Efficacy of Therapeutic Dose Versus Prophylactic Dose of Anticoagulants in the Primary Prevention of Thrombotic Events in Ambulatory Patients with Solid Malignancies Receiving Chemotherapy: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Abstract Background: Vascular thromboembolism (VTE) is a recognized complication of cancer. Clinical trials have demonstrated varying degrees of efficacy of antithrombotic agents in preventing VTE in patients suffering from cancer. Benefit of anticoagulants was found to be more pronounced among patients who are at a higher risk for VTE such as patients with advanced cancer and patients undergoing chemotherapy and/or radiotherapy. However, the optimal dose of anticoagulants used in these settings remains unknown. Therefore, we have performed a systematic review and meta-analysis of randomized controlled trials (RCT) to evaluate the efficacy of different dosing of anticoagulants in the primary prevention of VTE among patients with advanced solid malignancies receiving chemotherapy. Methods: We undertook an extensive electronic database search using PUBMED and EMBASE databases for eligible studies. RCTs, involving patients with advanced solid malignancies receiving chemotherapy, which reported VTE rates as a primary or secondary outcome were included. RCTs that had a mixed population of patients such as all stages of cancer, solid and hematologic cancers, and chemotherapy and non-chemotherapy patients were excluded. The primary outcomes in this analysis were all reported VTE events and major bleeds. The secondary outcome was overall mortality rate. We used Comprehensive Meta-analysis Version 2 (Biostat, Englewood NJ) to estimate the pooled event-based risk ratio (RR) and risk difference (RD) with 95% confidence interval (CI) by using Mantel-Haenszel method. Random effects model was applied because of heterogeneity among the studies. Results: Eight RCTs comprising 6,492 patients (5 RCTs using prophylactic dose (n = 5,556), 1 RCT using semi-therapeutic dose (n = 312), 2 RCTs using therapeutic dose (n = 624)) are eligible for analysis. The duration of thromboprophylaxis ranged from 6 weeks to 6 months. The crude VTE rates were 2.65% and 5.66% in thromboprophylaxis and control groups, respectively, with an overall RR of 0.48 (CI = 0.36 – 0.64). RRs for VTE in patients receiving prophylactic, semi-therapeutic and therapeutic doses of anticoagulants were 0.48 (CI = 0.33 – 0.68), 0.35 (CI = 0.16 – 0.75) and 0.62 (CI = 0.33 – 1.16), respectively. The RRs of these subgroups were not significantly different from one another (p = 0.518). The overall RD was -0.024 (CI = -0.033 – -0.016), suggesting an estimated number needed to treat (NNT) of 42 (CI = 30 – 63) to prevent one VTE event. RRs for major bleeding across different antithrombotic doses were not statistically different (p = 0.44) with RRs of 1.1 (CI = 0.69 – 1.75), 0.63 (CI = 0.29 – 1.37) and 1.16 (CI = 0.52 – 2.58) for prophylactic, semi-therapeutic and therapeutic doses, respectively. The overall RR for major bleeding was 0.99 (CI = 0.69 – 1.41). There was no difference in mortality rate between thromboprophylaxis and control groups (RR = 0.98, CI = 0.92 – 1.04, p = 0.42). However, there was a nonsignificant trend towards improvement in mortality in the therapeutic dose subgroup (RR = 0.9, CI = 0.78 – 1.05, p = 0.17). Conclusions: Our meta-analysis demonstrated that, among patients with advanced solid malignancies receiving chemotherapy, primary thromboprophylaxis with anticoagulants significantly reduced VTE events without an increase in major bleeding events compared to control, even though an overall survival benefit was not observed. The benefit in VTE reduction, the risk of major bleeding events and the incidence of overall mortality were similar among the three dosing regimens. However, it was noted that there was a nonsignificant trend towards survival advantage in the therapeutic dose subgroup. Figure 1 Figure 1. Figure 2 Figure 2. Figure 3 Figure 3. Disclosures No relevant conflicts of interest to declare.

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Prophylactic anticoagulant therapy decreases the incidence of deep vein thrombosis in patients with solid tumors: A systematic review and meta-analysis

Journal of Solid Tumors ◽

10.5430/jst.v7n1p35 ◽

2017 ◽

Vol 7 (1) ◽

pp. 35

Author(s):

Yunjiao Zhou ◽

Gong Yang ◽

Chenglei Huang

Keyword(s):

Systematic Review ◽

Deep Vein Thrombosis ◽

Solid Tumors ◽

Risk Ratio ◽

Major Bleeding ◽

Meta Analysis ◽

Bleeding Events ◽

Vein Thrombosis ◽

And Control ◽

Deep Vein

It is not well understood the efficacy and safety of primary deep vein thrombosis (DVT) prophylaxis of anticoagulants in patients with solid tumors. This systematic review and meta-analysis of randomized controlled trials (RCT) determines the relative ratio of primary DVT, survival rate and bleeding events among patients with solid tumors treated with anticoagulants or placebo. Comprehensive literature searches were conducted through the Pubmed, Ovid MEDLINE and EMBASE databases published from January 1st, 1993 to December 31st, 2015. Statistical analysis was performed by RevMan 5.0 software. For DVT events, therisk ratio in 16 trials between the prophylactic and control patients was statistically significant at 0.45 [0.36-0.58]; for major bleeding events, the risk ratio in 18 trials between the prophylactic and control patients was not statistically significant at 1.33 [0.99-1.79], while that in 15 trials with clinically relevant non-major bleeding was statistically significant at 1.83 [1.46-2.30]; the risk ratio for the mortality rate of patients with solid tumors in 16 trials was not statistically significant at 0.97 [0.93-1.02]. Inconclusion, the risk ratio in this meta-analysis showed a significantly reduced incidence of DVT with anticoagulant use. Treatment to patients who had solid tumors with prophylactic anticoagulants enhanced the incidence rate of non-major bleeding but has no significant impact on the incidence rate of major bleeding. No significant differences were found in the mortality outcomes between anticoagulant and non-anticoagulant groups.

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A meta-analysis of anticoagulants as cancer treatment: Impact on survival and bleeding complications

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.9071 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 9071-9071

Author(s):

N. M. Kuderer ◽

A. A. Khorana ◽

G. H. Lyman ◽

C. W. Francis

Keyword(s):

Relative Risk ◽

Cancer Patients ◽

Major Bleeding ◽

Meta Analysis ◽

Bleeding Complications ◽

Primary Study ◽

Bleeding Events ◽

Impact On Survival ◽

The Impact ◽

Overall Mortality

9071 Background: There is substantial laboratory evidence that anticoagulants, in particular the low-molecular-weight heparins (LMWH), exert an antitumor effect, while clinical trials have reported conflicting results. This study represents the first comprehensive systematic review and meta-analysis of the evidence from randomized controlled trials (RCTs) evaluating specifically the impact of anticoagulants on survival and safety in cancer patients without venous thromboembolism (VTE). Methods: An exhaustive systematic literature review of RCTs was performed without language restrictions, including a comprehensive search of electronic databases through May 2006 with subsequent weekly updates to the end of 2006 (Medline, EMBASE, Cochrane Database of Systematic Reviews, CENTRAL, DARE, and major conference proceedings) and relevant article references. Two reviewers extracted the data independently. Primary study outcomes were 1-year overall mortality and all bleeding complications. Major and fatal bleeding complications were secondary outcomes. The meta- analysis was performed utilizing the Mantel-Haenszel method. Results: All identified 11 RCTs were performed in solid tumor patients. Anticoagulation significantly decreased overall mortality across all studies with a relative risk (RR) of 0.905 (95%CI: 0.847–0.967; p=0.003). The survival improvement appears not to be due to the prevention of fatal VTE. All bleeding complications (RR=2.309; 95%CI: 1.928–2.764; p<0.0001) and major bleeding events (RR=2.598; 95%CI; 1.936–3.488; p<0.0001) occurred more frequently with anticoagulation. The relative risk for mortality was 0.877 (95%CI: 0.789–0.975; p=0.015) with LMWH, compared to warfarin (RR=0.942; 95%CI: 0.854–1.040; p=0.239). Warfarin resulted in higher rates for all and major bleeding complications compared to LMWH (p<0.0001, respectively). Conclusions: Anticoagulants significantly improved overall survival in cancer patients while increasing the risk of bleeding complications. Despite these encouraging findings, given limitations of available data and the potential for life-threatening complications, the use of anticoagulants as antineoplastic therapy cannot be recommended until additional RCTs confirm these results. No significant financial relationships to disclose.

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Anticoagulation and In-Hospital Mortality From Coronavirus Disease 2019: A Systematic Review and Meta-Analysis

Clinical and Applied Thrombosis/Hemostasis ◽

10.1177/10760296211008999 ◽

2021 ◽

Vol 27 ◽

pp. 107602962110089

Author(s):

Chatphatai Moonla ◽

Darintr Sosothikul ◽

Thita Chiasakul ◽

Ponlapat Rojnuckarin ◽

Noppacharn Uaprasert

Keyword(s):

Hospital Mortality ◽

Major Bleeding ◽

Therapeutic Dose ◽

Meta Analysis ◽

Cochrane Library ◽

Efficacy And Safety ◽

Random Effects Models ◽

Prophylactic Dose ◽

Anticoagulated Patients ◽

Overall Mortality

Hypercoagulability in coronavirus disease 2019 (COVID-19) may aggravate disease severity during hospitalization but the reported survival benefits from anticoagulation (AC) vary among studies. We performed a literature research to estimate pooled odds ratios (ORs) of in-hospital mortality and major bleeding comparing among intermediate-to-therapeutic dose AC, prophylactic dose AC, and no AC. Until October 22, 2020, PubMed, EMBASE, and Cochrane Library Database were searched for studies reporting AC utilization and mortality in COVID-19. Studies with suspected risk of bias were excluded before the synthesis of pooled ORs with 95% confidence intervals (CIs) using random-effects models. Of 37 identified studies (N = 19,510), 17 (N = 17,833) were aggregated in the meta-analysis. The overall mortality rate was 23.1% (95% CI 18.7-28.2). The pooled odds of mortality comparing anticoagulated to non-anticoagulated patients were similar, but lower in prophylactic dose AC group (OR 0.83; 95% CI 0.73-0.95). Notably, intermediate-to-therapeutic dose AC increased mortality (OR 1.60; 95% CI 1.11-2.31) and major bleeding compared to prophylactic dose AC (OR 3.33; 95% CI 2.34-4.72). Our findings support the optimal efficacy and safety profiles of prophylactic dose AC in hospitalized COVID-19 patients.

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High versus Standard Intensity of Thromboprophylaxis in Hospitalized Patients with COVID-19: A Systematic Review and Meta-Analysis

Journal of Clinical Medicine ◽

10.3390/jcm10235549 ◽

2021 ◽

Vol 10 (23) ◽

pp. 5549

Author(s):

Anastasios Kollias ◽

Konstantinos G. Kyriakoulis ◽

Ioannis P. Trontzas ◽

Vassiliki Rapti ◽

Ioannis G. Kyriakoulis ◽

...

Keyword(s):

Systematic Review ◽

Venous Thromboembolism ◽

Major Bleeding ◽

Therapeutic Dose ◽

Survival Benefit ◽

Meta Analysis ◽

Hospitalized Patients ◽

Bleeding Events ◽

Prophylactic Dose ◽

Major Bleeding Events

Thromboprophylaxis in hospitalized patients with COVID-19 has been associated with a survival benefit and is strongly recommended. However, the optimal dose of thromboprophylaxis remains unclear. A systematic review and meta-analysis (PubMed/EMBASE) of studies comparing high (intermediate or therapeutic dose) versus standard (prophylactic dose) intensity of thrombo-prophylaxis with regard to outcome of hospitalized patients with COVID-19 was performed. Randomized and non-randomized studies that provided adjusted effect size estimates were included. Meta-analysis of 7 studies comparing intermediate versus prophylactic dose of thromboprophylaxis (2 randomized and 5 observational, n = 2009, weighted age 61 years, males 61%, ICU 53%) revealed a pooled adjusted relative risk (RR) for death at 0.56 (95% confidence intervals (CI) 0.34, 0.92) in favor of the intermediate dose. For the same comparison arms, the pooled RR for venous thromboembolism was 0.84 (95% CI 0.54, 1.31), and for major bleeding events was 1.63 (95% CI 0.79, 3.37). Meta-analysis of 17 studies comparing therapeutic versus prophylactic dose of thromboprophylaxis (2 randomized and 15 observational, n = 7776, weighted age 64 years, males 54%, ICU 21%) revealed a pooled adjusted RR for death at 0.73 (95% CI 0.47, 1.14) for the therapeutic dose. An opposite trend was observed in the unadjusted analysis of 15 observational studies (RR 1.24 (95% CI 0.88, 1.74)). For the same comparison arms, the pooled RR for venous thromboembolism was 1.13 (95% CI 0.52, 2.48), and for major bleeding events 3.32 (95% CI 2.51, 4.40). In conclusion, intermediate compared with standard prophylactic dose of thromboprophylaxis appears to be rather safe and is associated with additional survival benefit, although most data are derived from observational retrospective analyses. Randomized studies are needed to define the optimal thromboprophylaxis in hospitalized patients with COVID-19.

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Indicated preventive interventions for anxiety in children and adolescents: a review and meta-analysis of school based programs

10.31234/osf.io/jadxq ◽

2019 ◽

Author(s):

Siobhan Hugh-Jones ◽

Sophie Beckett ◽

Pavan Mallikarjun

Keyword(s):

Meta Analysis ◽

Child And Adolescent ◽

Sensitivity Analyses ◽

Cochrane Library ◽

Control Groups ◽

Adolescent Anxiety ◽

School Based ◽

Intervention Intensity ◽

Randomised Controlled ◽

And Control

Schools are promising sites for the delivery of prevention and early intervention programs to reduce child and adolescent anxiety. It is unclear whether universal or targeted approaches are most effective. This review and meta-analysis examines the effectiveness of school-based indicated interventions and was registered with PROSPERO [CRD42018087628].MEDLINE, EMBASE, PsycINFO and the Cochrane Library were searched for randomised controlled trials comparing indicated school programs for child and adolescent anxiety to active or inactive control groups. Twenty original studies, with 2076 participants, met the inclusion criteria and 18 were suitable for meta-analysis. Sub-group and sensitivity analyses explored intervention intensity, delivery agent and control type. A small beneficial effect was found for indicated programs compared to controls on self-reported anxiety symptoms at post-test (g = -0.28, CI = -0.50, -0.05, k= 18). The small effect was maintained at 6 (g = -0.35, CI= -0.58, -0.13, k = 9) and 12 months (g = -0.24, CI = -0.48, 0.00, k = 4). Based on two studies, >12 month effects were very small (g = -0.01, CI= -0.38, 0.36). No differences were found based on intervention intensity, delivery agent and control type. There was evidence of publication bias and a relatively high risk of contamination in studies. Findings support the value of school based indicated programs for child and adolescent anxiety. Effects at 12 months outperform many universal programs. High quality, randomised controlled and pragmatic trials are needed, with attention control groups and beyond 12 month diagnostic assessments are needed.

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Immersive Virtual Reality Improves Labor and Delivery Experience for Women: A Randomized Controlled Trial

10.21203/rs.3.rs-898920/v1 ◽

2021 ◽

Author(s):

Elif Gizem Carus ◽

Nazli Albayrak ◽

Selen Gur Ozmen ◽

Halit Mert Bildirici

Keyword(s):

Virtual Reality ◽

Patient Satisfaction ◽

Rating Scale ◽

Secondary Outcome ◽

Immersive Virtual Reality ◽

Labor And Delivery ◽

Control Groups ◽

Randomized Controlled ◽

Pain Scores ◽

And Control

Abstract Objective: To evaluate the effectiveness of immersive Virtual Reality (VR) in laboring women on patient satisfaction as a distractive tool and pain relief.Methods: Randomized, controlled clinical trial with 42 laboring women allocated to VR intervention and control groups. Among the VR group, patient satisfaction with the use of VR was assessed by a Virtual Reality Satisfaction Survey and questioning whether they would choose VR in future labor. As a primary outcome patient satisfaction scores regarding the overall labor and delivery experience were compared between the two groups. A secondary outcome was pain assessed by a visual pain rating scale in the early and active phases of labor in both groups. Psychometric information was also collected from participants in each group using Beck Anxiety Inventory and Beck Depression Inventory. Results: We observed a high level of patient satisfaction with the use of immersive VR during labor. The survey revealed a mean satisfaction score of 89.6 ± 10.8 out of a maximum of 100. 20 out of 21 (95%) women in the VR group stated that they would like to use VR again in future labor. VR improved pain scores in early labor and contributed positively to overall labor and delivery experience. The mean pain score pre-VR was 2.6±1.2 compared to 2.0±1.3, post-VR, respectively (p<0.01). Anxiety and depression scores were similar in the intervention and control groups (p=0.103, p=0.13, respectively). Conclusion: Immersive VR application during labor was feasible and associated with higher patient satisfaction based on our study. VR also improved pain scores in early labor before epidural placement. Immersive VR may find a place as an adjunct in Labor and Delivery Units to improve the lengthy labor experience for women. Larger studies are needed to confirm these observations. Trial Registration: ClinicalTrials.gov: NCT05032456 / 02/09/2021https://clinicaltrials.gov/ct2/show/NCT05032456

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Impact of ascorbic acid in reducing the incidence of vancomycin associated nephrotoxicity in critically ill patients: A preliminary randomized controlled trial

F1000Research ◽

10.12688/f1000research.55619.1 ◽

2021 ◽

Vol 10 ◽

pp. 929

Author(s):

Nouran Hesham El-Sherazy ◽

Naglaa Samir Bazan ◽

Sara Mahmoud Shaheen ◽

Nagwa A. Sabri

Keyword(s):

Ascorbic Acid ◽

Critically Ill ◽

Critically Ill Patients ◽

Statistical Significance ◽

Intervention Group ◽

Secondary Outcome ◽

Control Group ◽

Control Groups ◽

The Absolute ◽

And Control

Background Antioxidants show nephroprotective effect against vancomycin associated nephrotoxicity (VAN) in animals. This study aimed to assess the ascorbic acid nephro-protective role against VAN clinically. Methods Forty-one critically ill patients were randomly assigned to one of two groups: intervention group (vancomycin IV plus ascorbic acid, n=21) or control group (vancomycin IV only, n=20). Primary outcomes were the incidence of VAN and the absolute change in creatinine parameters, while mortality rate was the secondary outcome. Nephrotoxicity was defined as an increase in serum creatinine (S.cr) by at least 0.5 mg/dL or 50% of baseline for at least two successive measurements. This study is registered at Clinicaltrials.gov (NCT03921099), April 2019. Results Mean absolute S.cr increase was significant when compared between both groups, P-value = 0.036, where S.cr increased by 0.05(0.12) and 0.34(0.55) mg/dL in the intervention and control groups, respectively. Mean absolute Cr.cl decline was significant when compared between both groups, P-value = 0.04, where Cr.cl was decreased by 5.9(17.8) and 22.3(30.4) ml/min in the intervention and control groups, respectively. Incidence of VAN was 1/21(4.7%) versus 5/20(25%) in the intervention and control groups, respectively (RR: 0.19; CI: 0.024–1.49; P-value = 0.093). Mortality was higher in the control group; however, it was not statistically significant, P-value = 0.141. Conclusion Co-administration of ascorbic acid with vancomycin preserved renal function and reduced the absolute risk of VAN by 20.3%, however, the reduction in VAN incidence didn’t reach statistical significance level. Further large multicenter prospective trials are recommended.

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Intermediate-to-therapeutic versus prophylactic anticoagulation for coagulopathy in hospitalized COVID-19 patients: a systemic review and meta-analysis

Thrombosis Journal ◽

10.1186/s12959-021-00343-1 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Sirui Zhang ◽

Yupei Li ◽

Guina Liu ◽

Baihai Su

Keyword(s):

Hospital Mortality ◽

Major Bleeding ◽

Primary Outcome ◽

Meta Analysis ◽

Pooled Analysis ◽

Bleeding Events ◽

Risk Of Bleeding ◽

Therapeutic Anticoagulation ◽

Secondary Outcomes ◽

Prophylactic Anticoagulation

Abstract Background Anticoagulation in hospitalized COVID-19 patients has been associated with survival benefit; however, the optimal anticoagulant strategy has not yet been defined. The objective of this meta-analysis was to investigate the effect of intermediate-to-therapeutic versus prophylactic anticoagulation for thromboprophylaxis on the primary outcome of in-hospital mortality and other patient-centered secondary outcomes in COVID-19 patients. Methods MEDLINE, EMBASE, and Cochrane databases were searched from inception to August 10th 2021. Cohort studies and randomized clinical trials that assessed the efficacy and safety of intermediate-to-therapeutic versus prophylactic anticoagulation in hospitalized COVID-19 patients were included. Baseline characteristics and relevant data of each study were extracted in a pre-designed standardized data-collection form. The primary outcome was all-cause in-hospital mortality and the secondary outcomes were incidence of thrombotic events and incidence of any bleeding and major bleeding. Pooled analysis with random effects models yielded relative risk with 95 % CIs. Results This meta-analysis included 42 studies with 28,055 in-hospital COVID-19 patients totally. Our pooled analysis demonstrated that intermediate-to-therapeutic anticoagulation was not associated with lower in-hospital mortality (RR=1.12, 95 %CI 0.99-1.25, p=0.06, I2=77 %) and lower incidence of thrombotic events (RR=1.30, 95 %CI 0.79-2.15, p=0.30, I2=88 %), but increased the risk of any bleeding events (RR=2.16, 95 %CI 1.79-2.60, p<0.01, I2=31 %) and major bleeding events significantly (RR=2.10, 95 %CI 1.77-2.51, p<0.01, I2=11 %) versus prophylactic anticoagulation. Moreover, intermediate-to-therapeutic anticoagulation decreased the incidence of thrombotic events (RR=0.71, 95 %CI 0.56-0.89, p=0.003, I2=0 %) among critically ill COVID-19 patients admitted to intensive care units (ICU), with increased bleeding risk (RR=1.66, 95 %CI 1.37-2.00, p<0.01, I2=0 %) and unchanged in-hospital mortality (RR=0.94, 95 %CI 0.79-1.10, p=0.42, I2=30 %) in such patients. The Grading of Recommendation, Assessment, Development, and Evaluation certainty of evidence ranged from very low to moderate. Conclusions We recommend the use of prophylactic anticoagulation against intermediate-to-therapeutic anticoagulation among unselected hospitalized COVID-19 patients considering insignificant survival benefits but higher risk of bleeding in the escalated thromboprophylaxis strategy. For critically ill COVID-19 patients, the benefits of intermediate-to-therapeutic anticoagulation in reducing thrombotic events should be weighed cautiously because of its association with higher risk of bleeding. Trial registration The protocol was registered at PROSPERO on August 17th 2021 (CRD42021273780). Graphical abstract

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Efficacy and Safety of Long‐Term Antithrombotic Strategies in Patients With Chronic Coronary Syndrome: A Network Meta‐analysis of Randomized Controlled Trials

Journal of the American Heart Association ◽

10.1161/jaha.120.019184 ◽

2021 ◽

Author(s):

Houyong Zhu ◽

Xiaoqun Xu ◽

Xiaojiang Fang ◽

Fei Ying ◽

Liuguang Song ◽

...

Keyword(s):

Risk Factors ◽

High Risk ◽

Major Bleeding ◽

Meta Analysis ◽

Efficacy And Safety ◽

Bleeding Events ◽

Coronary Syndrome ◽

High Risk Factors ◽

Cerebrovascular Events

Background Long‐term antithrombotic strategies for patients with chronic coronary syndrome with high‐risk factors represent an important treatment dilemma in clinical practice. Our aim was to conduct a network meta‐analysis to evaluate the efficacy and safety of long‐term antithrombotic strategies in patients with chronic coronary syndrome. Methods and Results Four randomized studies were included (n=75167; THEMIS [Ticagrelor on Health Outcomes in Diabetes Mellitus Patients Intervention Study], COMPASS [Cardiovascular Outcomes for People Using Anticoagulation Strategies], PEGASUS‐TIMI 54 [Prevention of Cardiovascular Events in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin–Thrombolysis in Myocardial Infarction 54], and DAPT [Dual Anti‐platelet Therapy]). The odds ratios (ORs) and 95% CIs) were calculated as the measure of effect size. The results of the network meta‐analysis showed that, compared with aspirin monotherapy, the ORs for trial‐defined major adverse cardiovascular and cerebrovascular events were 0.86; (95% CI, 0.80–0.93) for ticagrelor plus aspirin, 0.89 (95% CI, 0.78–1.02) for rivaroxaban monotherapy, 0.74 (95% CI, 0.64–0.85) for rivaroxaban plus aspirin, and 0.72 (95% CI, 0.60,–0.86) for thienopyridine plus aspirin. Compared with aspirin monotherapy, the ORs for trial‐defined major bleeding were 2.15 (95% CI, 1.78–2.59]) for ticagrelor plus aspirin, 1.51 (95% CI, 1.23–1.85) for rivaroxaban monotherapy, and 1.68 (95% CI, 1.37–2.05) for rivaroxaban plus aspirin. For death from any cause, the improvement effect of rivaroxaban plus aspirin was detected versus aspirin monotherapy (OR, 0.76; 95% CI, 0.65–0.90), ticagrelor plus aspirin (OR, 0.79; 95% CI, 0.66–0.95), rivaroxaban monotherapy (OR, 0.82; 95% CI, 0.69–0.97), and thienopyridine plus aspirin (OR, 0.58; 95% CI, 0.41–0.82) regimens. Conclusions All antithrombotic strategies combined with aspirin significantly reduced the incidence of major adverse cardiovascular and cerebrovascular events and increased the risk of major bleeding compared with aspirin monotherapy. Considering the outcomes of all ischemic and bleeding events and all‐cause mortality, rivaroxaban plus aspirin appears to be the preferred long‐term antithrombotic regimen for patients with chronic coronary syndrome and high‐risk factors.

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The Effectiveness of Tocilizumab in the Treatment of COVID-19 in Adults: A Meta-Analysis of Randomized Controlled Trials.

10.21203/rs.3.rs-551091/v1 ◽

2021 ◽

Author(s):

Chun Chen ◽

ZeMei Zhou ◽

Jing Zhang

Keyword(s):

Randomized Controlled Trials ◽

Hospital Discharge ◽

Meta Analysis ◽

Controlled Trials ◽

Cochrane Central Register ◽

Composite Outcome ◽

Control Groups ◽

Randomized Controlled ◽

Serious Infection ◽

And Control

Abstract Background: Since December 2019, COVID-19 has spread to the world which leads to a global health threat. We aimed to investigate the effectiveness of tocilizumab on COVID-19 patients.Methods: We systematically searched PubMed, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL) and WHO international Clinical Trials Registry Platform (ICTRP) from their inception to March 10, 2021 for randomized controlled trials (RCTs) on tocilizumab supplementation in adults with COVID-19 disease. The primary outcomes were mortality at 28-30 day and 60-day, incidence of mechanical ventilation (MV), composite outcome of death or MV, time to hospital discharge, and intensive care unit (ICU) admissions. A random-effects meta-analysis model was used to pool studies. Results: Eleven studies with a total of 6,579 patients were included in our meta-analysis, of which 3,406 and 3,173 were respectively assigned to the tocilizumab and control groups. Tocilizumab could significantly reduce 28-30 day mortality (RR = 0.89, 95% CI 0.80-0.99, P = 0.04), incidence of MV (RR= 0.79, 95% CI 0.71-0.89, P = 0.0001), composition outcome of MV or death (RR = 0.81, 95% CI 0.72-0.90, P = 0.0002), time to hospital discharge (HR = 1.30, 95% CI 1.16-1.45, P ＜ 0.00001 ), ICU admissions (RR = 0.64, 95% CI 0.47-0.88, P = 0.006), serious infection (RR = 0.61, 95% CI 0.40-0.94, P = 0.02) and events of serious adverse advents (RR = 0.64, 95% CI 0.47-0.86, P = 0.004). There was no significant difference between tocilizumab and control groups in 60-day mortality and adverse events (AEs).Conclusions: Tocilizumab could reduce the short-term mortality, incidence of MV, composite outcome of death or MV, ICU admissions, serious infection and events of serious adverse advents, and shorten the time to hospital discharge in hospitalized patients with COVID-19. The optimal effective dose needs to be confirmed by further studies.

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