Effect of genotype-guided strategy in East Asian vs. Caucasian patients after percutaneous coronary intervention: insight from the TAILOR-PCI trial.
Ontology highlight
ABSTRACT:
SUBMITTER: Kim HK
PROVIDER: S-EPMC7797838 | biostudies-literature | 2020 Dec
REPOSITORIES: biostudies-literature
Publications
Effect of genotype-guided strategy in East Asian <i>vs.</i> Caucasian patients after percutaneous coronary intervention: insight from the TAILOR-PCI trial.
Kim Hyun Kuk HK Sibbing Dirk D Jeong Young-Hoon YH
Journal of thoracic disease 20201201 12
Similar Datasets
Project description:ImportanceAfter percutaneous coronary intervention (PCI), patients with CYP2C19*2 or *3 loss-of-function (LOF) variants treated with clopidogrel have increased risk of ischemic events. Whether genotype-guided selection of oral P2Y12 inhibitor therapy improves ischemic outcomes is unknown.ObjectiveTo determine the effect of a genotype-guided oral P2Y12 inhibitor strategy on ischemic outcomes in CYP2C19 LOF carriers after PCI.Design, setting, and participantsOpen-label randomized clinical trial of 5302 patients undergoing PCI for acute coronary syndromes (ACS) or stable coronary artery disease (CAD). Patients were enrolled at 40 centers in the US, Canada, South Korea, and Mexico from May 2013 through October 2018; final date of follow-up was October 2019.InterventionsPatients randomized to the genotype-guided group (n = 2652) underwent point-of-care genotyping. CYP2C19 LOF carriers were prescribed ticagrelor and noncarriers clopidogrel. Patients randomized to the conventional group (n = 2650) were prescribed clopidogrel and underwent genotyping after 12 months.Main outcomes and measuresThe primary end point was a composite of cardiovascular death, myocardial infarction, stroke, stent thrombosis, and severe recurrent ischemia at 12 months. A secondary end point was major or minor bleeding at 12 months. The primary analysis was in patients with CYP2C19 LOF variants, and secondary analysis included all randomized patients. The trial had 85% power to detect a minimum hazard ratio of 0.50.ResultsAmong 5302 patients randomized (median age, 62 years; 25% women), 82% had ACS and 18% had stable CAD; 94% completed the trial. Of 1849 with CYP2C19 LOF variants, 764 of 903 (85%) assigned to genotype-guided therapy received ticagrelor, and 932 of 946 (99%) assigned to conventional therapy received clopidogrel. The primary end point occurred in 35 of 903 CYP2C19 LOF carriers (4.0%) in the genotype-guided therapy group and 54 of 946 (5.9%) in the conventional therapy group at 12 months (hazard ratio [HR], 0.66 [95% CI, 0.43-1.02]; P = .06). None of the 11 prespecified secondary end points showed significant differences, including major or minor bleeding in CYP2C19 LOF carriers in the genotype-guided group (1.9%) vs the conventional therapy group (1.6%) at 12 months (HR, 1.22 [95% CI, 0.60-2.51]; P = .58). Among all randomized patients, the primary end point occurred in 113 of 2641 (4.4%) in the genotype-guided group and 135 of 2635 (5.3%) in the conventional group (HR, 0.84 [95% CI, 0.65-1.07]; P = .16).Conclusions and relevanceAmong CYP2C19 LOF carriers with ACS and stable CAD undergoing PCI, genotype-guided selection of an oral P2Y12 inhibitor, compared with conventional clopidogrel therapy without point-of-care genotyping, resulted in no statistically significant difference in a composite end point of cardiovascular death, myocardial infarction, stroke, stent thrombosis, and severe recurrent ischemia based on the prespecified analysis plan and the treatment effect that the study was powered to detect at 12 months.Trial registrationClinicalTrials.gov Identifier: NCT01742117.
| S-EPMC7448831 | biostudies-literature
Project description:The purpose of the present study is to determine the effect of Percutaneous Collagen Induction (PCI) on the epidermis and dermis, including the systemic inflammatory response on gene expression level using microarray analysis. PCI Therapy is an alternative for safely treating wrinkles and scars and smoothening the skin. Therefore animal experiments were performed using 31 male Sprague-Dawley rats (350–375 g), age 4 month, randomly assigned into three groups: group (A) (n=24: needling plus skin care), group (B) (n=6: skincare only, controls after 24 h) and group (C) (n=1: negative control). Rats were anesthetized, shaved, and received a 30% total body surface area (TBSA) scald needling (10min) to induce percutaneous collagen, using a medical needling instrument (Environ® Medical Roll-CITTM, Vivida SA cc, Cape Town, South Africa). After needling surgery, the rats were immediately prepared with high levels of vitamin A cream and vitamin C cream, applied topically after cleaning once per day. The control group (C) rats received no injury, no skin care, no treatment, no anesthesia, and no analgesia. Gene expression analyses were performed 1 h, 24 h, 2, 4, and 8 weeks after PCI surgery. To confirm RNA expression in rat skin, self developed microarrays including genes like cytokines, such as vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF 2), keratinocyte growth factor (KGF), epidermal growth factor (EGF), and transforming growth factors (TGF ß1, ß2, ß3) were used.
2008-05-31 | GSE11617 | GEO
Project description:Background TAILOR-PCI (Tailored Antiplatelet Initiation to Lessen Outcomes due to decreased Clopidogrel Response After Percutaneous Coronary Intervention) studied genotype-guided selection of antiplatelet therapy after percutaneous coronary intervention versus conventional therapy with clopidogrel. The presence of CYP2C19 loss-of-function alleles in patients treated with clopidogrel may be associated with increased risk for ischemic events. We report a prespecified sex-specific analysis of genotyping and associated cardiovascular outcomes from this study. Methods and Results Associations between sex and major adverse cardiac events (MACE: cardiovascular death, myocardial infarction, stroke, stent thrombosis, and severe recurrent ischemia) and Bleeding Academic Research Consortium (BARC) bleeding at 12 months were analyzed using Cox proportional-hazards models. Among 5276 randomized patients, loss-of-function carriers were observed in ≈36% of both sexes, and >80% of carriers were heterozygotes. At 12 months, after adjustment for baseline differences, risks of MACE (HR , 1.28 [0.97 to 1.68]; P=0.088) and BARC bleeding (hazard ratio [HR], 1.36 [0.91 to 2.05]; P=0.14) were comparable among women and men. There were no significant interactions between sex and treatment strategy for MACE interaction P value (Pint=0.59) or BARC bleeding (Pint=0.47) nor for sex and genotype (MACE Pint=0.15, and BARC bleeding Pint=0.60). Conclusions CYP2C19 loss-of-function alleles were present in ≈1 in 3 women and men. Women had similar adjusted risks of MACE and bleeding as men following percutaneous coronary intervention. Genotype-guided therapy did not significantly reduce the risk of MACE or bleeding relative to conventional therapy for both sexes. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01742117.
| S-EPMC9238632 | biostudies-literature
Project description:PurposeChronic kidney disease (CKD) is a risk factor for ischemic and bleeding events with dual antiplatelet therapy after percutaneous coronary intervention (PCI). Whether the presence of CYP2C19 loss of function (LOF) alleles modifies this risk, and whether a genotype-guided (GG) escalation of P2Y12 inhibitor therapy post PCI is safe in this population is unclear.MethodsThis was a post hoc analysis of randomized patients in TAILOR PCI. Patients were divided into two groups based on estimated glomerular filtration rate (eGFR) threshold of < 60 ml/min/1.73 m2 for CKD (n = 539) and non-CKD (n = 4276). The aggregate of cardiovascular death, stroke, myocardial infarction, stent thrombosis, and severe recurrent coronary ischemia at 12-months post-PCI was assessed as the primary endpoint. Secondary endpoint was major or minor bleeding.ResultsMean (standard deviation) eGFR among patients with CKD was 49.5 (8.4) ml/min/1.72 m2. Among all patients, there was no significant interaction between randomized strategy and CKD status for any endpoint. Among LOF carriers, the interaction between randomized strategy and CKD status on composite ischemic outcome was not significant (p = 0.2). GG strategy was not associated with an increased risk of bleeding in either CKD group.ConclusionsIn this exploratory analysis, escalation of P2Y12 inhibitor therapy following a GG strategy did not reduce the primary outcome in CKD. However, P2Y12 inhibitor escalation following a GG strategy was not associated with increased bleeding risk in CKD. Larger studies in CKD are needed.Clinical trial registrationhttps://clinicaltrials.gov/ct2/show/NCT01742117?term=TAILOR-PCI&draw=2&rank=1 . NCT01742117.
| S-EPMC10225474 | biostudies-literature
Project description:AimThe aim of this study was to evaluate the feasibility of heparinised saline as flushing media for frequency-domain optical coherence tomography (FD-OCT) image acquisition during percutaneous coronary intervention (PCI) optimisation.Methods and resultsTwenty-seven patients undergoing FD-OCT-guided PCI were enrolled. Heparinised saline was injected into the coronary during FD-OCT image acquisition. A total of 118 runs were analysed for image quality and diagnostic value. FD-OCT runs were categorised as follows: good runs (GRs), clinically usable runs (CURs) and clinically not usable runs (NURs); GRs and CURs were combined as clinically effective runs (ERs). Saline FD-OCT enabled visualisation of all possible coronary lesions. Of the 118 runs analysed, 61%, 27.1%, 11.9% and 88.1% were GRs, CURs, NURs and ERs, respectively. Sixty-one percent of total runs were left coronary system (LCS) and 39% were right coronary system (RCS) runs. Among LCS runs, 55.6%, 30.6%, 13.8% and 86.2% were GRs, CURs, NURs and ERs, respectively. Among RCS runs, 69.6%, 21.7%, 8.7% and 91.3% were GRs, CURs, NURs and ERs, respectively.ConclusionThis is the first study to demonstrate the technical feasibility of isolated saline FD-OCT for PCI optimisation.
| S-EPMC7474129 | biostudies-literature
Project description:ObjectiveTo examine the relationship between body mass index (BMI) and outcomes after percutaneous coronary intervention (PCI) in a multiethnic South East Asian population.SettingFifteen participating cardiology centres contributed to the Malaysian National Cardiovascular Disease Database-Percutaneous Coronary Intervention (NCVD-PCI) registry.Participants28 742 patients from the NCVD-PCI registry who had their first PCI between January 2007 and December 2014 were included. Those without their BMI recorded or BMI <11 kg/m2 or >70 kg/m2 were excluded.Main outcome measuresIn-hospital death, major adverse cardiovascular events (MACEs), vascular complications between different BMI groups were examined. Multivariable-adjusted HRs for 1-year mortality after PCI among the BMI groups were also calculated.ResultsThe patients were divided into four groups; underweight (BMI <18.5 kg/m2), normal BMI (BMI 18.5 to <23 kg/m2), overweight (BMI 23 to <27.5 kg/m2) and obese (BMI ≥27.5 kg/m2). Comparison of their baseline characteristics showed that the obese group was younger, had lower prevalence of smoking but higher prevalence of diabetes, hypertension and dyslipidemia. There was no difference found in terms of in-hospital death, MACE and vascular complications after PCI. Multivariable Cox proportional hazard regression analysis showed that compared with normal BMI group the underweight group had a non-significant difference (HR 1.02, p=0.952), while the overweight group had significantly lower risk of 1-year mortality (HR 0.71, p=0.005). The obese group also showed lower HR but this was non-significant (HR 0.78, p=0.056).ConclusionsUsing Asian-specific BMI cut-off points, the overweight group in our study population was independently associated with lower risk of 1-year mortality after PCI compared with the normal BMI group.
| S-EPMC5695449 | biostudies-literature
Project description:BackgroundDifferences in carcinogenesis and therapeutic efficacy according to ethnicity have been reported for lung cancer, and understanding differences in genetic mutation profiles among ethnicities is important for interpreting the results of clinical trials, preventing carcinogenesis, and individualizing treatment. However, no studies have focused on differences in mutation profiles among different ethnicities using large-scale genomic analysis data with detailed information on smoking history, the main cause of lung cancer.MethodsTo clarify the differences in genetic mutation profiles between Caucasian and Japanese subjects, we compared data from The Cancer Genome Atlas, which mainly included Caucasians, with results from the Japan Molecular Epidemiology for lung cancer study, which is an epidemiological study only involving Japanese subjects. We divided the participants into four groups according to smoking status and performed comparative analysis by tissue type (lung adenocarcinoma and squamous cell lung cancer).ResultsIn patients with lung adenocarcinoma, the frequency of EGFR mutations was lower in Caucasian subjects than in Japanese subjects (14.6% vs. 51.1%), whereas the frequencies of mutations in other genes, namely KRAS (32.9% vs. 9.3%), TP53 (45.2% vs. 20.7%), BRAF (9.6% vs. 1.3%), PIK3CA (5.9% vs. 2.6%), KEAP1 (17.8% vs. 0.5%), NF1 (10.9% vs. 0.5%), STK11 (17.8% vs. 0.7%), RBM10 (8.7% vs. 0.1%), and MET (7.8% vs. 0.1%), were higher in Caucasian subjects. Among patients with squamous cell carcinoma, TP53 (81.2% vs. 49.1%), PIK3CA (14.5% vs. 6.8%), KEAP1 (12.7% vs. 0.9%), and NFE2L2 mutations (15.8% vs. 13.6%) were more common in Caucasian subjects.ConclusionsEthnicity is an important and complex characteristic that must be recognized and considered, even in the era of precision medicine. We should collaborate to share data for different ethnicities and incorporate them into clinical practice and the design of global clinical studies. Carefully designed molecular epidemiological studies focusing on ethnic differences are warranted.
| S-EPMC7399397 | biostudies-literature
Project description:Chronic total occlusions (CTO) in coronary angiographies present a significant challenge nowadays. Intravascular ultrasound (IVUS) is a valuable tool during CTO-PCI, aiding in planning and achieving procedural success. However, the impact of IVUS on clinical and procedural outcomes in CTO-PCI remains uncertain. This meta-analysis aimed to compare IVUS-guided and angiography-guided approaches in CTO-PCI. The study included five studies and 2320 patients with stable coronary artery disease (CAD) and CTO. The primary outcome of major adverse cardiac events (MACE) did not significantly differ between the groups (p = 0.40). Stent thrombosis was the only secondary clinical outcome that showed a significant difference, favoring the IVUS-guided approach (p = 0.01). Procedural outcomes revealed that IVUS-guided procedures had longer stents, larger diameters, and longer procedure and fluoroscopy times (p = 0.007, p < 0.001, p = 0.03, p = 0.002, respectively). Stent number and contrast volume did not significantly differ between the approaches (p = 0.88 and p = 0.33, respectively). In summary, routine IVUS use did not significantly improve clinical outcomes, except for reducing stent thrombosis. Decisions in CTO-PCI should be individualized based on patient characteristics and supported by a multi-parametric approach.
| S-EPMC10419599 | biostudies-literature
Project description:AimThe aim of the study was to evaluate the pharmacokinetics (PK) of inhaled and intravenous (i.v.) fluticasone furoate (FF) in healthy Caucasian, Chinese, Japanese and Korean subjects.MethodThis was an open label, randomized, two way crossover study in healthy Caucasian, Chinese, Japanese and Korean subjects (n = 20 per group). Inhaled FF (200 μg for 7 days, then 800 μg for 7 days from a dry powder inhaler [DPI]) was administered in one treatment period and i.v.FF (250 μg infusion) in the other. FF PK and serum cortisol (inhaled 200 μg only) were compared between the ethnic groups using analysis of variance. P450 CYP3A4 activity and safety were also assessed.ResultsEthnic differences in i.v. FF PK were accounted for by body weight differences. CYP3A4 activity was similar across the groups. Higher FF systemic exposure was seen following inhaled dosing in Chinese, Japanese and Korean subjects compared with Caucasian subjects. Absolute bioavailability was greater (36%-55%) in all East Asian groups than for Caucasian subjects following inhaled FF 800 μg. Deconvolution analysis suggested inhaled FF resided in the lung of East Asian subjects longer than for Caucasians (time for 90% to be absorbed [t90]: 29.1-30.8 h vs. 21.4 h). In vitro simulation method predicted comparable delivered lung dose across ethnic groups. Serum cortisol weighted mean was similar between Caucasians and Chinese or Koreans, while in Japanese was on average 22% lower than in Caucasians. All FF treatments were safe and well tolerated.ConclusionModestly higher (<50%) FF systemic exposure seen in East Asian subjects following inhaled dosing was not associated with a clinically significant effect on serum cortisol, suggesting that a clinical dose adjustment in East Asian subjects is not required.
| S-EPMC4004401 | biostudies-literature
Project description:IntroductionThe functional study of genetic risk factors for Alzheimer's disease (AD) provides insights into the underlying mechanisms and identification of potential therapeutic targets. Investigating AD-associated genetic loci identified in East Asian populations using single-nucleus RNA-sequencing data may identify novel functional genetic contributors.MethodsCell type-specific expression quantitative trait loci (eQTL) and peak-to-gene links were used to identify functional genes associated with 26 genetic loci from seven genome-wide association studies (GWAS) for AD in East Asians.ResultsKCNJ6 and MAPK1IP1L were identified as significant eQTLs with AD risk loci. AD risk loci were in peaks related to four genes, with CLIC4 being connected across different cell types. Genes identified in European and East Asian GWAS interacted within networks and were enriched in AD pathology pathways in astrocytes.DiscussionOur findings suggest KCNJ6 and CLIC4 as novel AD-associated functional genes, providing insight into the genetic architecture of AD in East Asians.HighlightsIntegrated functional analysis of Alzheimer's disease (AD) loci in seven East Asian genome-wide association studies (GWAS) was performed. Cell type-specific expression quantitative trait loci (eQTLs) and assay for transposase-accessible chromatin peaks were used to identify AD functional genes. An AD risk variant was linked to KCNJ6 through an oligodendrocyte progenitor cell-specific eQTL. An AD risk variant maps to open chromatin, linked to CLIC4 across six cell types. Astrocyte differentially expressed genes by AD pathology are enriched in East Asian and European GWAS genes.
| S-EPMC11848548 | biostudies-literature