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- Minimal Adherence Threshold to Non-Vitamin K Antagonist Oral
Anticoagulants in Patients with Atrial Fibrillation to Reduce the Risk of Thromboembolism and Death: A Nationwide Cohort Study-
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Abstract: Purpose Poor adherence to non-vitamin K antagonist oral anticoagulants (NOACs) may raise thromboembolic risks in patients with atrial fibrillation (AF). However, the minimal adherence to maintain the protective effect of NOACs is currently unknown. Therefore, we investigated thresholds of NOAC adherence in association with thromboembolic and mortality risks. Methods Patients with AF initiating NOACs between 2013 and 2019 were identified in Belgian nationwide data. Adherence was measured using the proportion of days covered (PDC) after one year of treatment. Inverse probability of treatment weighted Cox regression was used to investigate outcomes. Results 92,111 persons were included (250,750 person-years). Compared to NOAC users with a one-year PDC of 100%, significantly higher risks of stroke or systemic embolism were observed among NOAC users with PDCs of 85–89% (adjusted hazard ratio (aHR) 1.35, 95% confidence interval (CI) (1.19–1.54)), 80–84% (aHR 1.31, 95%CI (1.08–1.58)) and < 80% (aHR 1.64, 95%CI (1.34–2.01)), while no significant differences were observed among NOAC users with one-year PDCs of 95–99% (aHR 1.02, 95%CI (0.94–1.12)) or 90–94% (aHR 1.06, 95%CI (0.95–1.18)). Significantly higher risks of all-cause mortality were observed with decreasing levels of NOAC adherence, which were already higher among NOAC users with a one-year PDC of 90–94% versus 100% (aHR 1.09, 95%CI (1.01–1.17)). Findings were similar with once-daily and twice-daily dosed NOACs. Conclusion Poor adherence to NOACs is associated with increased risks of thromboembolism and all-cause mortality. The minimal adherence threshold should be ≥ 90%, preferably even ≥ 95%. PubDate: 2023-09-14
- Trimetazidine to Reduce Myocardial Fibrosis—Competing Interests with
SGLT2 Inhibitors'-
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PubDate: 2023-09-13
- Long Non-coding RNA Involved in the Pathophysiology of Atrial Fibrillation
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Abstract: Background Atrial fibrillation (AF) is a prevalent and chronic cardiovascular disorder associated with various pathophysiological alterations, including atrial electrical and structural remodeling, disrupted calcium handling, autonomic nervous system dysfunction, aberrant energy metabolism, and immune dysregulation. Emerging evidence suggests that long non-coding RNAs (lncRNAs) play a significant role in the pathogenesis of AF. Objective This discussion aims to elucidate the involvement of AF-related lncRNAs, with a specific focus on their role as miRNA sponges that modulate crucial signaling pathways, contributing to the progression of AF. We also address current limitations in AF-related lncRNA research and explore potential future directions in this field. Additionally, we summarize feasible strategies and promising delivery systems for targeting lncRNAs in AF therapy. Conclusion In conclusion, targeting AF-related lncRNAs holds substantial promise for future investigations and represents a potential therapeutic avenue for managing AF. PubDate: 2023-09-13
- Evaluation of the Efficacy of Sacubitril/Valsartan on Radiofrequency
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Abstract: Objective To evaluate whether the effect of radiofrequency ablation can be improved by using sacubitril/valsartan (S/V) to control blood pressure in hypertensive patients with persistent atrial fibrillation. Methods A total of 63 and 67 hypertension patients with persistent atrial fibrillation were enrolled in an S/V group and ACEI/ARB group, respectively. All patients underwent radiofrequency catheter ablation (RFCA). The blood pressure of the two groups was controlled within the range of 100–140 mmHg (high pressure) and 60–90 mmHg (low pressure). The clinical outcomes of the two groups were observed after 12 months of follow-up. Results No significant differences in blood pressure were observed between the S/V and ACEI/ARB groups. In addition, the recurrence rate of atrial fibrillation between the two groups was not different. The left atrial diameter was an independent predictor of recurrence (HR = 1.063, P = 0.008). However, in the heart failure subgroup, the recurrence rate of S/V was significantly lower than that of the ACEI/ARB group (P = 0.005), and Cox regression analysis showed that the recurrence risk of atrial fibrillation of the S/V group was 0.302 lower than that of the ACEI/ARB group. NT-proBNP, LVEF, and LAD were significantly improved in hypertension patients with heart failure when comparing cases before and at the end of follow-up. Conclusions S/V is better than ACEI/ARB in reducing the recurrence of persistent atrial fibrillation in patients with hypertension and heart failure after RFCA. PubDate: 2023-09-07
- A Novel Parallel Wire-based Antegrade Dissection Re-entry Technique for
Failed Retrograde Attempt of Coronary Chronic Total Occlusions with Risk Nomogram Analysis-
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Abstract: Background Rapid development in coronary chronic total occlusion (CTO) interventional techniques and devices have achieved a greater success rate with favorable outcomes. Antegrade dissection re-entry (ADR) technique is an important CTO crossing strategy and a desirable approach for long CTOs with good distal landing zone. However, unsuccessful procedures in contemporary CTO-percutaneous coronary intervention (PCI) remain, especially in lesions with non-interventional collaterals. Method Based on a single center experience, a hybrid interventional algorithm, parallel wire-based ADR (PW-ADR) combines the advantages of parallel wire technique (PWT) and device-based ADR to target CTO lesions with failed retrograde approach. A retrospective analysis of patients who underwent PW-ADR was performed. A risk nomogram was created to identify patients at high risk for technical failure. Results A total of 57 patients treated with PW-ADR were ultimately included in the present study. A total of 46 (80.7%) cases achieved technical success and procedural success, with low incidence of in-hospital complications or 1-year major adverse cardiac events (MACE). The risk nomogram identified 3 predictor variables associated with technical failure of PW-ADR, including tortuous vessel, J-CTO score, and times of antegrade coronary angiography (CAG) during ADR, with promising accuracy (AUROC 0.947). Conclusion The novel hybrid CTO-PCI algorithm, PW-ADR, provided an alternative interventional approach for complex CTO lesions with a promising success rate. The risk nomogram served as a prompter for high-risk cases, which may warrant a change in treatment strategy. PubDate: 2023-09-07
- Effects of Rhythm Control for Atrial Fibrillation on Cardiac Remodeling
and Valvular Regurgitation in Patients with Heart Failure-
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Abstract: Purpose Previous studies investigating cardiac remodeling and functional regurgitation of rhythm control for atrial fibrillation (AF) in heart failure (HF) are limited. Therefore, this study aimed to evaluate the impact of rhythm control for AF on cardiac remodeling and functional regurgitation in the spectrum of HF. Its effect on prognosis was explored. Methods According to the treatment strategies of AF, the cohort was classified into the rhythm control and rate control groups. To further detect the implications of rhythm control on cardiac remodeling, functional regurgitation, and outcomes in HF subtypes, patients were further divided into HF with reduced ejection fraction (HFrEF), HF with mildly reduced ejection fraction, and HF with preserved ejection fraction (HFpEF) subgroups. Results A total of 828 patients were enrolled, with 307 patients in the rhythm control group and 521 patients in the rate control group. Over a median follow-up time of 3.8 years, patients with rhythm control treatments experienced improvements in biatrial structure parameters, left ventricular ejection fraction, and functional regurgitation (mitral and tricuspid regurgitation) compared with rate control treatment (p < 0.05). Cox regression analysis demonstrated that rhythm control reduced the risks of all-cause mortality (HR 0.436 [95% CI, 0.218–0.871], p = 0.019) in HFpEF and HF-related admissions in HFrEF (HR 0.500 [95% CI, 0.330–0.757], p = 0.001) and HFpEF (HR 0.541 [95% CI, 0.407–0.720], p < 0.001); these associations were similar after adjusting for multiple confounders. Conclusions Rhythm control therapy can be considered an appropriate treatment strategy for the management of AF in HF to improve cardiac remodeling, functional regurgitation, and prognosis. PubDate: 2023-08-30
- Pulmonary Circulation Under Pressure: Pathophysiological and Therapeutic
Implications of BK Channel-
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Abstract: Abstract The large-conductance Ca2+-activated K+ (BK) channel is widely expressed in the pulmonary blood vessels and plays a significant role in regulating pulmonary vascular tonus. It opens under membrane depolarization, increased intracellular Ca+2 concentration, and chronic hypoxia, resulting in massive K+ efflux, membrane hyperpolarization, decreased L-type Ca+2 channel opening, and smooth muscle relaxation. Several reports have demonstrated an association between BK channel dysfunction and pulmonary hypertension (PH) development. Decreased BK channel subunit expression and impaired regulation by paracrine hormones result in decreased BK channel opening, increased pulmonary vascular resistance, and pulmonary arterial pressure being the cornerstone of PH. The resulting right ventricular pressure overload ultimately leads to ventricular remodeling and failure. Therefore, it is unsurprising that the BK channel has arisen as a potential target for treating PH. Recently, a series of selective, synthetic BK channel agonists have proven effective in attenuating the pathophysiological progression of PH without adverse effects in animal models. PubDate: 2023-08-25
- Exercise Prevents Glucocorticoid-Induced Myocardial 4-Hydroxynonenal
Production-
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Abstract: Purpose Long-term administration of glucocorticoids (GCs) increases myocardial oxidative stress. 4-Hydroxynonenal (4-HNE) protein adducts, a marker of oxidative damage, have been associated with several cardiovascular diseases, including atherosclerosis, cardiac hypertrophy, cardiomyopathy, and ischemia–reperfusion injury. Exercise training has been shown to have a protective effect on the heart by lowering the level of oxidative stress in cardiomyocytes. Therefore, we aimed to investigate the effect of long-term dexamethasone treatment and exercise training on myocardial 4-HNE levels. Methods Twenty-four female Wistar albino rats were assigned to sedentary control-saline treated (C, n = 8), sedentary-dexamethasone treated (D, n = 8), and exercise training-dexamethasone treated (DE, n = 8) groups. Daily dexamethasone was injected for 28 days at a 1 mg kg−1 dose, while C animals were injected with the same volume of saline subcutaneously. DE animals underwent an exercise training protocol of 60 min/day, 5 days a week, at 25 m/min−1 (0% grade) for 28 days. Left ventricular 4-HNE, Hsp72 levels, and pHsp25/Hsp25 ratio were determined by Western blot. Results The administration of dexamethasone led to a significant elevation in 4-HNE levels in the myocardium of adult rats (p < 0.05; D vs. C). The concurrent implementation of exercise training impeded this increase (p > 0.05; DE vs. C). Exercise training induced a threefold increase in myocardial Hsp72 expression (p < 0.001; DE vs. C and D) and attenuated the dexamethasone-induced increase in Hsp25 phosphorylation (p < 0.05; C vs. D) (p < 0.001; DE vs. D). Conclusion Our results indicate that long-term administration of dexamethasone is associated with an increase in cardiac 4-HNE levels, which is hindered by the addition of exercise training. PubDate: 2023-08-25
- Does Genotype Affect the Efficacy of PCSK9 Inhibitors in the Treatment of
Familial Hypercholesterolemia'-
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Abstract: Purpose of Review This review discusses whether patients’ genotype affects the efficacy of PCSK9 inhibitors in treating familial hypercholesterolemia and how this might influence clinical management. Recent Findings Currently, available evidence consistently demonstrates and is in good agreement that, in general, the LDL-C-lowering effect of PCSK9 inhibitors is similar across genotypes, except for compound heterozygous and homozygous familial hypercholesterolemia (FH). However, it remains to be seen whether the comparable therapeutic effect in lowering LDL-C level also leads to a comparable degree of cardiovascular risk reduction with different genotypes. Summary Generally, the level of LDL-C reduction following PCSK9 inhibitor treatment is similar within different genotypes. Hence, genotype is a less reliable predictor for further LDL-C level reduction on PCSK9 inhibitor therapy, and attention should be given to other external influences, especially for heterozygous FH. PubDate: 2023-08-23
- PDHA1 Alleviates Myocardial Ischemia-Reperfusion Injury by Improving
Myocardial Insulin Resistance During Cardiopulmonary Bypass Surgery in Rats-
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Abstract: Objective Cardiopulmonary bypass (CPB) is a requisite technique for thoracotomy in advanced cardiovascular surgery. However, the consequent myocardial ischemia-reperfusion injury (MIRI) is the primary culprit behind cardiac dysfunction and fatal consequences post-operation. Prior research has posited that myocardial insulin resistance (IR) plays a vital role in exacerbating the progression of MIRI. Nonetheless, the exact mechanisms underlying this phenomenon remain obscure. Methods We constructed pyruvate dehydrogenase E1 α subunit (PDHA1) interference and overexpression rats and used ascending aorta occlusion in an in vivo model of CPB-MIRI. We devised an in vivo model of CPB-MIRI by constructing rat models with both pyruvate dehydrogenase E1α subunit (PDHA1) interference and overexpression through ascending aorta occlusion. We analyzed myocardial glucose metabolism and the degree of myocardial injury using functional monitoring, biochemical assays, and histological analysis. Results We discovered a clear downregulation of glucose transporter 4 (GLUT4) protein content expression in the CPB I/R model. In particular, cardiac-specific PDHA1 interference resulted in exacerbated cardiac dysfunction, significantly increased myocardial infarction area, more pronounced myocardial edema, and markedly increased cardiomyocyte apoptosis. Notably, the opposite effect was observed with PDHA1 overexpression, leading to a mitigated cardiac dysfunction and decreased incidence of myocardial infarction post-global ischemia. Mechanistically, PDHA1 plays a crucial role in regulating the protein content expression of GLUT4 on cardiomyocytes, thereby controlling the uptake and utilization of myocardial glucose, influencing the development of myocardial insulin resistance, and ultimately modulating MIRI. Conclusion Overall, our study sheds new light on the pivotal role of PDHA1 in glucose metabolism and the development of myocardial insulin resistance. Our findings hold promising therapeutic potential for addressing the deleterious effects of MIRI in patients. PubDate: 2023-08-23
- High BMI: Another Barrier to Rapid Platelet Inhibition After STEMI PCI
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PubDate: 2023-08-18
- Effect of Beta-Blocker on Long-Term Major Cardiovascular Events in High
Atherosclerotic Risk Population-
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Abstract: Purpose Beta-blocker is a frequently used medication in cardiovascular diseases. However, long-term benefit of beta-blocker in patients with preserved left ventricular ejection function (LVEF) on major adverse cardiovascular events (MACEs) is uncertain. Methods The Cohort Of patients with high Risk for cardiovascular Events (CORE-Thailand) was a prospective study that enrolled Thai patients with high atherosclerotic risk including multiple atherosclerotic risk factors and established atherosclerotic cardiovascular diseases. Baseline demographic data, co-morbidities and medication were recorded. Patients were followed for 5 years. Patients with LVEF<50% were excluded. Primary outcome was the effect of beta-blocker on the occurrence of MACEs including all-cause death, non-fatal myocardial infarction and non-fatal stroke (3P-MACEs). Propensity score matching was used to control confounding factors. Results There was a total of 8513 patients in the pre-matched cohort, 4418 were taking beta-blocker and 4095 were not. After adjustment of confounders, beta-blocker was an independent predictor of 3P-MACEs (adjusted HR 1.29;95% CI 1.12-1.49;p<0.001). After propensity score matching, 4686 patients remained in the post-matched cohort. Propensity score analysis showed consistent results in which patient taking beta-blocker had higher risk of 3P-MACEs (adjusted HR 1.29;95% CI 1.10-1.53;p=0.002). Subgroup analysis in patients with coronary artery disease (CAD) indicated that taking beta-blocker did not increase the incidence of 3P-MACEs (adjusted HR 0.99;95% CI 0.76-1.29) while those without CAD did (adjusted HR 1.51; 95% CI, 1.22-1.86;p-interaction=0.015). Conclusion In patients with high atherosclerotic cardiovascular risk, taking beta-blockers had a higher risk of 3P-MACEs. Care should be taken when prescribing beta-blockers to patients without a clear indication. Trial registration TCTR20130520001 registered in Thai Clinical Trials Registry (TCTR) https://www.thaiclinicaltrials.org/, date of registration 20 May 2013. PubDate: 2023-08-18
- US Population Eligibility and Estimated Impact of Semaglutide Treatment on
Obesity Prevalence and Cardiovascular Disease Events-
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Abstract: Background Semaglutide 2.4 mg benefits weight loss and reduction of cardiovascular disease (CVD) risk factors in adults with obesity. We estimated the US population eligibility for semaglutide 2.4 mg (based on the weight management indication) and the impact on obesity and CVD events. Methods We applied STEP 1 trial eligibility criteria to US adults aged ≥ 18 years in the US National Health and Nutrition Examination Survey (NHANES) 2015-2018 to estimate the US eligible population. Semaglutide weight changes in STEP 1 were applied to estimate the population impact on weight changes and obesity prevalence. We also estimated 10-year CVD risks utilizing the BMI-based Framingham CVD risk scores. The difference in estimated risks with and without semaglutide “treatment” multiplied by the eligible NHANES weighted population represented the estimated “preventable” CVD events. Results We identified 3999 US adults weighted to an estimated population size of 93.0 million [M] (38% of US adults) who fit STEP 1 eligibility criteria. Applying STEP 1 treatment effects on weight loss resulted in an estimated 69.1% (64.3 M) and 50.5% (47.0 M) showing ≥ 10% and ≥ 15% weight reductions, respectively, translating to a 46.1% (43.0 M) reduction in obesity (BMI ≥ 30 kg/m2) prevalence. Among those without CVD, estimated 10-year CVD risks were 10.15% “before” and 8.34% “after” semaglutide “treatment” reflecting a 1.81% absolute (and 17.8% relative) risk reduction translating to 1.50 million preventable CVD events over 10 years. Conclusion Semaglutide treatment in eligible US adults may substantially reduce obesity prevalence and CVD events, which may dramatically impact associated healthcare costs. PubDate: 2023-08-14
- Antiphospholipid Syndrome: State of the Art of Clinical Management
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Abstract: Abstract Antiphospholipid syndrome (APS) is a systemic autoimmune disorder clinically characterized by recurrent arterial and venous thrombosis and/or pregnancy morbidity in the presence of antiphospholipid antibodies. Currently, treatment is mainly focused on anticoagulation, but therapies targeting mechanisms involved in APS autoimmune pathogenesis could play an important role in specific settings. An evidence-based therapeutic approach is limited by the broad clinical spectrum of the syndrome and the nature of a “rare disease” that makes it difficult to carry out well-designed prospective studies. Vitamin K antagonists (AVK), notably warfarin, are the standard treatment for preventing recurrent venous thrombosis and perhaps also arterial thrombosis. Direct oral anticoagulants (DOACs) are not recommended at least in patients with triple positivity APS. Treatment options for the prevention of pregnancy complications in obstetric APS, as combined use of aspirin and heparin, low-dose prednisolone, hydroxychloroquine, intravenous immunoglobulin (IVIG), may improve pregnancy outcome. The catastrophic antiphospholipid syndrome (CAPS) is the most severe form of APS with acute multiple organ involvement and small vessel thrombosis. Glucocorticoids, heparin, plasma exchange or IVIG, rituximab, or eculizumab must be added to concurrent treatment of precipitating factors (e.g. infections) as rescue therapies. Finally, it has been observed that SARS COV2 infection may produce vascular complications mimicking the clinical and pathophysiological features of APS and particularly of CAPS. From this point of view, attention has been focused on the “protective” role of anticoagulant therapy in preventing thrombotic complication when these clinical conditions coexist. PubDate: 2023-08-12
- Beneficial Effects of Angiotensin II Receptor Blockers on Mortality in
Patients with COVID-19: A Retrospective Study from 2019 to 2020 in China-
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Abstract: Background The COVID-19 pandemic has become a serious global public health problem. Although the use of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor type 1 blockers (ARBs) has been recommended in patients with COVID-19 and cardiovascular diseases (CVDs), according to the results of some small-sample retrospective analyses, there remains a lack of sufficient evidence to validate their efficacy. This multicenter retrospective study investigated whether ACEI/ARB administration was beneficial in patients with COVID-19 and CVDs. Methods A total of 11,231 patients with confirmed COVID-19 and CVDs, from 138 hospitals in Hubei Province, were included in this multicenter retrospective study. We compared the clinical characteristics and outcomes between the ARB and non-ARB groups and analyzed the risk factors for in-hospital death using univariate and multivariate Cox regression analyses and Kaplan–Meier curves. Results In the multivariate Cox regression model, after adjusting for age, gender, comorbidities, and in-hospital medications, ARB use was associated with lower all-cause mortality (adjusted HR, 0.53; 95% CI, 0.38–0.73; P < 0.001). After propensity score-matched analysis, the adjusted HR for the use of ARB associated with all-cause mortality was 0.62 (95% CI, 0.40–0.88; P = 0.02). Further subgroup analyses found that the adjusted HRs for the use of ARB associated with all-cause mortality were 0.52 (95% CI, 0.30–0.89; P = 0.016), 0.37 (95% CI, 0.21–0.64; P < 0.001), 0.42 (95% CI, 0.28–0.64; P < 0.001), and 0.55 (95% CI, 0.37–0.84; P = 0.005) in patients with heart failure, diabetes, and hypercholesterolemia, and severe COVID-19, respectively. Conclusions ARB administration was significantly associated with a lower risk of all-cause mortality in patients with COVID-19 and CVDs. Trial registration ClinicalTrials.gov NCT05615792. https://www.clinicaltrials.gov/ct2/show/NCT05615792 PubDate: 2023-08-11
- Direct Oral Anticoagulants: Navigating Through Clinical Challenges
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Abstract: Purpose Direct oral anticoagulants (DOACs) have been approved, for over a decade, by both European and American medicine agencies, for treatment and prevention of several cardiovascular conditions. Since then, an increasing amount of data has been added to the medical literature day by day, resulting in a dichotomy in selection of the appropriate agent, dosage, and duration of treatment for special populations with multiple comorbidities. Considering these issues, we have prepared a comprehensive review for the clinical practitioner, to optimize the DOAC utilization in clinical practice. Methods A thorough literature search and review was conducted, concerning mainly the last decade. Our review focused on the current guidelines and the most recently published studies in PubMed, Science Direct Scopus, and Google Scholar to date. Conclusion The purpose of this study is to provide guidance for healthcare professionals for making proper decisions when confronted with clinical challenges. Nevertheless, further research is required to establish DOAC superiority in complicated cases, where there is clinical uncertainty. PubDate: 2023-08-08
- Iron Status Screening in Individuals with Heart Failure Before Initiating
Sodium-Glucose Cotransporter 2 Inhibitor Therapy: Is It Necessary'-
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PubDate: 2023-08-07
- Mutant CYP3A4/5 Correlated with Clinical Outcomes by Affecting Rivaroxaban
Pharmacokinetics and Pharmacodynamics in Patients with Atrial Fibrillation -
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Abstract: Purpose This study was designed to investigate the impact of single-nucleotide polymorphism-encoded cytochrome P450 enzymes (CYP3A4/5) on clinical outcomes of rivaroxaban in patients with non-valvular atrial fibrillation (NVAF) based on pharmacokinetics and pharmacodynamics (PK/PD) aspects. Method A prospective study enrolling 165 rivaroxaban-treated patients with NVAF was conducted. Genotyping of CYP3A4 (rs2242480, rs2246709, rs3735451, and rs4646440) and CYP3A5 (rs776746) was performed to explore their impact on the trough plasma concentrations (Ctrough) of rivaroxaban, coagulation indicators at the Ctrough including activated partial thromboplastin time (APTT) and prothrombin time (PT), and clinical outcomes. Results Patients with mutant genotype CYP3A4 (rs2242480, rs2246709, and rs3735451) and CYP3A5 (rs776746) had higher levels of rivaroxaban Ctrough, PT values than that of wild-type. Furthermore, a positive relationship was revealed between Ctrough and PT (r = 0.212, p = 0.007), while no significant correlation was found between Ctrough and APTT. Regarding the clinical outcomes, the minor allele carriers on rs3735451 and the minor allele (A) carriers on rs2246709 were associated with higher incidence of minor bleeding (p = 0.028 and p = 0.038, respectively) and were identified as the independent risk factors of minor bleeding treated with rivaroxaban (p = 0.024 and p = 0.036, respectively), with the receiver operating characteristic (ROC) curve validated (AUC = 0.8956, 95% CI: 0.829–0.962). Conclusion The CYP3A4 polymorphisms (rs2242480, rs2246709, and rs3735451) and CYP3A5 rs776746 were associated with variations in rivaroxaban PK/PD. The minor allele (C) carriers on rs3735451 and the minor allele (A) carriers on rs2246709 were correlated with clinical outcomes. PubDate: 2023-08-05
- P2Y12 Inhibitors in STEMI Patients — One Size Does Not Fit All
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PubDate: 2023-08-02
- Surgical or Percutaneous Coronary Revascularization for Heart Failure: a
Focus on Symptoms and Stenosis-
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PubDate: 2023-08-01
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