades. Expansion of temperate mangroves in New Zealand is associated with perceived loss of other estuarine habitats, and decreased recreational and amenity values, resulting in clearing of mangrove forests. In the tropics, changes in sediment characteristics and carbon efflux have been reported following mangrove clearance. This is the first study in temperate mangrove (Avicennia marina) forests investigating the impact of clearing on sediment CO2 efflux and associated biotic and abiotic factors. Sediment CO2 efflux rates from intact (168.5 ± 45.8 mmol m−2 d−1) and cleared (133.9 ± 37.2 mmol m−2 d−1) mangrove forests in New Zealand are comparable to rates measured in tropical mangrove forests. We did not find a significant difference in sediment CO2 efflux rates between intact and cleared temperate mangrove forests. Pre-shading the sediment for more than 30 min prior to dark chamber measurements was found to have no significant effect on sediment CO2 efflux. This suggests that the continuation of photosynthetic CO2 uptake by biofilm communities was not occurring after placement of dark chambers. Rather, above-ground mangrove biomass, sediment temperature and chlorophyll a concentration were the main factors explaining the variability in sediment CO2 efflux in intact mangrove forests. The main factors influencing sediment CO2 efflux in cleared mangrove forest sites were sediment organic carbon concentration, nitrogen concentration and sediment grain size. Our results show that greater consideration should be given regarding the rate of carbon released from mangrove forest following clearance and the relative contribution to global carbon emissions.

Impact of obesity in patients with metastatic urothelial carcinoma.

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 346-346
Author(s):  
Amanda Leiter ◽  
John Doucette ◽  
Susanne Krege ◽  
Chia-Chi Lin ◽  
Noah M. Hahn ◽  
...  
Keyword(s):  
Adverse Events ◽  
Urothelial Cancer ◽  
Normal Weight ◽  
Phase Iii ◽  
Survival Outcomes ◽  
Similar Response ◽  
Obese Patients ◽  
Metastatic Urothelial Cancer ◽  
Significant Difference ◽  
The Impact

346 Background: Obesity has been associated with worse outcomes in patients with clinically localized urothelial cancer. However, the impact of obesity on outcomes of patients with metastatic disease has not previously been evaluated. Methods: Data from 537 patients were aggregated from eight phase II and phase III clinical trials investigating first-line cisplatin-based combination therapy in metastatic urothelial cancer. Chemotherapy regimen, adverse events, treatment response, and survival outcomes were compared across body mass index (BMI) and body surface area (BSA) categories. Results: BMI was classified according to WHO criteria (<18.5 underweight (4.1 % of patients), 18.5-24.99 normal weight (42.8%), 25-29.99 overweight (41.0%), >30 obese (12.1%)). BSA was classified as either below (56.8% of patients) or greater than or equal to (43.2%) the European average (1.91 m2 for males and 1.71 m2 for females). There was no significant difference in number of chemotherapy cycles across BMI and BSA categories. Patients’ treatment regimens significantly differed across BMI (p=0.02) and BSA (p<0.01) categories, with patients with higher BMI category and average or above BSA more likely to receive gemcitabine-cisplatin-based therapy rather than MVAC (methotrexate, vinblastine, doxorubicin, and cisplatin)-based or other therapy regimens. There was no significant difference in adverse events across BMI categories, but the incidence of embolic events was significantly higher in patients with an average or higher BSA (6.6%) than those with a lower than average BSA (2.7%) (p=0.03). There was no significant difference in response rate or survival outcomes (overall and progression-free) amongst BMI and BSA categories. Conclusions: Obese patients with metastatic urothelial cancer on cisplatin-based therapies have similar response rates and survival outcomes to non-obese patients. Toleration of cisplatin-based therapy is similar across BMI and BSA categories, with the exception of a higher incidence of embolic events in patients with an above average BSA.

The impact of steroid use on efficacy of immunotherapy among patients with lung cancer who have developed immune-related adverse events.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e20583-e20583
Author(s):  
Kazushige Wakuda ◽  
Taichi Miyawaki ◽  
Eriko Miyawaki ◽  
Nobuaki Mamesaya ◽  
Takahisa Kawamura ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Adverse Events ◽  
Checkpoint Inhibitors ◽  
Smoking Status ◽  
Performance Status ◽  
Objective Response ◽  
Systemic Steroid ◽  
Steroid Group ◽  
Significant Difference ◽  
The Impact

e20583 Background: Systemic steroids use before starting immune checkpoint inhibitors (ICI) has negative impacts on survival. The aim of this study was to evaluate whether steroid against immune-related adverse events (irAE) reduces efficacy in patients with non-small cell lung cancer (NSCLC). Methods: We retrospectively reviewed patients who had advanced NSCLC and undergone ICI therapy between December 2015 and June 2018. Patients whose irAE was treated with ≥ 10mg/day of predonisone were classified into steroid group (S), otherwise into non-steroid group (N). Results: A total of 257 patients (pts) were treated with ICI and irAEs was observed in 103 pts (40%). Twenty-eight pts were S-group and 75 patients were N-group. There was no significant difference in age, sex, stage, performance status, histology, smoking status, gene alteration, expression of PD-L1, or treatment line between the groups. Main irAEs included pneumonitis (43% in S-group / 12% in N-group), diarrhea or colitis (25% / 9%), rash (21% / 20%), and hypothyroidism (14% / 37%). Grade 2 or higher irAEs were pneumonitis in 39% / 0%, diarrhea or colitis in 21% / 5%, hypothyroidism in 7% / 19%. Among S-group, steroids were used for pneumonitis in 11 pts, diarrhea or colitis in 7 pts, stomatitis in 2 pts, and rash in 2 pts. There was no significant difference in overall survival (median; 14.5 vs 30.0 months, P = 0.30, Hazard ratio, 0.69), progression-free survival (median; 7.8 vs 9.6 months, p = 0.11, Hazard ration, 0.65), and objective response rate (46% vs 41%, p = 0.64), respectively. Conclusions: Systemic steroid was mainly used in pts with ≥Gr2 pneumonitis or colitis. This study indicated that steroids use did not reduce efficacy of ICI. Thus, steroid should not be avoided in patients with moderate to severe irAEs with concern over reducing efficacy.

P6355The behavior of atrial fibrillation in patients with heart failure hospitalization

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
M Fukunaga ◽  
K Hirose ◽  
A Isotani ◽  
T Morinaga ◽  
K Ando
Keyword(s):  
Heart Failure ◽  
Atrial Fibrillation ◽  
Cardiovascular Disease ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Significant Difference ◽  
The Impact

Abstract Background Relationship between atrial fibrillation (AF) and heart failure (HF) is often compared with proverbial question of which came first, the chicken or the egg. Some patients showing AF at the HF admission result in restoration of sinus rhythm (SR) at discharge. It is not well elucidated that the restoration into SR during hospitalization can render the preventive effect for rehospitalization. Purpose To investigate the impact of restoration into SR during hospitalization for readmission rate of the HF patients showing AF. Methods We enrolled consecutive 640 HF patients hospitalized from January 2015 to December 2015. Patients data were retrospectively investigated from medical record. Patients showing atrial fibrillation on admission but unrecognized ever were defined as “incident AF”; patients with AF diagnosed before admission were defined as “prevalent AF”. Primary endpoint was a composite of death from cardiovascular disease or hospitalization for worsening heart failure. Secondary endpoints were death from cardiovascular disease, unplanned hospitalization related to heart failure, and any hospitalization. Results During mean follow up of 19 months, 139 patients (22%) were categorized as incident AF and 145 patients (23%) were categorized as prevalent AF. Among 239 patients showing AF on admission, 44 patients were discharged in SR (39 patients in incident AF and 5 patients in prevalent AF). Among incident AF patients, the primary composite end point occurred in significantly fewer in those who discharged in SR (19% vs. 42% at 1-year; 23% vs. 53% at 2-year follow-up, p=0.005). To compare the risk factors related to readmission due to HF with the cox proportional-hazards model, AF only during hospitalization [Hazard Ratio (HR)=0.37, p<0.01] and prevalent AF (HR=1.67, p=0.04) was significantly associated. There was no significant difference depending on LVEF. Conclusion Newly diagnosed AF with restoration to SR during hospitalization was a good marker to forecast future prognosis.

scholarly journals Air pollutants and outpatient visits for cardiovascular disease in a severe haze-fog city: Shijiazhuang, China

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Fengzhu Tan ◽  
Weijie Wang ◽  
Sufen Qi ◽  
Haidong Kan ◽  
Xinpei Yu ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Air Pollutants ◽  
Attributable Risk ◽  
Air Pollutant ◽  
Outpatient Visits ◽  
Pollutant Concentrations ◽  
Main Factors ◽  
High Concentrations ◽  
Air Pollutant Concentrations ◽  
The Impact

Abstract Background Many studies have reported the impact of air pollution on cardiovascular disease (CVD), but few of these studies were conducted in severe haze-fog areas. The present study focuses on the impact of different air pollutant concentrations on daily CVD outpatient visits in a severe haze-fog city. Methods Data regarding daily air pollutants and outpatient visits for CVD in 2013 were collected, and the association between six pollutants and CVD outpatient visits was explored using the least squares mean (LSmeans) and logistic regression. Adjustments were made for days of the week, months, air temperature and relative humidity. Results The daily CVD outpatient visits for particulate matter (PM10 and PM2.5), sulphur dioxide (SO2), nitrogen dioxide (NO2), carbon monoxide (CO), and ozone (O3) in the 90th-quantile group were increased by 30.01, 29.42, 17.68, 14.98, 29.34%, and − 19.87%, respectively, compared to those in the <10th-quantile group. Odds ratios (ORs) and 95% confidence intervals (CIs) for the increase in daily CVD outpatient visits in PM10 300- and 500-μg/m3, PM2.5 100- and 300-μg/m3 and CO 3-mg/m3 groups were 2.538 (1.070–6.020), 7.781 (1.681–36.024), 3.298 (1.559–6.976), 8.72 (1.523–49.934), and 5.808 (1.016–33.217), respectively, and their corresponding attributable risk percentages (AR%) were 60.6, 87.15, 69.68, 88.53 and 82.78%, respectively. The strongest associations for PM10, PM2.5 and CO were found only in lag 0 and lag 1. The ORs for the increase in CVD outpatient visits per increase in different units of the six pollutants were also analysed. Conclusions All five air pollutants except O3 were positively associated with the increase in daily CVD outpatient visits in lag 0. The high concentrations of PM10, PM2.5 and CO heightened not only the percentage but also the risk of increased daily CVD outpatient visits. PM10, PM2.5 and CO may be the main factors of CVD outpatient visits.

Abstract 16144: The Impact of Ventricular Pacing for Elderly Patients With Pacemaker Implantation: Over One Decade and Large Cohort Analysis

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Ayako Kamijima ◽  
Kohei Ishibashi ◽  
Mitsuru Wada ◽  
Ikutaro Nakajima ◽  
Koji Miyamoto ◽  
...  
Keyword(s):  
Adverse Events ◽  
Elderly Patients ◽  
Cohort Analysis ◽  
Pacemaker Implantation ◽  
The Elderly ◽  
Ventricular Pacing ◽  
Kaplan Meier ◽  
Long Term Effect ◽  
Significant Difference ◽  
The Impact

Introduction: Previous studies showed that ventricular pacing (VP) increased the cardiac event of patients with pacemaker (PM). However, these studies consisted of patients under 75 years old and the influence of VP for elderly patients (over 75 years old) is still unclear. We sought to evaluate long-term effect of VP for elderly patients. Methods: A total of 782 patients (mean 57.2 years old) underwent PM implantation for brady-arrhythmia were enrolled from 1978 to 2005. The elderly patients (199 patients, over 75 years old, mean 80.7 years old) and all patients were divided into VP and non-VP group, and evaluated adverse events (death or readmission for heart failure). Results: The mean follow-up period was 10.1 years and 84 elderly patients (42%) developed adverse events. Kaplan-Meier analysis revealed that (1) VP increased the adverse event in all patients. (2) There was no significant difference in the adverse events of elderly patients between VP and non-VP group (Fig). Conclusion: VP may be tolerated for elderly patients with PM, whereas VP has no effect for the prognosis.

scholarly journals Impact of Anemia on the Outcomes of Endoscopic Intervention in High-Risk NUGIB Patients

2020 ◽  
Author(s):  
Jixue Tan ◽  
Tian Lan ◽  
Shuai Bai ◽  
ling liu
Keyword(s):  
High Risk ◽  
Adverse Events ◽  
Hemoglobin Level ◽  
Bleeding Rate ◽  
Endoscopic Intervention ◽  
Icu Stay ◽  
Significant Difference ◽  
Severe Group ◽  
The Impact ◽  
Length Of Icu Stay

Abstract Background: It is common for high-risk, non-variceal upper gastrointestinal bleeding (NUGIB) patients coexisting anemia, but the role of anemia on the prognosis of endoscopic intervention is not clear. The aim of this study was to assess the impact of hemoglobin level on outcomes of endoscopic intervention in high-risk NUGIB patients. Methods: A retrospective study was performed on high-risk (Glasgow-Blatchford score ≥7) NUGIB patients who underwent endoscopic intervention within 24h of presentation. Patients were divided into three groups based on hemoglobin level before intervention: severe (<7g/dl), moderate (7g/dl ≤hemoglobin <9g/dl) and mild (≥9g/dl) group. Outcomes included mortality, length of ICU stay, re-bleeding rate, procedural adverse events, length of hospital stay, adverse events and transfusion requirement. Results: A total of 156 patients received endoscopic intervention were identified, 88 in the severe group, 45 in the moderate group, and 23 in the mild group. The total mortality rate in 45 days was 2%, and the re-bleeding rate was 21%. There was no significant difference in mortality, re-bleeding rate or length of ICU stay among the three groups. The average days of hospitalization in the severe group was significantly longer than that of the moderate group (13 vs 8, P < 0.05). No adverse events occurred. Low hemoglobin level was a predictor for more red-cell transfusion (OR=5.94, 2.69-13.11) and plasma transfusion (OR=2.34,1.21-4.51). Conclusions: Anemia does not affect the mortality and rebleeding of endoscopic intervention in high-risk NUGIB patients, but is associated with more transfusion and longer hospitalization.

scholarly journals Predictive value of clinical toxicities of chemotherapy with fluoropyrimidines and oxaliplatin in colorectal cancer by DPYD and GSTP1 gene polymorphisms

2020 ◽  
Author(s):  
Xunwei Deng ◽  
Jingyuan Hou ◽  
Qiaoting Deng ◽  
Zhixiong Zhong
Keyword(s):  
Colorectal Cancer ◽  
Adverse Events ◽  
Direct Sequencing ◽  
Dihydropyrimidine Dehydrogenase ◽  
Severe Toxicity ◽  
Nucleotide Polymorphisms ◽  
Mutant Type ◽  
Severe Vomiting ◽  
Significant Difference ◽  
The Impact

Abstract Background: Fluoropyrimidines and platinum are still widely used for colorectal cancer (CRC) management. Several studies have reported that mutations of dihydropyrimidine dehydrogenase (DPYD) and glutathione S-transferase pi-1 (GSTP1) polymorphisms are related to Chemotherapy-related adverse events. In the present study, we purposed to assess the impact of DPYD and GSTP1 variants on the toxicity of adjuvant chemotherapy risk among the Hakka population, minimize adverse events, and to maximize therapy outcome for individualized treatment.Methods: Genotyping was examined in 104 patients diagnosed with CRC cases and receiving fluoropyrimidine and platinum drugs based chemotherapy regimen by direct sequencing of DPYD and GSTP1 polymorphisms. Three DPYD variants including *2A, *5A, *9A, and GSTP1 c.313A>G were analyzed and clinical outcomes were assessed.Results: The data suggest that the incidence of DPYD*5A, DPYD*9A, and GSTP1 c.313A>G variants were 38.4%, 24%, and 32.7%, respectively. DPYD*2A variant was not found. A total of 23 patients (22.1%) suffered severe vomiting and 19 patients (18.3%) suffered severe anemia. DPYD*5A polymorphism was found significantly associated with grade 3/4 ulceration (p = 0.001). GSTP1 was determined to be an independent risk factor for severe vomiting and skin ulceration (p = 0.042 and p = 0.018, respectively). Patients with GSTP1 c. 313A>G mutant type contributed to a higher risk for grade severe toxicity compared with wild genotype (p = 0.027). Nevertheless, no significant difference was found between patients with DPYD*2A, *5A, *9A for chemotherapeutic toxicity.Conclusions: The results demonstrated that GSTP1 polymorphisms were useful predictors of severe events. Screening of single nucleotide polymorphisms of GSTP1 in colorectal cancer patients before chemotherapy may help to realize personalized therapy.

Sign in / Sign up

Export Citation Format

Share Document