Publications by authors named "Zhi-Chun Gu"

59 Publications

An Adapted Neural-Fuzzy Inference System Model Using Preprocessed Balance Data to Improve the Predictive Accuracy of Warfarin Maintenance Dosing in Patients After Heart Valve Replacement.

Cardiovasc Drugs Ther 2021 Apr 20. Epub 2021 Apr 20.

Department of Evidence-Based Medicine and Clinical epidemiology, West China Hospital, Sichuan University, Chengdu, China.

Background: Tailoring warfarin use poses a challenge for physicians and pharmacists due to its narrow therapeutic window and substantial inter-individual variability. This study aimed to create an adapted neural-fuzzy inference system (ANFIS) model using preprocessed balance data to improve the predictive accuracy of warfarin maintenance dosing in Chinese patients undergoing heart valve replacement (HVR).

Methods: This retrospective study enrolled patients who underwent HVR between June 1, 2012, and June 1, 2016, from 35 centers in China. The primary outcomes were the mean difference between predicted warfarin dose by ANFIS models and actual dose and the models' predictive accuracy, including the ideal predicted percentage, the mean absolute error (MAE), and the mean squared error (MSE). The eligible cases were divided into training, internal validation, and external validation groups. We explored input variables by univariate analysis of a general linear model and created two ANFIS models using imbalanced and balanced training sets. We finally compared the primary outcomes between the imbalanced and balanced ANFIS models in both internal and external validation sets. Stratified analyses were conducted across warfarin doses (low, medium, and high doses).

Results: A total of 15,108 patients were included and grouped as follows: 12,086 in the imbalanced training set; 2820 in the balanced training set; 1511 in the internal validation set; and 1511 in the external validation set. Eight variables were explored as predictors related to warfarin maintenance doses, and imbalanced and balanced ANFIS models with multi-fuzzy rules were developed. The results showed a low mean difference between predicted and actual doses (< 0.3 mg/d for each model) and an accurate prediction property in both the imbalanced model (ideal prediction percentage, 74.39-78.16%; MAE, 0.37 mg/daily; MSE, 0.39 mg/daily) and the balanced model (ideal prediction percentage, 73.46-75.31%; MAE, 0.42 mg/daily; MSE, 0.43 mg/daily). Compared to the imbalanced model, the balanced model had a significantly higher prediction accuracy in the low-dose (14.46% vs. 3.01%; P < 0.001) and the high-dose warfarin groups (34.71% vs. 23.14%; P = 0.047). The results from the external validation cohort confirmed this finding.

Conclusions: The ANFIS model can accurately predict the warfarin maintenance dose in patients after HVR. Through data preprocessing, the balanced model contributed to improved prediction ability in the low- and high-dose warfarin groups.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10557-021-07191-1DOI Listing
April 2021

Effectiveness and Safety of Under or Over-dosing of Direct Oral Anticoagulants in Atrial Fibrillation: A Systematic Review and Meta-analysis of 148909 Patients From 10 Real-World Studies.

Front Pharmacol 2021 18;12:645479. Epub 2021 Mar 18.

School of Medicine, Tongji University, Shanghai, China.

In routine clinical practice, non-standard doses of direct oral anticoagulants (DOACs) are commonly used in patients with atrial fibrillation (AF). However, data on the clinical outcomes of non-standard doses of DOACs are limited. The MEDLINE, Embase, and Cochrane Library databases were systematically searched from their inception until 30 June 2020 for studies that reported the effectiveness or safety outcomes of non-standard doses of DOACs compared with on-label doses of DOACs in patients with atrial fibrillation. Non-standard doses of DOACs were defined as under or over-dose of DOACs based on the recommended standard doses in drug labels. A random-effects meta-analysis was performed to calculate the pooled hazard ratio and associated 95% confidence interval (95% confidence interval). Subgroup analyses were conducted according to individual DOACs and different geographic regions. Ten articles involving 148,909 patients with AF were included. There were no significant differences between under-dosing and on-label dosing with respect to stroke/systematic embolism (HR: 1.01, 95% CI: 0.93-1.09), major bleeding (HR: 0.98, 95% CI: 0.77-1.19), intracranial haemorrhage (HR: 1.07, 95% CI: 0.74-1.40), gastrointestinal bleeding (HR: 1.10, 95% CI: 0.82-1.39), and myocardial infarction (HR: 1.07, 95% CI: 0.89-1.25), except for an increased risk of death (HR: 1.37, 95% CI: 1.01-1.73). We observed a significant association between over-dosing of DOACs and increased risk of stroke/systematic embolism (HR: 1.18, 95% CI: 1.04-1.32), major bleeding (HR: 1.16, 95% CI: 1.03-1.29), and death (HR: 1.21, 95% CI: 1.03-1.38) compared with on-label dosing. Furthermore, over-dosing of DOACs increased the risk of stroke/systematic embolism (HR: 1.16; 95% CI: 1.00-1.33) and major bleeding events (HR: 1.18; 95% CI: 1.00-1.37) in Asian patients. A reduced dose of DOACs might be safely and effectively used in clinical practice, especially in Asian patients, whereas high-dose DOACs might not be well tolerated by Asian patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fphar.2021.645479DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8012667PMC
March 2021

Incidence and Risk of Infection Associated With Fingolimod in Patients With Multiple Sclerosis: A Systematic Review and Meta-Analysis of 8,448 Patients From 12 Randomized Controlled Trials.

Front Immunol 2021 8;12:611711. Epub 2021 Mar 8.

Department of Pharmacy, Huashan Hospital, Fudan University, Shanghai, China.

There is a controversy regarding whether fingolimod is associated with an increased risk of infection in patients with multiple sclerosis (MS). We performed a systematic review and meta-analysis of data from randomized controlled trials (RCTs) to determine the risk of infection in these patients. We systematically searched PubMed, EMBASE, the Cochrane Library, and clinicaltrials.gov from inception to April 8, 2020, to identify RCTs that reported the occurrence of infection in patients with MS treated with fingolimod. Relative risks (RRs) and 95% confidence intervals (95% CIs) were calculated using the random-effects model. Twelve RCTs including 8,448 patients were eligible. Compared with the control (placebo and other active treatments), fingolimod significantly increased the risk of infection (RR, 1.16; 95% CI, 1.07-1.27; , 81%), regardless of whether the infection was a general infection (RR, 1.14; 95% CI, 1.05-1.25; , 78%), or a serious infection (RR, 1.49; 95% CI, 1.06-2.10; , 0%). Analyses of subgroups found that fingolimod significantly increased the risk of lower respiratory infection (RR, 1.48; 95% CI, 1.19-1.85; , 0%) and herpes virus infection (RR, 1.34; 95% CI, 1.01-1.78; , 9%). There appears to be no dose-dependent increase in the risk of infection associated with fingolimod (0.5 mg: RR, 1.15; 95% CI, 1.07-1.25; , 91%; 1.25 mg: RR, 1.11; 95% CI, 0.97-1.28; , 81%; P = 0.66). Compared with a placebo and other active treatments, fingolimod was associated with a 16% increase in the risk of infection, especially lower respiratory infection and herpes virus infection. The risk of infection associated with fingolimod might not be dose related.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fimmu.2021.611711DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7982402PMC
March 2021

Intervention by clinical pharmacists can improve blood glucose fluctuation in patients with diabetes and acute myocardial infarction: A propensity score-matched analysis.

Pharmacol Res Perspect 2021 Apr;9(2):e00725

Department of Pharmacy, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.

Acute phase hyperglycemia and exaggerated glucose fluctuation may be associated with poor outcomes in diabetic patients after acute myocardial infarction (AMI). This study aimed to determine whether intervention by clinical pharmacists can mitigate blood glucose and glucose fluctuations in these fragile patients. This retrospective study enrolled patients with diabetes and AMI, from 1 January 2019 to 30 June 2020 in our institution. Blood glucose and glucose fluctuations were calculated before and after the pharmacist's intervention and between patients who underwent intervention and those who did not. Propensity score matching (PSM) was used to reduce the impact of patient characteristics on the results. A total of 170 patients were included in our primary analysis, including 29 patients who received the pharmacist intervention and 141 patients who did not. After the pharmacist's intervention, blood glucose (fasting blood glucose-FBG, from 11.9 to 9.8; postprandial blood glucose-PBG, from 15.3 to 13.2; mean blood glucose-BG, 14.5 to 12.3 mmol/L; p < .001), and glucose fluctuations (standard deviation of blood glucose-SDBG, from 3.8 to 3.0, mmol/L, p = .005) were significantly improved. Before PSM, no clear effects were found in intervention versus nonintervention patients, in terms of blood glucose and glucose fluctuation indicators, except for FBG (9.3 vs. 8.0. mmol/L, p = .005). Further analysis indicated a high incidence of FBG <7.8 mmol/L in nonintervention versus intervention patients (51.5% vs. 27.6%, p = .003). After PSM, a significant reduction in blood glucose fluctuation (SDBG, 3.0 vs. 4.1, p = .031; PBGE, 2.1 vs. 4.1, p = .017; LAGE, 4.7 vs. 7.2, mmol/L, p = .004), and PBG (11.1 vs. 13.0, mmol/L, p = .048) was observed in the intervention group than in the nonintervention group. The clinical pharmacist intervention contributed to improved outcomes, specifically, in reducing blood glucose fluctuations and potential hypoglycemia risk.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/prp2.725DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7914773PMC
April 2021

Efficacy and safety of tigecycline for complicated urinary tract infection: a systematic review.

Transl Androl Urol 2021 Jan;10(1):292-299

Department of Pharmacy, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.

Background: Facing the global threat of emerging resistance to antibiotics, tigecycline, a novel glycylcycline antibiotic, is developed to against multidrug-resistant pathogens, but not recommended for the treatment of complicated urinary tract infection (cUTI). We performed a summary of the literatures to characterize and evaluate the efficacy and safety of tigecycline in patients with cUTI.

Methods: We searched PubMed, EMBASE, Cochrane and Clinical Trials using appropriate syntax to retrieve potential articles up to Jan 2020. General information, pathogen, medication regimen, comorbidities of patients from eligible literatures were recorded. Univariate logistic regression analysis was used to detect the potential factors associated with clinical cure.

Results: Nineteen articles comprising 31 cases were included. The subpopulation with transplantation (25.8% of the patients) was the most common comorbidity, and cUTIs were mainly caused by () (48.28%) in our research. Tigecycline 100 mg per day as monotherapy was most common. Clinical cure was reported as majority (77.4%), and microbiological eradication cases accounted for the most (65.2%) among the clinical cure cases. Univariate analysis showed that caused cUTI and tigecycline as a single treatment have significant meaning to clinical outcomes (P=0.044 and P=0.034, respectively).

Conclusions: Clinical and microbiological outcomes of tigecycline treatment revealed high rate of successful response. Tigecycline monotherapy may have a role in the treatment of cUTI except that caused by the pathogen . Further randomized controlled trials was still needed to evaluate tigecycline monotherapy for cUTI.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21037/tau-20-959DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7844507PMC
January 2021

Anticoagulation Quality of Warfarin and the Role of Physician-Pharmacist Collaborative Clinics in the Treatment of Patients Receiving Warfarin: A Retrospective, Observational, Single-Center Study.

Front Pharmacol 2020 14;11:605353. Epub 2021 Jan 14.

Department of Pharmacy, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.

The management of patients receiving warfarin is complicated. This study evaluated the anticoagulation quality of warfarin, explored potential predictors associated with poor anticoagulation quality, and elucidated the role of clinical pharmacists in the management of warfarin treatment. We retrospectively collected data on patients who either initially received warfarin or returned to warfarin after withdrawal between January 1, 2015 and January 1, 2020. The primary outcome was time in therapeutic range (TTR), and a TTR of ≥60% was considered as good anticoagulation quality. The secondary outcomes included thromboembolic and bleeding events during the follow-up. We assessed the TTR of each participant and investigated the potential predictors of poor anticoagulation quality (TTR < 60%) using logistic regression analysis. Additionally, we compared the warfarin anticoagulant quality and the incidence of clinical adverse events between atrial fibrillation patients in physician-pharmacist collaborative clinics (PPCCs) and general clinics. Totally, 378 patients were included. The mean TTR of patients was 42.6 ± 29.8%, with only 32% of patients having achieved good anticoagulation quality. During a mean follow-up period of 192 ± 92 days, we found no significant differences in the incidences of thromboembolic events (5.0% vs. 5.1%, = 0.967) and bleeding events (1.7% vs. 4.7%, = 0.241) between patients with good and those with poor anticoagulation quality. The presence of PPCCs (odds ratio [OR]: 0.47, 95% confidence interval [CI]: 0.25-0.90, = 0.022) was an independent protective factor of poor anticoagulation quality, while the presence of more than four comorbidities (OR: 1.98, 95% CI: 1.22-3.24, = 0.006) and an average interval of international normalized ratio monitoring of >30 days (OR: 1.74, 95% CI: 1.10-2.76, = 0.019) were independent risk factors of poor anticoagulation quality. Compared with atrial fibrillation patients in general clinics, patients in PPCCs were found to have a significantly increased mean TTR level (48.4% ± 25.7% vs. 38.0% ± 27.6%, = 0.014). The anticoagulation quality of warfarin was relatively low at our institution. The presence of more than four comorbidities and an average interval of international normalized ratio monitoring of >30 days independently contributed to poor anticoagulation quality. Meanwhile, the use of PPCC model improved the anticoagulation quality of warfarin.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fphar.2020.605353DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7840488PMC
January 2021

Platelet-fibrin clot strength measured by thromboelastography could predict hypercoagulability and antiplatelet effects in patients after percutaneous coronary intervention.

Ann Palliat Med 2021 Mar 4;10(3):2448-2457. Epub 2021 Jan 4.

School of Pharmacy, Nantong University, Nantong, China.

Background: It has been estimated that nearly one-fifth post-percutaneous coronary intervention (PCI) patients treated with clopidogrel continued to have recurrent thrombotic events, which implied the limitation of "one-size-fits all" strategy for antiplatelet therapy.

Methods: From July 2017 to April 2019, patients with acute coronary syndrome [ACS, including unstable angina (UA), non-ST segment elevation myocardial infraction (NSTEMI), and ST segment elevation myocardial infraction (STEMI)] or old myocardial infarction (OMI), or patients without coronary heart disease (non-CAD) were retrospectively enrolled in this study. For CAD patients undergoing PCI, standard dual antiplatelet therapy (100 mg aspirin and 75 mg clopidogrel) was prescribed. After administration of dual antiplatelet agents for at least 5 days, whole blood samples were collected and platelet function was tested using thrombelastography (TEG). Thrombin-induced platelet-fibrin clot strength (MAthrombin) and ADPinduced platelet-fibrin clot strength (MAADP) were measured to assess the hypercoagulability and antiplatelet effects.

Results: A total of 571 patients, including 479 ACS patients, 21 OMI patients and 71 non-CAD patients were enrolled. Highest level of MAthrombin was detected in STEMI patients, while lowest MAthrombin level was observed in non-CAD patients (P1 <0.05 for OMI vs. non-CAD; P2 <0.001 for ACS vs. non-CAD; P3<0.05 among ACS). Higher MAADP was also observed in STEMI and NSTEMI patients compared with UA patients (P<0.001). When MAADP was divided into trisections (MAADP <31; 31-47; >47 mm), a considerable portion of 41.8% ACS patients were in the first trisection (MAADP <31 mm), containing 50.4% of UA patients, 35.7% of NSTEMI patients and 26.5% of STEMI patients, with significant difference being observed between UA patients and other ACS patients (P<0.05 for NSTEMI vs. UA; P<0.001 for STEMI vs. UA). Meanwhile, 27.6% of NSTEMI and 31.0% of STEMI patients were in the third trisection (MAADP >47 mm), which was significantly higher than that of UA patients (12.7%) (P<0.001 for NSTEMI or STEMI vs. UA).

Conclusions: Considering various degrees of hypercoagulability and antiplatelet effects of clopidogrel among OMI and ACS patients post-PCI. More attention should be paid to personalized antiplatelet therapy according to individual's effects of P2Y12 receptor inhibitors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21037/apm-20-1728DOI Listing
March 2021

Drug-related problems among hospitalized cancer pain patients: an investigative single-arm intervention trial.

Ann Palliat Med 2021 Feb 22;10(2):2008-2017. Epub 2020 Dec 22.

Department of Pharmacy, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Background: To evaluate the characteristics of drug-related problems (DRPs) in cancer pain patients, and to identify the impact of pharmacists' intervention in cancer pain associated DRPs.

Methods: In this investigative, single-arm intervention study, clinical pharmacists identified DRPs in cancer pain patients and provided interventions based on medication information, direct patient-pharmacist interview, and ward rounds with multi-disciplinary team (MDT). Types and causes of DRPs, interventions, acceptance and outcome were sorted based on Pharmaceutical Care Network Europe (PCNE) DRP classification V9.0, which includes 3 primary domains for problems, 9 for causes, 5 for interventions, 3 for acceptance, and 4 for DRPs status.

Results: Totally, 42 cancer pain patients were enrolled, and 47 DRPs in 33 (78.6%) patients were identified by clinical pharmacists. The major type of DRPs was treatment effectiveness (30; 63.8%) and treatment safety (17; 36.2%). For the "treatment effectiveness" category, the "effect of drug treatment not optimal" was dominant category (27/30; 90%). A total of 66 DRP causes were identified, and most of DRPs were caused by "drug selection" (27; 40.9%) and "dose selection" (16; 24.2%). Within the "drug selection" category, "no or incomplete drug treatment in spite of existing indication" was dominant category (25/27; 92.6%). According to DRPs, 159 interventions were provided by clinical pharmacists and 99.4% of interventions were accepted by prescribers or patients. Finally, 44 (93.6%) DRPs were solved.

Conclusions: In cancer pain patients, insufficient pain control mainly caused by inappropriate selection and dosage of analgesics. Clinical pharmacists' interventions dramatically ameliorate these problems and bring about positive effects in cancer pain pharmacotherapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21037/apm-20-1458DOI Listing
February 2021

Current therapeutic options for coronavirus disease 2019 (COVID-19)-lessons learned from severe acute respiratory syndrome (SARS) and Middle East Respiratory Syndrome (MERS) therapy: a systematic review protocol.

Ann Transl Med 2020 Nov;8(22):1527

Department of Pharmacy, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Background: Coronavirus disease 2019 (COVID-19), also known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, first manifested in December 2019, and spread rapidly worldwide. Facing this lethal disease, there is an urgent need to develop potent therapies against SARS-CoV-2 infection. SARS-CoV-2 phylogenetically and symptomatically resembles SARS-CoV and Middle East Respiratory Syndrome Coronavirus (MERS-CoV). Numerous agents have been utilised during the severe acute respiratory syndrome (SARS) and Middle East Respiratory Syndrome (MERS) epidemics, which may show some benefit against SARS-CoV-2.

Methods: MEDLINE, EMBASE, Cochrane Library, CBM Disc, China National Knowledge Infrastructure, Wanfang Data, and the China Science and Technology Journal Database will be searched. Manual searches will be conducted by searching pre-printing websites, clinical trial registers, and screening the reference lists of inclusive studies. The screening of all citations and the selection of inclusive articles will be conducted by two reviewers. Randomised controlled trials (RCTs) and controlled cohort studies reporting antiviral therapies, including ribavirin, remdesivir, lopinavir/ritonavir, arbidol, chloroquine, hydroxychloroquine, and interferon, for SARS, MERS, and COVID-19 will be included. The primary outcomes will be mortality, incidence of acute respiratory distress syndrome, and utilisation of mechanical ventilation and intensive care unit admission. The secondary outcomes will be improvement in symptoms and chest radiography results, virus clearance, changes in blood test results, and serum tests. The quality of the retrieved RCTs and observational studies will be appraised according to the Cochrane risk of bias tool and the Newcastle-Ottawa Scale, respectively. If feasible, we will perform a fixed- or random-effects meta-analysis.

Discussion: This systematic review and meta-analysis will summarise all the available evidence for the efficacy and safety of current therapeutic options in SARS-CoV, MERS-CoV, or SARS-CoV-2-infected patients. The findings of this study may inform subsequent antiviral interventions for patients with COVID-19.

Study Registration: The protocol of this study has been submitted to the PROSPERO platform (https://www.crd.york.ac.uk/PROSPERO/), and the registration number is CRD42020168639.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21037/atm-20-2340DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7729372PMC
November 2020

Net Clinical Benefit of Direct Oral Anticoagulants in Patients With Cancer and Venous Thromboembolism: A Systematic Review and Trade-Off Analysis.

Front Cardiovasc Med 2020 12;7:586020. Epub 2020 Nov 12.

Department of Pharmacy, School of Medicine, Renji Hospital, Shanghai Jiaotong University, Shanghai, China.

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. 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. 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. 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fcvm.2020.586020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7693545PMC
November 2020

Direct Oral Anticoagulants vs. Vitamin-K Antagonists in the Elderly With Atrial Fibrillation: A Systematic Review Comparing Benefits and Harms Between Observational Studies and Randomized Controlled Trials.

Front Cardiovasc Med 2020 10;7:132. Epub 2020 Sep 10.

Department of Evidence-Based Medicine and Clinical Epidemiology, West China Hospital, Sichuan University, Chengdu, China.

The publication of high-quality observational studies (OSs) has fueled reassessment of the treatment effects of direct oral anticoagulants (DOACs) in the elderly with atrial fibrillation (AF). The MEDLINE, EMBASE, and Cochrane Library databases were systematically searched (through July 1, 2019) for eligible OSs and randomized controlled trials (RCTs) that reported effectiveness outcomes [stroke or systemic embolism (SE)] or safety outcomes [intracranial hemorrhage (ICH), major bleeding, gastrointestinal bleeding (GIB), myocardial infarction (MI), and all-cause mortality] for DOACs and vitamin-K antagonists (VKAs) in elderly AF patients. A random-effects model was applied to calculate adjusted hazard ratios (HRs) for OSs and relative risks (RRs) for RCTs. Interaction analyses and the ratio of HR (RHR) were used to assess and compare OSs and RCTs. A total of 32 studies involving 547,419 patients were included. No significant difference in treatment effect estimates was found between 27 OSs and 5 RCTs [ > 0.05 for each and all 95% confidence interval (CI) of RHR crossed 1.0]. Compared with VKAs, DOACs significantly reduced risk for stroke/SE (OSs, HR: 0.87, 95% CI: 0.81-0.94; RCT, RR: 0.82, 95% CI: 0.67-0.96), and ICH (OSs: 0.47 [0.37-0.57]; RCTs: 0.47 [0.31-0.63]), without increasing risk for GIB (OSs: 1.21 [0.98-1.43]; RCTs: 1.34 [0.91-1.77]), and all-cause mortality (OSs: 1.01 [0.92-1.11]; RCTs: 0.94 [0.87-1.00]). Among OSs, DOACs significantly decreased risk for major bleeding (0.87 [0.77-0.98]) and MI (0.89 [0.79-0.99]). It was found that dabigatran, but not other DOACs, significantly increased risk for GIB (1.48 [1.23-1.72]). DOACs were demonstrated to be more effective and safer than VKAs in elderly AF patients, whereas dabigatran users had a 48% increase in risk for GIB.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fcvm.2020.00132DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7511536PMC
September 2020

Management of Bivalirudin Anticoagulation Therapy for Extracorporeal Membrane Oxygenation in Heparin-Induced Thrombocytopenia: A Case Report and a Systematic Review.

Front Pharmacol 2020 11;11:565013. Epub 2020 Sep 11.

Department of Critical Care, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.

Extracorporeal membrane oxygenation (ECMO) can provide respiratory and cardiac support to patients in reversible devastated conditions. Heparin is the mainstay for anticoagulation during ECMO. Bivalirudin, a direct thrombin blocker, may represent an effective alternative for patients suffering from heparin-induced thrombocytopenia (HIT). We present the first case of a Chinese patient who experienced HIT and received bivalirudin anticoagulation during ECMO. In addition, we present a systematic review for this topic. We searched PubMed, EMBASE, and Cochrane Library (up to April 20, 2020) for studies that included patients undergoing ECMO, presenting with HIT, requiring bivalirudin treatment, and reporting relevant outcomes. The literature review yielded 15 studies involving 123 patients, amongst whom 58 patients were confirmed or suspected HIT patients, and 76 patients received bivalirudin as an anticoagulant for ECMO. Twelve studies were included for quantitative synthesis, and 46 patients were retrieved. The mean age of these patients was 46 years, and 30 patients were males. The average maintenance rate of bivalirudin was 0.27 ± 0.37 mg/kg/h, in order to maintain a target of activated clotting time (ACT) of 160-220 s. Additionally, bivalirudin doses in patients with continuous renal replacement therapies (CRRT) and patients without CRRT were 0.15 ± 0.06 mg/kg/h vs 0.28 ± 0.36 mg/kg/h, respectively (=0.15). Most of the patients with confirmed HIT improved platelet counts in 3.3 ± 2.8 days after switching to bivalirudin anticoagulation. The patient-level data showed that 29 cases survived, 1 reported major bleeding, and 4 reported thrombotic events. Bivalirudin might be a promising optimal choice for ECMO anticoagulation in patients with HIT. A tailored protocol for management of bivalirudin treatment during ECMO should be developed with caution. Further prospective studies are necessary to standardise the use of bivalirudin.

Systematic Review Registration: PROSPERO, identifier CRD42020160907.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fphar.2020.565013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7516194PMC
September 2020

Incidence of myocardial injury in coronavirus disease 2019 (COVID-19): a pooled analysis of 7,679 patients from 53 studies.

Cardiovasc Diagn Ther 2020 Aug;10(4):667-677

Department of Pharmacy, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Background: Coronavirus disease 2019 (COVID-19) has become global pandemic and resulted in considerable morbidity and mortality since December 2019. Information on the incidence of myocardial injury remains scarce.

Methods: English-language databases (PubMed, Embase, Cochrane), Chinese-language databases (CNKI, VIP, WANFANG), and preprint platform were searched to identify studies that reported the myocardial injury data in COVID-19 patients. Random-effects meta-analyses were used to derive the pooled incidence and relative risks (RRs) of myocardial injury. Variations by disease severity were examined by subgroup analyses. Sensitivity analyses were performed to strengthen the results. Meta-regression was applied to explore the risk factors associated with myocardial injury.

Results: A total of 53 studies involving 7,679 patients were included. The pooled incidence of myocardial injury was 21% [95% confidence interval (CI), 17-25%; I, 96.5%]. The highest incidence of myocardial injury was found in non-survivors (66%; 95 CI%, 54-78%; I, 85.7%), followed by severe patients (43%; 95 CI%, 33-53%; I, 93.0%) and non-severe patients (11%; 95 CI%, 7-15%; I, 95.2%). Higher risk of myocardial injury was detected in severe patients than non-severe patients (RR, 5.74; 95% CI, 3.74-8.79; I, 86.8%). All the sensitivity analyses confirmed the robustness of primacy results.

Conclusions: This meta-analysis showed that myocardial injury occurred in 21% of COVID-19 patients. An elevated rate was observed in non-survivors (66%) and severe patients (43%). Severe patients had a 4.74-fold increase in the risk of myocardial injury than non-severe patients. Aggressive strategy may be considered for COVID-19 patients at high risk of myocardial injury.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21037/cdt-20-535DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7487385PMC
August 2020

Incidence of Venous Thromboembolism in Hospitalized Coronavirus Disease 2019 Patients: A Systematic Review and Meta-Analysis.

Front Cardiovasc Med 2020 6;7:151. Epub 2020 Aug 6.

Department of Pharmacy, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.

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. 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. 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%; , 95.7%), with a significant difference between the incidence of PE (19%; 95% CI, 13-25%; , 93.2%) and DVT (7%; 95% CI, 4-10%, 88.3%; < 0.001). Higher incidence was observed in severe COVID-19 patients (35%; 95 CI%, 25-44%; , 92.4%) than that in non-severe patients (6%; 95 CI%, 3-10%; , 62.2%; < 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%; = 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; , 47.0%). Sensitivity analyses confirmed the robustness of the primacy results. 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fcvm.2020.00151DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7423832PMC
August 2020

Clinical Adverse Events of High-Dose vs Low-Dose Sodium-Glucose Cotransporter 2 Inhibitors in Type 2 Diabetes: A Meta-Analysis of 51 Randomized Clinical Trials.

J Clin Endocrinol Metab 2020 11;105(11)

Department of Pharmacy, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.

Aims: The aims of this work are to assess the clinical adverse events (AEs) of high-dose vs low-dose sodium-glucose cotransporter 2 inhibitors (SGLT2 inhibitors) in patients with type 2 diabetes mellitus (T2DM).

Methods: We searched MEDLINE, EMBASE, and Cochrane Library from January 1, 2006 to March 10, 2020, for identifying eligible randomized clinical trials (RCTs) that reported AEs by high-dose and low-dose SGLT2 inhibitors in T2DM patients. Random-effects models was used to obtain summary relative risks (RRs) with associated 95% CIs. Prespecified subgroup analyses according to individual SGLT2 inhibitors and follow-up duration, and leave-one-out sensitivity analysis were conducted.

Results: A total of 51 RCTs involving 24 371 patients (12 208 received high-dose and 12 163 received low-dose SGLT2 inhibitors) were included. Overall, the heterogeneity among included studies was relatively low (I2 < 50% for each outcome). No significant differences between high-dose and low-dose SGLT2 inhibitors were observed for overall safety (including any AEs, serious AEs, AEs leading to discontinuation, and death) and specified safety (including infections and infestations, musculoskeletal disorders, gastrointestinal disorders, osmotic diuresis-related AEs, volume-related AEs, renal-related AEs, and metabolism and nutrition), except for a mild increase in risk for AEs related to study drugs (RR: 1.08; 95% CI, 1.01-1.16) that mainly derived from canagliflozin (RR: 1.17; 95% CI, 1.05-1.30). Subgroup analyses were consistent with the primary outcomes.

Conclusions: This study provided substantial evidence that AEs of SGLT2 inhibitors were not dose related.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1210/clinem/dgaa586DOI Listing
November 2020

Successful thrombolytic therapy in acute ischemic stroke after reversal of warfarin: a case report.

Ann Palliat Med 2020 Aug 7. Epub 2020 Aug 7.

Department of Pharmacy, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.

It is essential for acute ischemic stroke (AIS) patients to receive timely revascularization. However, intravenous thrombolysis (IVT) is not recommended for AIS patients with warfarin associated hypocoagulability. Meanwhile, monotherapy of coagulation factors or vitamin K is unable to reverse anticoagulation of warfarin in emergency. Thus, developing an effective IVT strategy poses a challenging task for these fragile population. Herein, an 82-year-old male, on regular administration with warfarin because of nonvalvular atrial fibrillation (NVAF), suffered from AIS and had an elevated international normalized ratio value of 1.72 and prolonged prothrombin time of 18.2 s at stroke onset. For normalizing INR, combination of 4 factor prothrombin complex concentrate, fresh frozen plasma and vitamin K1 were administrated. Finally, the patient successfully received recombinant tissue plasminogen activator (rt-PA), with an obviously neurological improvement. This case shows a feasible role of IVT therapy with rt-PA after reversal of coagulation regarding AIS patients with warfarin-related hypocoagulability.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21037/apm-20-868DOI Listing
August 2020

Preliminary exploration on the role of clinical pharmacists in cancer pain pharmacotherapy.

Ann Palliat Med 2020 Sep 4;9(5):3070-3077. Epub 2020 Aug 4.

Department of Pharmacy, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.

Background: More than half of cancer patients affected by cancer experience pain of moderate-tosevere intensity. Therefore, facilitating appropriate and safe administration of analgesics is crucial to the comprehensive management of cancer patients. In this article, we assessed medication adherence, pain relief, drug related problems (DRPs) and analgesics adverse events (AEs) in cancer pain patients based on a model of clinical pharmacy services.

Methods: In this prospective, single-arm intervention study, cancer pain patients admitted to our institution were eligible. According to different adherence, heterogeneity of pain, and individual treatment strategy, clinical pharmacists (CPs) provided comprehensive pain assessment and medication education for patients, as well as provided consultation and recommendation for physicians. CPs' pharmacy services were assessed through medication adherence, numbers of DRPs, acceptance of recommendation, pain intensity (PI), daily interference and AEs.

Results: A total of 42 patients were enrolled between November, 2018 and November, 2019. Compared to baseline, patients' medication adherence evaluated with a medication adherence scale showed a significantly improvement at 14 and at 28 days after receiving CPs' interventions (8 score vs. 7 score at 14 days and at 28 days, P<0.01). During the 28-day follow-up, a total of 63 interventions were put forward according to 57 identified DRPs in 33 patients (78.6%), and approximately 95% (60/63) of the interventions were accepted by physicians. PI and daily interference significantly improved on the third day after the interventions of CPs, and the improvement continued until day 28 (P<0.01). AEs caused by opioids occurred in 19 patients (45.2%), and the most common one was constipation (14 patients, 33.3%).

Conclusions: CPs' comprehensive interventions for cancer pain patients were efficacious in improving their medication adherence and pain relief, as well as reducing incidence of AEs. Therefore, this promising model should be replicated in other medical centers.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21037/apm-20-627DOI Listing
September 2020

The Successful Rapid Adjustment of Blood Glucose in a Patient With Acute Coronary Syndrome, Renal Insufficiency, and Diabetes: A Case Report of Management Coordinated by Clinical Pharmacists and Clinicians.

Front Pharmacol 2020 21;11:756. Epub 2020 May 21.

Department of Pharmacy, Clinical Research Center, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fphar.2020.00756DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7253704PMC
May 2020

Net clinical benefit of antithrombotic therapy in patients with heart failure and sinus rhythm: A network meta-analysis from 5 clinical trials.

Thromb Res 2020 06 18;190:122-128. Epub 2020 Apr 18.

Department of Pharmacy, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China. Electronic address:

Background: Heart failure (HF) is associated with an increased incidence of thromboembolic events. Antithrombotic treatment could reduce the stroke risk, whereas increase the bleeding risk. Whether antithrombotic treatment should be a routine therapy for HF and sinus rhythm (SR) patients remains unanswered.

Methods: We systematically searched Medline, Embase, Cochrane Library databases, and ClinicalTrials.gov Website for randomized controlled trials (RCTs) studying antithrombotic therapy in HF and SR patients. The primary outcomes of efficacy and safety were defined as stroke and major bleeding, respectively. The network meta-analysis was conducted. The results were expressed as relative risks (RRs) with 95% confidence intervals (95% CIs), and pooled using a random-effects model. The surface under the cumulative ranking curves (SUCRA) was calculated and trade-off analysis of net clinical benefit (NCB) was estimated.

Results: Five studies totally involving 9390 patients were included. A significantly decreased risk of stroke was found for patients with HF and SR, when rivaroxaban was compared with placebo (RR: 0.67, 95%CI: 0.47-0.96) and warfarin was compared with antiplatelets (RR: 0.49, 95%CI: 0.33-0.73). Warfarin (RR: 7.96, 95%CI: 1.06-59.88) and rivaroxaban (RR: 1.65, 95%CI: 1.16-2.33) were associated with a significant increase in the risk of major bleeding when compared with placebo. Considering the ranking of each antithrombotic therapy for primary outcomes, warfarin (SUCRA: 78.2) emerged with the highest cumulative ranking probability for stroke, with rivaroxaban (SUCRA: 73.9) and antiplatelet agents (SUCRA: 19.6) ranked behind. In terms of major bleeding, rivaroxaban (SUCRA: 57.6) was the safer intervention compared with antiplatelet agents (SUCRA: 43.5) or warfarin (SUCRA: 2.9). No difference was observed considering all-cause death, MI and hospitalization of HF among all different antithrombotic regimens. Rivaroxaban was considered as a reasonably effective and the safe antithrombotic agent for HF and SR patients.

Conclusions: Rivaroxaban might the optimal antithrombotic regimen balancing stroke and major bleeding for HF patients with SR. The results might support the attempt to anticoagulation on HF and SR patients. However, further specialized designs of RCTs are necessary to draw a robust conclusion.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.thromres.2020.04.017DOI Listing
June 2020

Efficacy and safety of current therapeutic options for COVID-19 - lessons to be learnt from SARS and MERS epidemic: A systematic review and meta-analysis.

Pharmacol Res 2020 07 30;157:104872. Epub 2020 Apr 30.

Department of Pharmacy, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 200127, China. Electronic address:

The rapidly progressing of coronavirus disease 2019 (COVID-19) pandemic has become a global concern. This meta-analysis aimed at evaluating the efficacy and safety of current option of therapies for severe acute respiratory syndrome (SARS), Middle Eastern respiratory syndrome (MERS) besides COVID-19, in an attempt to identify promising therapy for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infected patients. We searched PubMed, EMBASE, Cochrane Library, China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (VIP), and WANFANG DATA for randomized controlled trials (RCTs), prospective cohort, and retrospective cohort studies that evaluated therapies (hydroxychloroquine, lopinavir/ritonavir-based therapy, and ribavirin-based therapy, etc.) for SARS, MERS, and COVID-19. The primary outcomes were mortality, virological eradication and clinical improvement, and secondary outcomes were improvement of symptoms and chest radiography results, incidence of acute respiratory disease syndrome (ARDS), utilization of mechanical ventilation, and adverse events (AEs). Summary relative risks (RRs) and 95% confidence intervals (CIs) were calculated using random-effects models, and the quality of evidence was appraised using GRADEpro. Eighteen articles (5 RCTs, 2 prospective cohort studies, and 11 retrospective cohort studies) involving 4,941 patients were included. Compared with control treatment, anti-coronary virus interventions significantly reduced mortality (RR 0.65, 95% CI 0.44-0.96; I = 81.3%), remarkably ameliorate clinical improvement (RR 1.52, 95% CI 1.05-2.19) and radiographical improvement (RR 1.62, 95% CI 1.11-2.36, I = 11.0 %), without manifesting clear effect on virological eradication, incidence of ARDS, intubation, and AEs. Subgroup analyses demonstrated that the combination of ribavirin and corticosteroids remarkably decreased mortality (RR 0.43, 95% CI 0.27-0.68). The lopinavir/ritonavir-based combination showed superior virological eradication and radiographical improvement with reduced rate of ARDS. Likewise, hydroxychloroquine improved radiographical result. For safety, ribavirin could induce more bradycardia, anemia and transaminitis. Meanwhile, hydroxychloroquine could increase AEs rate especially diarrhea. Overall, the quality of evidence on most outcomes were very low. In conclusion, although we could not draw a clear conclusion for the recommendation of potential therapies for COVID-19 considering the very low quality of evidence and wide heterogeneity of interventions and indications, our results may help clinicians to comprehensively understand the advantages and drawbacks of each anti-coronavirus agents on efficacy and safety profiles. Lopinavir/ritonavir combinations might observe better virological eradication capability than other anti-coronavirus agents. Conversely, ribavirin might cause more safety concerns especially bradycardia. Thus, large RCTs objectively assessing the efficacy of antiviral therapies for SARS-CoV-2 infections should be conducted with high priority.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.phrs.2020.104872DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7192121PMC
July 2020

Rationale and design of a prospective multi-center randomized trial of EARLY treatment by rivaroxaban versus warfarin in ST-segment elevation MYOcardial infarction with Left Ventricular Thrombus (EARLY-MYO-LVT trial).

Ann Transl Med 2020 Mar;8(6):392

Department of Cardiology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 200127 Shanghai, China.

Background: Left ventricular thrombus (LVT), a common complication of acute ST-segment elevation myocardial infarction (STEMI), is associated with increased risk of systemic embolism and high mortality. Current STEMI guidelines recommend adding anticoagulant therapy to dual antiplatelet therapy (DAPT) if early-formulated LVT were detected, for which vitamin K antagonist (VKA) is the standard anticoagulant agent. The role of non-VKA oral anticoagulants (NOACs) in this scenario is uncertain.

Methods: The EARLY-MYO-LVT study will be a prospective, multi-center and randomized trial designed to investigate the efficacy and safety of rivaroxaban versus warfarin in the treatment of post-STEMI LVT. It will enroll 280 patients with STEMI who have developed LVT within the first month of symptom onset. They will be randomized at 1:1 ratio into the group of rivaroxaban 15 mg daily or VKA treatment (with targeted INR 2-2.5) on the basis of standard DAPT (100 mg daily aspirin plus 75 mg daily clopidogrel) for 3-6 months. The primary efficacy endpoint will be the probability of LVT resolution after 3-month triple therapy, and the principal safety outcome will be the incidence of major bleeding events during the treatment.

Discussion: The described study will systemically assess the efficacy and safety of NOACs-based anticoagulant therapy in the treatment of LVT subsequent to STEMI.

Trial Registration: The EARLY-MYO-LVT trial (Clinical trial number: NCT03764241).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21037/atm.2020.02.117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7186620PMC
March 2020

Comparison of effectiveness and safety of direct oral anticoagulants versus vitamin-k antagonists in elderly patients with atrial fibrillation: a systematic review and cost-effectiveness analysis protocol.

Ann Transl Med 2020 Mar;8(6):391

Department of Pharmacy, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China.

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).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21037/atm.2020.02.109DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7186719PMC
March 2020

Initial anticoagulation experience with standard-dose rivaroxaban after Watchman left atrial appendage occlusion.

Ann Transl Med 2020 Feb;8(4):105

Department of Cardiology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China.

Background: Warfarin is now recommended as the standard anti-thrombotic regimen to allow complete endothelialization over the Watchman device post percutaneous left atrial appendage occlusion (LAAO). However, the need for frequent monitoring, narrow therapeutic range, dietary restrictions and multiple drug interactions associated with warfarin have contributed to increasing uptake of non-vitamin K oral anticoagulants (NOACs) worldwide. At present, the feasibility and safety of NOACs instead of warfarin post-LAAO is lacking.

Methods: Patients who underwent successful Watchman device implantation between October 1, 2016 and September 30, 2017 were enrolled in a retrospective database. And only patients who received rivaroxaban in the periprocedural period were included in this study. Transesophageal echocardiography (TEE) follow-up was scheduled at 6 weeks, at 6 months, and at 12 months post-implantation to detect device-related thrombosis (DRT) or peri-device leak. Meanwhile, thromboembolic and bleeding events were also evaluated at the time of follow-up.

Results: Totally, 57 Watchman devices were successfully implanted and 10 patients who were allocated to rivaroxaban at the dosage of 20 mg once daily were included. During the follow-up, none of the patients using rivaroxaban experienced DRT, peri-device leak, thromboembolic complications and major bleeding events, except for 2 patients who suffered minor bleeding during the 6 weeks follow-up.

Conclusions: This study suggests that a short course of standard-dose rivaroxaban following Watchman LAAO is associated with low incidence of thrombotic complications and bleeding events, and might be a feasible alternative regimen in Chinese. Further randomized trials and large sample of real-world studies are needed to validate our finding.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21037/atm.2019.12.116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7048987PMC
February 2020

Direct versus conventional anticoagulants for treatment of cancer associated thrombosis: a pooled and interaction analysis between observational studies and randomized clinical trials.

Ann Transl Med 2020 Feb;8(4):95

Department of Pharmacy, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200127, China.

Background: There are emerging observational studies (OSs) to assess real-world comparative effectiveness and safety of direct oral anticoagulants (DOACs) in cancer associated thrombosis (CAT). We conducted a pooled and interaction analysis to compare the treatment effect estimates of DOACs between OSs and randomized controlled trials (RCTs).

Methods: We systematically searched PUBMED, EMBASE and Cochrane Library for OSs and RCTs that reported recurrent venous thromboembolism (VTE) and/or major bleeding events in CAT patients receiving DOACs and conventional anticoagulants [warfarin or low molecular-weight heparins (LMWHs)]. Relative risks (RRs) for OSs and RCTs were calculated using random-effects models separately, and interaction analyses were afterward applied to assess the comparability between OSs and RCTs.

Results: Baseline characteristic was comparable between identified 10 OSs (35,142 patients) and 8 RCTs (2,602 patients). Overall, no significant difference of treatment effect estimates between OSs and RCTs was detected (P: 0.42 for recurrent VTE; P: 0.38 for major bleeding). DOACs significantly decreased the risk of recurrent VTE compared with conventional anticoagulants in CAT patients (RR: 0.74, 95% CI: 0.63-0.86, I: 0% for OSs; RR: 0.65, 95% CI: 0.49-0.86; I: 0% for RCTs), without increasing major bleeding risk (RR: 0.90, 95% CI: 0.76-1.07, I: 24.0% for OSs; RR: 1.17, 95% CI: 0.72-1.88, I: 26.2% for RCTs). Whereas, increased risk of gastrointestinal bleeding (GIB) was found with DOACs versus conventional anticoagulants in CAT patients (RR: 2.77, 95% CI: 1.35-5.68, I: 0% for RCTs). Analyses of subgroups, based on comparators and follow-up duration, did not significantly affect results.

Conclusions: In this study, effectiveness and safety of DOACs versus conventional anticoagulants in CAT from OSs are in agreement with those from RCTs, confirming a low risk of recurrent VTE and similar risk of major bleeding in CAT patients receiving DOACs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21037/atm.2019.12.152DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7049023PMC
February 2020

MicroRNA expression signatures of atrial fibrillation: The critical systematic review and bioinformatics analysis.

Exp Biol Med (Maywood) 2020 01 25;245(1):42-53. Epub 2019 Nov 25.

Department of Pharmacy, Affiliated Hospital of Shaoxing University, Shao Xing 312000, China.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/1535370219890303DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6987745PMC
January 2020

Net clinical benefit of non-vitamin K antagonist oral anticoagulants in atrial fibrillation and chronic kidney disease: a trade-off analysis from four phase III clinical trials.

Cardiovasc Diagn Ther 2019 Oct;9(5):410-419

Department of Pharmacy, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200127, China.

Background: Atrial fibrillation (AF) is quite prevalent in patient with chronic kidney disease (CKD). This study mainly investigated the net clinical benefit (NCB) property of non-vitamin K antagonist oral anticoagulants (NOACs) versus warfarin in patients with AF and CKD by a pooled-analysis.

Methods: A comprehensive search of Medline, Embase, Cochrane Library and Clinical Trials.gov Website was performed for eligible randomized controlled trials (RCTs) reporting the efficacy and safety outcomes according to renal function of NOACs. Pre-specified outcomes and their number of patients needed to treat (NNT), including stroke/systemic embolism (SSE), major bleeding, and all-cause death, were evaluated using a random-effects model. NCB that balanced SSE and major bleeding was calculated using Singer's method.

Results: Four phase III clinical trials including 70,952 patients were enrolled, 45,265 (64%) with CKD, and 25,687 (36%) without CKD; 41,942 (59%) taking NOACs and 29,010 (41%) taking warfarin. Risks of SSE [relative risk (RR): 0.80, 95% confidence interval (CI): 0.73-0.88, P<0.01], major bleeding (RR: 0.79, 95% CI: 0.66-0.96, P=0.017), and all-cause death (RR: 0.91, 95% CI: 0.84-0.99, P=0.031) were significantly lower in CKD patients with NOACs than those with warfarin, accompanying with a high absolute risk reduction (NNT: 182 for SSE; 122 for major bleeding; 196 for all-cause death). While NOACs were not superior to warfarin on SSE, major bleeding, and all-cause death in patients without CKD, the NCB of NOACs versus warfarin was progressively increased with the deterioration of renal function (NCB: 0.72 for no CKD, 1.59 for mild CKD, 2.74 for moderate CKD). Sensitivity analyses did not significantly affect the primacy results.

Conclusions: NOACs, compared with warfarin, provide a better clinical profile on SSE, major bleeding, all-cause death, and NCB in CKD patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21037/cdt.2019.07.09DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6837910PMC
October 2019

Clinical pharmacist intervention reduces mortality in patients with acute myocardial infarction: a propensity score matched analysis.

Eur J Hosp Pharm 2019 Sep 14;26(5):248-252. Epub 2018 Mar 14.

Department of Pharmacy, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.

Background: Is it possible that the mortality rate from acute myocardial infarction (AMI) may decline after interventions by pharmacists?

Objective: To evaluate the impact of clinical pharmacist on the mortality of AMI.

Methods: Clinical pharmacists did not perform any interventions during phase 1 (pre-intervention), and consulted with physicians to address drug related problems (DRPs) during phase 2 (post-intervention). The main outcome was a decrease in mortality from AMI. The two phases were compared using propensity score matching (PSM).

Results: 1388 interventions were suggested by clinical pharmacists during phase 2, of which 1239 (89.2%) were accepted. Logistic regression analysis demonstrated that interventions of clinical pharmacists were significantly associated with a reduced mortality in patients with both ST segment elevation myocardial infarction (STEMI) (OR 0.449; 95% CI 0.296 to 0.680) and non-ST segment elevation myocardial infarction (NSTEMI) (OR 0.268; 95% CI 0.125 to 0.572). Using PSM analysis, mortality reduced from 6.8% to 4.3% in STEMI patients (P=0.0034) and from 3.2% to 0.7% in NSTEMI patients (P=0.0202) after the interventions.

Conclusions: DRPs that caused or contributed to possible mortality were detected by clinical pharmacists in patients with AMI. Correcting these DRPs after pharmacists' interventions could result in a significant decrease in mortality.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/ejhpharm-2017-001344DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6788265PMC
September 2019

Appraisal of Non-Cardiovascular Safety for Sodium-Glucose Co-Transporter 2 Inhibitors: A Systematic Review and Meta-Analysis of Placebo-Controlled Randomized Clinical Trials.

Front Pharmacol 2019 19;10:1066. Epub 2019 Sep 19.

Department of Pharmacy, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Whereas the cardiovascular safety of sodium-glucose co-transporter 2 (SGLT2) inhibitors has been well reported, there is limited data from controlled clinical trials regarding the non-cardiovascular safety. This was the focus of our study. We systematically searched MEDLINE, EMBASE, and Cochrane Library (5 Sep 2018) for randomized controlled trials (RCTs) that reported safety data for SGLT2 inhibitors and placebo. Relative risks (RRs) and their 95% confidence intervals (CIs) were pooled using random-effects models. Seventy RCTs (83 studies enrolling 36,958 patients in 78 publications) were identified. SGLT2 inhibitors were associated with a lower risk of serious adverse events (RR 0.90, 95% CI 0.86 to 0.94, < 0.001), death (RR 0.78, 95% CI 0.64 to 0.94, < 0.05), gastroenteritis (RR 0.38, 95% CI 0.20 to 0.72, < 0.05), arthralgia (RR 0.72, 95% CI 0.54 to 0.96, < 0.05), hypertension (RR 0.61, 95% CI 0.50 to 0.75, < 0.001), and edema/peripheral edema (RR 0.49, 95% CI 0.33 to 0.72, < 0.001) compared to placebo. SGLT2 inhibitors were associated with higher risk of infections compared to placebo (RR 1.27, 95% CI 1.17 to 1.37, < 0.001), especially for genital mycotic infection (GMI) (RR 3.71, 95% CI 3.19 to 4.32, < 0.001). Other significant effects were observed for osmotic diuresis-related AEs (RR 2.73, 95% CI 2.20 to 3.40, < 0.001), volume-related AEs (RR 1.26, 95% CI 1.08 to 1.46, < 0.05), renal-related AEs (RR 1.36, 95% CI 1.02 to 1.80, < 0.05), hypoglycemia (RR 1.18, 95% CI 1.10 to 1.26, < 0.001), and increased blood ketone bodies (RR 2.00, 95% CI 1.01 to 3.97, < 0.05). Subgroup and sensitivity analyses strengthened the robustness of primary results. Results from RCTs confirmed lower risk of death, serious adverse events, hypertension, and edema associated with type 2 diabetes mellitus (T2DM) patients treated with SGLT2 inhibitors when compared with placebo. The use of SGLT2 inhibitors were associated with higher risk of infection, osmotic diuresis, volume depletion effects, renal related AEs, and higher blood ketone bodies when compared with placebo.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fphar.2019.01066DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6764217PMC
September 2019

Minimal change disease induced by tiopronin: a rare case report and a review of the literature.

Ann Transl Med 2019 Aug;7(16):398

Department of Pharmacy, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200127, China.

Tiopronin (TP), a glycine derivative with a free thiol, is extensively used for the treatment of cystinuria. Moreover, TP is usually prescribed as hepatoprotective medicine in China. In the present case, a 36-year-old female who presented with foamy urine and general edema was admitted to the hospital. She had been taking TP for six months to treat drug-induced liver injury due to anti-tuberculosis drugs including isoniazid, rifampicin and pyrazinamide. The urine tests at admission revealed nephritic-range proteinuria with a daily urinary protein level of 8,024 mg. Meanwhile, albumin and cholesterol levels were abnormal. The light microscopy was negative and electron microscopy showed foot process effacement. Thus, minimal change disease (MCD) was diagnosed, and TP was consequently discontinued. Finally, the patient accomplished complete remission within five weeks after the cessation of TP without undergoing glucocorticoid therapy. TP was speculated to play an antigenic role in this adverse effect. To date, there are only two similar cases documented in the literature. Herein, we first report a case of a Chinese patient who generated MCD after prolonged TP administration. Clinicians should be wary of the occurrence of MCD due to TP when administering long-term therapy of TP. A weekly urinalysis may be useful for early identification of TP-induced MCD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21037/atm.2019.07.42DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6736807PMC
August 2019

Identification of microRNA biomarkers in atrial fibrillation: A protocol for systematic review and bioinformatics analysis.

Medicine (Baltimore) 2019 Jul;98(30):e16538

Department of Pharmacy.

Background: Atrial fibrillation (AF) is recognized as the most prevalent arrhythmia, and its subsequently serious complications of heart failure and thromboembolism always raise the social attention. To date, the molecular pathogenesis of AF has largely remained unclear. Publications of contemporary studies have evaluated individual miRNAs expression signatures for AF, and findings of different studies are inconsistent and not all miRNAs reported are actually important in the pathogenesis of AF.

Methods: Medline, Embase, and Cochrane Library databases will be comprehensively searched (up to April 30, 2019) for studies identifying miRNA expression profiling in subjects with and without AF. Log10 odds ratios (logORs) and associated 95% confidence interval (95%CI) will be calculated using random-effects models. Subgroup analysis will be performed according to miRNA detecting methods, species, sample types, and ethnicities. Sensitivity analysis will be conducted to detect the robustness of the findings. The methodological quality of studies will be independently assessed using criteria adopted from the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2). Furthermore, bioinformatics analysis will be performed to identify the potential target genes in AF and the corresponding pathways of dysregulated miRNAs. Two reviewers will independently screen potential studies and extract data in a structured eligibility items, with any disagreements being resolved by consensus.

Results: The present systematic review will identify potential biomarkers by pooling all differentially expressed miRNAs in AF studies, as well as to predict miRNA-target interactions and to identify the potential biometric functions using bioinformatics analysis.

Conclusions: This systematic review and bioinformatics analysis will identify several miRNAs as potential biomarkers for AF, and explore the biological pathways regulated by the eligible miRNAs.

Prospero Registration Number: CRD42019127594.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MD.0000000000016538DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6708903PMC
July 2019