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BACKGROUND: Various genetic and nongenetic variables influence the high on-treatment platelet reactivity (HTPR) in patients taking clopidogrel. AIM: This study aimed to develop a novel machine learning (ML) model to predict HTPR in Chinese patients after percutaneous coronary intervention (PCI). METHOD: This cohort study collected information on 507 patients taking clopidogrel. Data were randomly divided into a training set (90%) and a testing set (10%). Nine candidate Machine learning (ML) models and multiple logistic regression (LR) analysis were developed on the training set. Their performance was assessed according to the area under the receiver operating characteristic curve, precision, recall, F1 score, and accuracy on the test set. Model interpretations were generated using importance scores by transforming model variables into scaled features and representing in radar plots. Finally, we established a prediction platform for the prediction of HTPR. RESULTS: A total of 461 patients (HTPR rate: 19.52%) were enrolled in building the prediction model for HTPR. The XGBoost model had an optimized performance, with an AUC of 0.82, a precision of 0.80, a recall of 0.44, an F1 score of 0.57, and an accuracy of 0.87, which was superior to those of LR. Furthermore, the XGBoost method identified 7 main predictive variables. To facilitate the application of the model, we established an XGBoost prediction platform consisting of 7 variables and all variables for the HTPR prediction. CONCLUSION: A ML-based approach, such as XGBoost, showed optimum performance and might help predict HTPR on clopidogrel after PCI and guide clinical decision-making. Further validated studies will strengthen this finding.
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Clopidogrel , Pueblos del Este de Asia , Intervención Coronaria Percutánea , Humanos , Clopidogrel/farmacología , Estudios de Cohortes , Inhibidores de Agregación Plaquetaria/farmacología , Aprendizaje AutomáticoRESUMEN
Background: Venous thromboembolism (VTE) is a common cardiovascular disease that seriously threatens human lives. Anticoagulant therapy is considered to be the cornerstone of VTE treatment. An increasing number of studies has been updated in the VTE anticoagulation field. However, no bibliometric analyses have assessed these publications comprehensively. Therefore, our study aimed to analyze the global status, hotspots, and trends of anticoagulant therapy for VTE. Methods: The relevant literature on VTE anticoagulation published between 2012 and 2021 was retrieved and collected from the Web of Science Core Collection database. VOSviewer, Cooccurrence Matrix Builder, gCLUTO, and some online visualization tools were adopted for bibliometric analysis. Results: A total of 15,152 related articles were retrieved. In recent years, the research output of VTE anticoagulation gradually increased. The United States was the most productive country. International cooperation is concentrated in North America and Europe; the most influential documents, journals, authors, and organizations were also from these two continents. Research hotspots mainly focus on clinical guidelines, VTE in special populations, non-vitamin K oral anticoagulants (NOACs), and parenteral anticoagulation. The research frontiers and trends include the assessment of NOACs and the antithrombotic management of VTE complicated with coronavirus disease 2019 (COVID-19). Conclusion: This bibliometric analysis provides a systematic overview of the VTE anticoagulation research, which will facilitate researchers to better understand the situation of VTE anticoagulation. Future studies should be dedicated to NOACs application and VTE-combined COVID-19 patients.
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COVID-19 , Tromboembolia Venosa , Humanos , Administración Oral , Anticoagulantes/uso terapéutico , COVID-19/complicaciones , Tromboembolia Venosa/tratamiento farmacológico , Tromboembolia Venosa/prevención & control , Tromboembolia Venosa/etiología , Vitamina K/uso terapéutico , BibliometríaRESUMEN
BACKGROUND: Atrial fibrillation (AF) is a common arrhythmia that requires anticoagulation therapy to prevent stroke. However, there is still a significant under-/over-treatment in stroke prevention for patients with AF. The adherence and the risk of bleeding associated with oral anticoagulation therapy (OACs) are major concerns. Shared decision-making (SDM) is an approach that involves patients and healthcare providers in making decisions about treatment options. This study aims to assess the effectiveness of a novel SDM tool for anticoagulation management in AF. METHODS: The study will be a prospective, cluster randomized controlled trial involving 440 patients with AF in 8 community health service centers (clusters) in Shanghai, China. The SDM group will receive anticoagulation management through the novel SDM tool, while the control group will receive standard care. The follow-up period will be at least 2 years. The primary outcome will be any bleeding event, while secondary outcomes include the accordance of stroke prophylaxis for AF according to the current guidelines, time in therapeutic range (TTR), the occurrences of major bleeding and thrombosis events, and patient knowledge, adherence, and satisfaction. DISCUSSION: This study will provide evidence of the effectiveness of shared decision-making in improving the appropriateness of OAC use in Chinese AF patients. The findings may inform the development of guidelines and policies for the management of AF and anticoagulation therapy in China and other countries. TRIAL REGISTRATION: ChiCTR ChiCTR2200062123. Registered on 23 July 2022.
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Fibrilación Atrial , Accidente Cerebrovascular , Humanos , Fibrilación Atrial/complicaciones , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/tratamiento farmacológico , Anticoagulantes/efectos adversos , Estudios Prospectivos , China , Accidente Cerebrovascular/prevención & control , Accidente Cerebrovascular/complicaciones , Hemorragia/inducido químicamente , Hemorragia/tratamiento farmacológico , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
BACKGROUND: Direct oral anticoagulants (DOACs) are increasingly recommended over warfarin in stroke prevention for patients with non-valvular atrial fibrillation (AF). However, there is an important evidence gap in choosing the most appropriate DOAC for Chinese patients in clinical practice. METHODS: A multi-criteria decision analysis (MCDA) was adopted to build a scoring framework. Attributes and criteria were identified and determined by a scoping literature review, two rounds of Delphi surveys, and a consensus meeting. Weights of each attribute and criterion in the framework were determined using analytic hierarchy process (AHP). Evidence was collected based on the domestic or at least Asian data. Scoring methods for each criterion were developed depended on their characteristics and determined with an expert consensus meeting. Comprehensive scores of each DOAC were calculated based on the utility scores of each criterion and their corresponding weights. RESULTS: A total of 5 attributes, including safety, efficacy, costs/cost-effectiveness, suitability, and accessibility, were determined, and 16 criteria were under the 5 attributes. The safety and efficacy were ranked as the top two important attributes with the weights of 38.8% and 35.9%, respectively, while the suitability received the lowest weight of 7.9%. The comprehensive score for edoxaban was the highest (72.3), followed by dabigatran (49.7), rivaroxaban (37.9), and apixaban (35.8). CONCLUSIONS: This study provided a scoring framework developed for comprehensive evaluation of DOACs in China. The ranking of DOACs could help to support the decision-making in clinical practice. The framework could provide a reference for comprehensive evaluation of other drugs.
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Fibrilación Atrial , Accidente Cerebrovascular , Humanos , Fibrilación Atrial/complicaciones , Fibrilación Atrial/tratamiento farmacológico , Anticoagulantes/uso terapéutico , Accidente Cerebrovascular/prevención & control , Accidente Cerebrovascular/tratamiento farmacológico , Warfarina/uso terapéutico , Rivaroxabán/uso terapéutico , Dabigatrán/uso terapéutico , Piridonas/uso terapéutico , Administración OralRESUMEN
BACKGROUND: The accuracy of current prediction tools for venous thromboembolism (VTE) events following hernia surgery remains insufficient for individualized patient management strategies. To address this issue, we have developed a machine learning (ML)-based model to dynamically predict in-hospital VTE in Chinese patients after hernia surgery. METHODS: ML models for the prediction of postoperative VTE were trained on a cohort of 11â 305 adult patients with hernia from the CHAT-1 trial, which included patients across 58 institutions in China. In data processing, data imputation was conducted using random forest (RF) algorithm, and balanced sampling was done by adaptive synthetic sampling algorithm. Data were split into a training cohort (80%) and internal validation cohort (20%) prior to oversampling. Clinical features available pre-operatively and postoperatively were separately selected using the Sequence Forward Selection algorithm. Nine-candidate ML models were applied to the pre-operative and combined datasets, and their performance was evaluated using various metrics, including area under the receiver operating characteristic curve (AUROC). Model interpretations were generated using importance scores, which were calculated by transforming model features into scaled variables and representing them in radar plots. RESULTS: The modeling cohort included 2856 patients, divided into 2536 cases for derivation and 320 cases for validation. Eleven pre-operative variables and 15 combined variables were explored as predictors related to in-hospital VTE. Acceptable-performing models for pre-operative data had an AUROC ≥ 0.60, including logistic regression, support vector machine with linear kernel (SVM_Linear), attentive interpretable Tabular learning (TabNet), and RF. For combined data, logistic regression, SVM_Linear, and TabNet had better performance, with an AUROC ≥ 0.65 for each model. Based on these models, 7 pre-operative predictors and 10 combined predictors were depicted in radar plots. CONCLUSIONS: A ML-based approach for the identification of in-hospital VTE events after hernia surgery is feasible. TabNet showed acceptable performance, and might be useful to guide clinical decision making and VTE prevention. Further validated study will strengthen this finding.
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Hernia Inguinal , Tromboembolia Venosa , Adulto , Humanos , Hernia Inguinal/cirugía , Algoritmos , Hospitales , Aprendizaje AutomáticoRESUMEN
PURPOSE: Appropriate prescription of oral anticoagulants (OACs) and good patient adherence are essential to ensure optimal anticoagulation in patients with atrial fibrillation (AF). The aim of this study is to develop a mobile health tool to aid both clinicians and patients with AF in anticoagulation therapy. METHODS: In this study, a novel anticoagulation management model integrating decision support and patient follow-up, the I-Anticoagulation, was developed based on a WeChat Mini Program. With this tool, the risks of stroke and bleeding in AF patients can automatically be calculated according to their characteristics. Anticoagulation regimens were recommended based on a trade-off analysis that balances stroke and bleeding risks according to recent clinical guidelines. A shared decision can be made with full communication between medical professionals and patients. Moreover, follow-up was also conducted using I-Anticoagulation. RESULTS: A total of 120 AF patients receiving anticoagulants (40 received warfarin and 80 received non-vitamin K antagonist oral anticoagulants [NOACs]) were included in the pilot study. The incidence of thromboembolic events was 2.5% and 1.3%, and the rates of bleeding events were 22.5% and 13.8% in the warfarin and NOAC groups, respectively. Generally, self-reported adherence was high, and the satisfaction with anticoagulation was good in all patients with AF. CONCLUSION: Overall, the anticoagulation management model developed in this study could be involved in the full process of anticoagulation therapy in AF patients to improve rationality, adherence, and satisfaction in both medical professionals and patients. However, the usability, feasibility, and acceptability of the I-Anticoagulant-based anticoagulation management model need to be further assessed through well-designed random clinical trials.
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Anticoagulantes/uso terapéutico , Fibrilación Atrial/tratamiento farmacológico , Sistemas de Apoyo a Decisiones Clínicas/instrumentación , Hemorragia/inducido químicamente , Accidente Cerebrovascular/prevención & control , Factores de Edad , Anciano , Anciano de 80 o más Años , Anticoagulantes/administración & dosificación , Anticoagulantes/efectos adversos , Comunicación , Comorbilidad , Estudios de Factibilidad , Femenino , Conductas Relacionadas con la Salud , Humanos , Masculino , Persona de Mediana Edad , Participación del Paciente , Proyectos Piloto , Relaciones Profesional-Paciente , Medición de Riesgo , TelemedicinaRESUMEN
BACKGROUND: The CHA2DS2-VASc score is a guideline-recommended stroke risk stratification scheme for patients with atrial fibrillation (AF). Accurately calculating the CHA2DS2-VASc score and recognizing the stroke risk in AF patients is the foundation of optimal anticoagulation therapy. This survey aims to obtain a comprehensive understanding of perceptions and knowledge gaps on CHA2DS2-VASc scores among Chinese medical professionals for future education programs. METHODS: A cross-sectional survey was conducted among clinicians, including cardiologists, neurologists, emergency physicians (EPs), general practitioners (GPs) and clinical pharmacists (CPs) using a self-administered questionnaire on the Chinese mainland. The survey contained 21 questions in combination with single-choice questions, multiple-choice questions, and an open-ended question, which was distributed online via e-mail or social media. RESULTS: A total of 562 participants (40.9% cardiologists, 19.2% neurologists, 8.5% EPs, 10.3% GPs, and 21.0% CPs) completed the survey. Most respondents across all specialties reported skills requiring improvements in the CHA2DS2-VASc score. In general, cardiologists, neurologists, and CPs had a relatively better understanding than GPs and EPs about the application of CHA2DS2-VASc score. Considering 'H' and 'D' components, more than 90% of respondents chose the correct answer in single-choice questions, whereas the correctness rate declined concerning detailed scoring criteria. Regarding 'C,' 'A2,' 'S2,' and 'V' components, partly correct answers were commonly observed in most multiple-choice questions. The majority of cardiologists believed themselves to be very familiar or at least familiar with the score and its components, while around 70% of EPs and GPs felt relatively unfamiliar with the CHA2DS2-VASc score. Mobile apps, AF guidelines and notebooks/handbooks were popular referencing scoring tools for respondents. CONCLUSIONS: Chinese medical professionals, especially EPs and GPs, revealed a lack of knowledge and insufficient skills for CHA2DS2-VASc scores and their components. Improvements in the awareness of the CHA2DS2-VASc score and its detailed scoring criteria are urgently needed for Chinese medical professionals. Therefore, education programs concerning the introduction of stroke risk evaluation for AF patients and the development of referencing scoring tools are necessary.
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Fibrilación Atrial , Accidente Cerebrovascular , China , Estudios Transversales , Humanos , Farmacéuticos , Medición de Riesgo , Factores de Riesgo , Accidente Cerebrovascular/prevención & control , Encuestas y CuestionariosRESUMEN
Background: The best anticoagulation choice for patients undergoing transcatheter aortic valve replacement (TAVR) with indications of oral anticoagulation (OAC) remains uncertain. We carried out a comprehensive analysis adopting updated evidence that investigated the efficacy and safety of direct oral anticoagulants (DOACs) versus vitamin K antagonists (VKAs) in this population. Methods: A systematic search has been conducted through PubMed, Embase, and Cochrane Library to collect randomized controlled trials (RCTs) and real-world studies comparing the therapy outcomes of DOACs with VKAs in patients undergoing TAVR with indications of OAC up to Dec 2021. Included studies reported all-cause mortality, bleeding, stroke, or composite endpoint. A random-effects model was used and followed a sensitivity analysis based on the heterogeneity. In addition, five scenario analyses were performed to robust our findings. Results: Our analysis included 11 articles enrolling a total of 8934 patients undergone TAVR with indications of OAC (DOACs group = 3890, VKAs group = 5044). Pooled analysis revealed no significant different risk of all-cause mortality (aHR: 0.95, 95% CI: 0.65-1.39, I 2 : 90.6%), stroke (aHR: 0.86, 95% CI: 0.55-1.35, I 2 : 44.3%), bleeding (aHR: 0.83, 95% CI: 0.61-1.13, I 2 : 76.3%), and composite endpoint (aHR: 1.05, 95% CI: 0.88-1.24, I 2 : 11.7%) in the DOACs and VKAs groups. Various forms of death, stroke and bleeding, including cardiovascular death (aHR: 0.92, 95% CI: 0.64-1.33, I 2 : 34.1%), hemorrhagic stroke (aHR: 0.63, 95% CI: 0.23-1.75, I 2 : 22.7%), ischemic stroke (aHR: 0.79, 95% CI: 0.56-1.15, I 2 : 0.0%), transient ischemic attack (aHR: 0.75, 95% CI: 0.40-1.41, I 2 : 0.0%), major or life-threatening bleeding (aHR: 0.96, 95% CI: 0.74-1.24, I 2 : 27.9%), and minor bleeding (aHR: 0.90, 95% CI: 0.52-1.57, I 2 : 54.3%), also showed similar rates among DOACs and VKAs groups. The results based on five scenarios confirmed the said findings. Conclusions: Compared with VKAs, the efficacy and safety of DOACs were comparable for treating TAVR patients combined with anticoagulation indications. Further large-scale RCTs investigating more detailed scenarios are still needed to confirm the optimal anticoagulation strategy.
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The populations included in the randomized controlled clinical trials and observational studies were different. The effectiveness and safety of rivaroxaban for stroke prevention in patients with atrial fibrillation (AF) varied among studies. This study aimed to estimate the real-world outcomes of rivaroxaban in patients with AF accurately. A discrete event simulation (DES) was used to predict the counterfactual results of the ROCKET AF study. The hypothetical cohorts of patients were generated using Monte Carlo simulation according to the baseline covariate distributions that matched the marginal distribution of covariates reported in the ROCKET AF and three observational studies. The DES model structure was constructed based on a priori knowledge about disease progression and possible outcomes of patients with AF. The DES model accurately replicated the overall results of the ROCKET AF study. Both predicted stroke/systematic embolism (SE) and major bleeding rates were lower in the three observational studies than in the simulated ROCKET AF study. The risk difference of stroke/SE and major bleeding was not significant among the predicted outcomes of the three observational studies. Although some differences existed in the absolute rates of stroke/SE and major bleeding between observed and simulated studies, the results confirmed that rivaroxaban was noninferior to warfarin for the prevention of stroke/systematic embolism with no significance in the risk of major bleeding in large AF populations, which was similar to the results of ROCKET AF.
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Fibrilación Atrial , Simulación por Computador , Embolia , Accidente Cerebrovascular , Anticoagulantes/efectos adversos , Fibrilación Atrial/complicaciones , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/tratamiento farmacológico , Inhibidores del Factor Xa/efectos adversos , Humanos , Método de Montecarlo , Estudios Observacionales como Asunto , Ensayos Clínicos Controlados Aleatorios como Asunto , Rivaroxabán/efectos adversos , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/etiología , Resultado del Tratamiento , WarfarinaRESUMEN
Background: Venous thromboembolism (VTE) is highly prevalent in cancer patients. Recent guidelines recommend considering direct oral anticoagulants (DOACs) for the treatment of cancer-associated thrombosis (CAT). However, direct head-to-head comparisons among DOACs are lacking, and almost no net clinical benefit (NCB) analysis has been performed in patients with CAT. Methods: We systematically searched PubMed, EMBASE, Cochrane Library, and ClinicalTrials.gov for randomized controlled trials (RCTs) reporting on recurrent VTE, major bleeding, or clinically relevant bleeding events in patients with CAT who received DOACs and low-molecular-weight heparins. Relative risks (RRs) and 95% confidence intervals (95% CIs) were calculated using a random-effect model. Surface under the cumulative ranking curve (SUCRA) values were calculated, and a trade-off analysis was performed to estimate the NCB. Results: Overall, four RCTs involving 2,894 patients were enrolled. DOACs were more effective than dalteparin in reducing the risk of recurrent VTE (RR: 0.62, 95% CI: 0.44-0.87), with a comparative risk of major bleeding (RR: 1.33, 95% CI: 0.84-2.11) and an increased risk of clinically relevant bleeding (RR: 1.45, 95% CI: 1.05-1.99). No significant difference was observed among individual anticoagulants in terms of recurrent VTE and major bleeding. With respect to the ranking of each anticoagulant for the primary outcome, edoxaban (SUCRA: 69.2) was more effective than dalteparin (SUCRA: 60.7), rivaroxaban (SUCRA: 60.7), and apixaban (SUCRA: 25.5) in reducing VTE recurrence. For major bleeding, apixaban (SUCRA: 76.3) had the highest cumulative ranking probability, followed by edoxaban (SUCRA: 66.4), dalteparin (SUCRA: 28.8), and rivaroxaban (SUCRA: 28.5). Similar results were observed for clinically relevant bleeding. In terms of both benefit and safety outcomes, DOACs, especially edoxaban, seemed to confer a better NCB profile than dalteparin. Conclusions: DOACs are a safe and effective alternative therapy to dalteparin in patients with CAT. Among them, edoxaban might provide a good risk-to-benefit balance. However, because of the lack of head-to-head studies, further investigations are needed to confirm our findings.
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Background: Emerging evidence shows that coronavirus disease 2019 (COVID-19) is commonly complicated by coagulopathy, and venous thromboembolism (VTE) is considered to be a potential cause of unexplained death. Information on the incidence of VTE in COVID-19 patients, however, remains unclear. Method: English-language databases (PubMed, Embase, Cochrane), Chinese-language databases (CNKI, VIP, WANFANG), and preprint platforms were searched to identify studies with data of VTE occurrence in hospitalized COVID-19 patients. Pooled incidence and relative risks (RRs) of VTE were estimated by a random-effects model. Variations were examined based on clinical manifestations of VTE (pulmonary embolism-PE and deep vein thrombosis-DVT), disease severity (severe patients and non-severe patients), and rate of pharmacologic thromboprophylaxis (≥60 and <60%). Sensitivity analyses were conducted to strengthen the robustness of results. Meta-regression was performed to explore the risk factors associated with VTE in COVID-19 patients. Results: A total of 17 studies involving 1,913 hospitalized COVID-19 patients were included. The pooled incidence of VTE was 25% (95% CI, 19-31%; I 2, 95.7%), with a significant difference between the incidence of PE (19%; 95% CI, 13-25%; I 2, 93.2%) and DVT (7%; 95% CI, 4-10%; I 2, 88.3%; P interaction < 0.001). Higher incidence was observed in severe COVID-19 patients (35%; 95 CI%, 25-44%; I 2, 92.4%) than that in non-severe patients (6%; 95 CI%, 3-10%; I 2, 62.2%; P interaction < 0.001). The high rate of pharmacologic thromboprophylaxis in COVID-19 patients (≥60%) was associated with a lower incidence of VTE compared with the low pharmacologic thromboprophylaxis rate (<60%) (19 vs. 40%; P interaction = 0.052). Severe patients had a 3.76-fold increased risk of VTE compared with non-severe patients (RR, 4.76; 95% CI, 2.66-8.50; I 2, 47.0%). Sensitivity analyses confirmed the robustness of the primacy results. Conclusions: This meta-analysis revealed that the estimated VTE incidence was 25% in hospitalized COVID-19 patients. Higher incidence of VTE was observed in COVID-19 patients with a severe condition or with a low rate of pharmacologic thromboprophylaxis. Assessment of VTE risk is strongly recommended in COVID-19 patients, and effective measures of thromboprophylaxis should be taken in a timely manner for patients with high risk of VTE.
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Diabetes is a major cause of cardiovascular mortality in most countries. Intensive management of blood glucose is pivotal for alleviating disease progress and minimizing cardiovascular complications. In this study, we report a case of successful control of high blood glucose in a diabetes patient with acute coronary syndromes (ACS), hypertension, and renal insufficiency. This patient had five years of diabetes history and was hospitalized through an ACS emergency. Coronary angiography showed an acute anterior myocardial infarction (Killip Level I). The patient had extremely high blood glucose that ranged from 19.4 to 28.2 mmol/L on the first day in the hospital and experienced significant blood glucose fluctuations in the following three days. After two rounds of clinical pharmacist consultation, the patient's fasting blood glucose (FBG) target was achieved on the seventh day of his hospitalization and was well controlled afterward. The patient's postprandial blood glucose (PBG) target was achieved on the ninth day of hospitalization, and he was discharged when his blood glucose was well controlled and cardiac function had been fully assessed. Hence, we summarize a protocol that could be used to quickly adjust high blood glucose in hospitalized patients and report a new blood glucose management model coordinated by clinical pharmacists and clinicians.
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BACKGROUND: Current evidence regarding the effectiveness and safety of direct oral anticoagulants (DOACs) in the elderly with atrial fibrillation (AF) remains scarce. Based on the emerging evidence from real-world studies (RWSs) associated with DOACs, we will perform a systematic review and meta-analysis of data from RWSs and randomized controlled trials (RCTs) to compare the effectiveness, safety and cost of DOACs versus Vitamin K antagonists (VKAs) in elderly patients with AF. METHODS: The MEDLINE, EMBASE and Cochrane Library databases will be systematically searched until June 30, 2019 for eligible RWSs and RCTs that reported the clinical outcomes between DOACs and VKAs in elderly patients with AF. The effectiveness outcome is stroke or systemic embolism (SE), and the safety outcomes are major bleeding, intracranial haemorrhage (ICH), gastrointestinal bleeding (GIB), myocardial infarction (MI) and all-cause mortality. A random-effects model will be used to calculate adjusted hazard ratios (HRs) for RWSs and relative risks (RRs) for RCTs, separately. The interaction analysis and the ratio of HRs (RHRs) will be applied to compare the treatment effect difference between RWSs and RCTs. A Markov model will be constructed to evaluate the cost-effectiveness of DOACs versus VKAs in elderly AF patients in real-world setting. DISCUSSION: This study will summarize all available evidences from RWSs and RCTs for a comprehensive and rigorous systematic review on the effectiveness and safety associated with DOACs, as well as perform a cost-effectiveness analysis to evaluate the price performance of DOACs among elderly AF patients in real clinical setting. TRIAL REGISTRATION: PROSPERO register platform (CRD42019142881, www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID =142881).
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BACKGROUND & AIMS: There is controversy over whether use of non-vitamin K antagonist oral anticoagulants (NOACs) associates with increased risk of major gastrointestinal bleeding (GIB) compared with conventional therapies (such as vitamin K antagonists or anti-platelet agents). We performed a systematic review and meta-analysis of data from randomized controlled trials and high-quality real-world studies. METHODS: We performed a systematic search of the MEDLINE, EMBASE, Cochrane Library, and ClinicalTrials.gov Website databases (through Oct 12, 2018) for randomized controlled trials and high-quality real-world studies that reported major GIB events in patients given NOACs or conventional therapy. Relative risks (RRs) for randomized controlled trials and adjusted hazard ratios (aHRs) for real-world studies were calculated separately using random-effects models. RESULTS: We analyzed data from 43 randomized controlled trials (183,752 patients) and 41 real-world studies (1,879,428 patients). The pooled major rates of GIB for patients on NOACs (1.19%) vs conventional treatment (0.92%) did not differ significantly (RR from randomized controlled trials, 1.09; 95% CI, 0.91-1.31 and aHR from real-world studies, 1.02; 95% CI, 0.94-1.10; Pinteraction=.52). Rivaroxaban, but not other NOACs, was associated with an increased risk for major GIB (RR from randomized controlled trials, 1.39; 95% CI, 1.17-1.65 and aHR from real-world studies, 1.14; 95% CI, 1.04-1.23; Pinteraction = .06). Analyses of subgroups, such as patients with different indications, dosage, or follow-up time, did not significantly affect results. Meta-regression analysis failed to detect any potential confounding to impact the primacy outcome. CONCLUSIONS: In a systematic review and meta-analysis of data from randomized controlled trials and real-world studies, we confirmed that there is no significant difference in risk of major GIB between patients receiving NOACs vs conventional treatment. Rivaroxaban users had a 39% increase in risk for major GIB.
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Fibrilación Atrial , Accidente Cerebrovascular , Administración Oral , Anticoagulantes/efectos adversos , Fibrilación Atrial/tratamiento farmacológico , Fibrinolíticos/uso terapéutico , Hemorragia Gastrointestinal/inducido químicamente , Hemorragia Gastrointestinal/epidemiología , Humanos , Rivaroxabán/uso terapéuticoRESUMEN
BACKGROUND: Patients with warfarin have a potential risk of warfarin-related nephropathy, which could result in the discontinuation of anticoagulation therapy. The question of whether non-vitamin K antagonist oral anticoagulants (NOACs) use is associated with increased risk of renal impairment in atrial fibrillation (AF) patients remains unanswered. METHODS: Studies were systematically searched through Medline, Embase, Cochrane Library databases, and ClinicalTrials.gov Website. Randomized controlled trials (RCTs) reporting renal impairment events and observational nationwide database studies presenting adjusted hazard ratio (HR) in AF patients with NOACs were identified. The Primacy outcome was renal impairment, defined as a composite of any renal disorder. The secondary outcomes were narrow definition of renal failure (including renal failure, acute renal failure, chronic renal failure, acute prerenal failure and postrenal failure) and individual renal impairment reported in involved studies. HR and 95% confidence intervals (95%CI) were calculated using fixed- or random-effects models according to the extent of heterogeneity. Subgroup analyses were conducted according to individual NOACs, study types and different controls. RESULTS: Totally, 189,483 patients from 11 RCTs and 3 observational database studies were included in the analysis (119,188 patients with NOACs and 70,295 patients with vitamin K Antagonists or acetylsalicylic acid). Overall results indicated a significantly lower risk of renal impairment in AF patients with NOACs versus VKAs/acetylsalicylic acid (HR: 0.67, 95%CI: 0.62-0.73). Results of narrow definition of renal impairment were accordant with the primacy outcome (HR: 0.65, 95%CI: 0.60-0.71). Compared with VKAs or acetylsalicylic acid, dabigatran (HR: 0.64, 95%CI: 0.56-0.72), rivaroxaban (HR: 0.66, 95%CI: 0.55-0.77) and apixaban (HR: 0.73, 95%CI: 0.59-0.87) were all associated with a significantly lower risk of renal impairment, with the exception of edoxaban (HR: 0.79, 95%CI: 0.30-1.27). CONCLUSIONS: Patients with NOACs might bring about a lower risk of renal impairment compared to VKA or acetylsalicylic acid. Further specialized designs of RCTs and real-world studies on evaluation of renal function are warranted to obtain a robust result on this issue.
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Anticoagulantes/uso terapéutico , Fibrilación Atrial/tratamiento farmacológico , Insuficiencia Renal/etiología , Warfarina/uso terapéutico , Administración Oral , Fibrilación Atrial/patología , Femenino , Humanos , Masculino , Ensayos Clínicos Controlados Aleatorios como Asunto , Insuficiencia Renal/patología , Warfarina/farmacologíaRESUMEN
Background: The relationship between the use of non-vitamin K antagonist oral anticoagulants (NOACs) and the impairment of cognition in atrial fibrillation (AF) remains unknown. Methods: A comprehensive database search of Medline, Embase, Cochrane Library databases, and ClinicalTrials.gov Website was performed for randomized controlled trials (RCTs) reporting cognitive impairment events and observational nationwide database studies reporting adjusted hazard ratio (HR) in AF patients with NOACs. The primacy outcome was a composite of any cognitive impairment. Summary of HRs and 95% confidence intervals (95%CI) were calculated using the fixed- and random-effects models. Subgroup analyses were undertaken according to the individual NOACs, study types, and duration of follow-up. Results: Finally, eight studies including 97,595 patients (77,643 patients in 6 RCTs and 19,952 patients in 2 observational database studies) met the inclusion criteria, among which 55,337 (56.7%) patients were receiving NOACs and 42,258 (43.3%) patients were receiving vitamin K Antagonists (VKAs) or acetylsalicylic acid. The results showed a borderline significant association between the use of NOACs and the lower risk of cognitive impairment when compared with VKAs/ acetylsalicylic acid (HR: 0.80, 95%CI: 0.63-0.98 for fixed-effects model; HR: 0.77; 95%CI: 0.53-1.01 for random-effects model), with no significant heterogeneity between the studies (I 2 = 39.4%, P = 0.12). The results were consistent across the key subgroups (P interaction > 0.05 for each). Conclusions: The results indicated that the use of NOACs might lower the tendency on the risk of cognitive impairment in comparison to VKAs/acetylsalicylic acid, and further RCTs and real-world studies are required on an urgent basis to obtain a robust result.
RESUMEN
BACKGROUND: The relationship of CYP2C19 genotype and clinical efficacy in stroke or transient ischemic attack (TIA) patients treated with clopidogrel monotherapy or clopidogrel plus aspirin remains unknown. We thus aim to conduct a meta-analysis to appraise evidence on the association of CYP2C19 genotype and clinical efficacy for stroke or TIA. METHODS: An electronic search will be performed for clinical trials that reported the interested efficacy data (stroke, myocardial infarction, or vascular death) and safety data (any bleeding) in clopigogrel-treated patients with stroke or TIA. Odds ratios (ORs) with their confidence intervals (CIs) will be calculated using a meta-analysis. RESULTS: This study will provide the evidence of the relationship between CYP2C19 genotype and clinical efficacy and safety in stroke/TIA patients taking clopidogrel by pooling the results of individual studies. CONCLUSIONS: The results will bring about vigorous evidence in this issue and guide both clinical decision-making and future research.
Asunto(s)
Aspirina , Citocromo P-450 CYP2C19 , Ataque Isquémico Transitorio , Inhibidores de Agregación Plaquetaria , Accidente Cerebrovascular , Ticlopidina , Humanos , Aspirina/efectos adversos , Aspirina/uso terapéutico , Clopidogrel , Citocromo P-450 CYP2C19/genética , Quimioterapia Combinada , Genotipo , Ataque Isquémico Transitorio/tratamiento farmacológico , Ataque Isquémico Transitorio/genética , Inhibidores de Agregación Plaquetaria/efectos adversos , Inhibidores de Agregación Plaquetaria/uso terapéutico , Accidente Cerebrovascular/tratamiento farmacológico , Accidente Cerebrovascular/genética , Ticlopidina/efectos adversos , Ticlopidina/análogos & derivados , Ticlopidina/uso terapéutico , Resultado del Tratamiento , Metaanálisis como Asunto , Revisiones Sistemáticas como AsuntoRESUMEN
BACKGROUND: Pulmonary arterial hypertension (PAH) is a progressive disease and ultimately leads to right heart failure. Endothelin receptor antagonists (ERAs) have been demonstrated to significantly improve prognosis in PAH. However, ERAs-induced side effects can result in poor patient tolerance. Thus, we aim to evaluate current safety evidence of ERAs in PAH. METHODS: An electronic search will be performed for randomized controlled trials (RCTs) that reported the interested safety data (abnormal liver function, peripheral edema, and anemia) of ERAs in PAH. Risk ratios (RRs) with their confidence intervals (CIs) and the surface under the cumulative ranking curve (SUCRA) will be calculated using a network analysis. RESULTS: This study will provide the safety evidence of ERAs in PAH by combining the results of individual studies based on direct- and network comparison, and to rank ERAs in the evidence network. CONCLUSIONS: The results will supplement missing evidence of head-to-head comparisons between different ERAs and guide both clinical decision-making and future research.