Efficacy and safety of low-molecular-weight heparin in patients with sepsis: a meta-analysis of randomized controlled trials.
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ABSTRACT:
SUBMITTER: Fan Y
PROVIDER: S-EPMC4867648 | biostudies-other | 2016
REPOSITORIES: biostudies-other
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Project description:Background: Given their changing pathophysiology, elderly patients carry a high risk of embolism and bleeding events; hence, use of appropriate anticoagulants is very important. Low molecular weight heparin (LMWH) is one of the most widely used anticoagulants although LMWHs differ in their anti-Xa, antithrombin, and anticoagulant activities. To date, no study has directly compared the safety and efficacy of different LMWHs in the elderly. We aimed to compare such differences by conducting a network meta-analysis. Methods: We searched the Pubmed, Embase, and Cochrane databases for randomized controlled trials (RCTs) of LMWHs that included patients ≥60 years old up to July 22, 2020. Safety outcomes included venous thromboembolism (VTE) or VTE-related death, deep thrombus embolism, and pulmonary embolism. Safety outcomes were clinically relevant bleeding, major bleeding, minor bleeding, and all-cause death. We calculated relative ratios (RR) and 95% confidence intervals (CI) for all outcomes. The cumulative ranking probabilities (SUCRA) were conducted to rank the comparative effects and safety of all LMWHs. Results: We included 27 RCTs (30,441 elderly), comprising five LMWHs. LMWH was more effective than placebo in preventing VTE or VTE-related death (RR 0.36, 95% CI 0.25-0.53) but less effective than a novel oral anticoagulant (RR 1.59, 95% CI 1.33-1.91) and safer than acenocoumarol regarding risk of clinically relevant bleeding (RR 0.67, 95% CI 0.49-0.90). However, indirect comparison of efficacy and safety of the five LMWHs showed no significant difference in our network analysis, and the subgroup analyses (such as in patients with deep venous thrombosis, cardiac disease, or age >65 years old) supported the results. The SUCRA showed that tinzaparin performed best in preventing VTE or VTE-related death (SUCRA 68.8%, cumulative probability 42.3%) and all-cause death (SUCRA 84.2%, cumulative probability 40.7%), whereas nadroparin was predominant in decreasing the risk of clinically relevant bleeding (SUCRA 84.8%, cumulative probability 77.0%). Conclusions: On present evidence, there are no significant differences in the efficacy and safety of different LMWHs for the elderly. According to the rank probability analysis, nadroparin seems to be safer for the elderly with a high risk of bleeding, whereas tinzaparin is more effective for those with low bleeding risk.
| S-EPMC8703065 | biostudies-literature
Project description:BACKGROUND:Venous thromboembolism (VTE) is considered a potentially serious complication of knee arthroscopy and leads to conditions such as deep venous thrombosis (DVT) and pulmonary embolism (PE). Low-molecular-weight heparin (LMWH) is widely employed in knee arthroscopy to reduce perioperative thromboembolic complications. However, the efficacy and safety of LMWH in knee arthroscopy remains unclear. METHODS:Seven randomized controlled clinical trials on LMWH in knee arthroscopy were identified and included in this meta-analysis. The main outcomes of the effectiveness (prevention of DVT and PE) and complications (death, major bleeding, and minor bleeding) of LMWH in knee arthroscopic surgery were assessed using Review Manager 5.3 software. RESULTS:The meta-analysis indicated that LMWH prophylaxis comprised 79% of asymptomatic DVT. No association was found in symptomatic VTE (RR: 0.90; 95% confidence interval [CI]: 0.39-2.08; P = 0.80), symptomatic DVT (RR: 0.79; 95% CI: 0.28-2.23; P = 0.66), symptomatic PE (RR: 1.36; 95% CI: 0.37-4.97; P = 0.64) and major bleeding (RR: 0.70; 95% CI: 0.12-3.95; P = 0.68) risk during LMWH prophylaxis were identified. Death was not reported in these studies. Moreover, there was a lower incidence of minor bleeding (RR: 0.64; 95% CI: 0.49 to 0.83; P = 0.001) in the control group than in the LMWH group. CONCLUSION:Compared with the control group, the group treated with LMWH after knee arthroscopy was no association in reducing the symptomatic VTE rate, symptomatic DVT rate or symptomatic PE rate. The symptomatic VTE rate was 0.5% (11/2,166) in the LMWH group versus 0.6% (10/1,713) in the control group. Although the limitations of this meta-analysis cannot be ignored, the results of our study show that LMWH after knee arthroscopy is ineffective. We recommend that LMWH should not be routinely provided for knee arthroscopy. TRIAL REGISTRATION:ClinicalTrials.gov NCT03164746.
| S-EPMC6013230 | biostudies-literature
Project description:The efficacy and safety of bivalirudin (Biva) versus heparin in patients with diabetes mellitus (DM) who undergo percutaneous coronary intervention (PCI) remain controversial. Our meta-analysis was undertaken to evaluate the efficacy and safety of Biva compared with those of heparin in patients with diabetes undergoing PCI.We searched PubMed, EMBASE, Cochrane Library, and Clinical Trials.gov databases for randomized controlled trials (RCTs). The primary efficacy endpoint was the incidence of major adverse cardiovascular events (MACE), and the primary safety endpoint was the incidence of major bleeding. Secondary efficacy endpoints were incidence of net adverse clinical events (NACE), myocardial infarction (MI), and death. The pooled risk ratio (RR) with the corresponding 95% confidence intervals (CIs) were used to assess the efficacy and safety of Biva versus heparin.Eleven RCTs met the inclusion criteria, and 8428 patients were included. No significant difference was observed in the subgroup and overall risk of MACE (RR 0.87; 95% CI 0.74-1.02; P?=?.08; I?=?39%) and NACE (RR 0.81; 95% CI 0.61-1.07; P?=?.14; I?=?71%). Biva had an effect similar to that of heparin on the endpoint of death (RR 0.75; 95% CI 0.56-1.02; P?=?.07; I?=?0) and MI (RR 0.92; 95% CI 0.67-1.26; P?=?.59; I?=?0) but decreased the risk of major bleeding (RR 0.63; 95% CI 0.52-0.75; P?<?.00001; I?=?0%).The use of Biva and heparin is associated with a similar risk of MACE, NACE, death, and MI. Biva decreases the risk of major bleeding more significantly than heparin.
| S-EPMC5521879 | biostudies-other
Project description:BackgroundTo understand the clinical outcomes of selenium therapy in patients with sepsis syndrome, we conducted a meta-analysis of randomized controlled trials (RCT).MethodsA total of 13 RCTs comparing selenium and placebo for patients with sepsis were reviewed systematically.ResultsHowever, we could not detect the association of selenium treatment with a decreased mortality at different time course (relative risk [RR] [95% confidence interval, CI]: 0.94 [0.82-1.06] at day 28; 0.73 [0.36-1.47] at day 90; 1.16 [0.78-1.71] at 6 months; respectively). Selenium supplementation did not show favorable efficacy in the incidence of renal failure, secondary infection or duration of mechanical ventilation (RR [95% CI]: 0.65 [0.41-1.03]; 0.96 [0.87-1.06]; standard mean difference [SMD] [95% CI]: 0.17 [-0.30-0.63]; respectively). Interestingly, we found that selenium therapy was benefit for sepsis patients with reduced duration of vasopressor therapy, staying time in intensive care unit and hospital, and incidence of ventilator-associated pneumonia (SMD [95% CI]: -0.75 [-1.37 to -0.13]; -0.15 [CI: -0.25 to -0.04]; -1.22 [-2.44 to -0.01]; RR [95% CI]: 0.61 [0.42-0.89]; respectively).ConclusionBased on our findings, intravenous selenium supplementation could not be suggested for routine use.
| S-EPMC6831114 | biostudies-literature
Project description:We conducted meta-analyses of findings from randomized, placebo-controlled, short-term trials for acute mania in manic or mixed states of DSM (III-IV) bipolar I disorder in 56 drug-placebo comparisons of 17 agents from 38 studies involving 10,800 patients. Of drugs tested, 13 (76%) were more effective than placebo: aripiprazole, asenapine, carbamazepine, cariprazine, haloperidol, lithium, olanzapine, paliperdone, quetiapine, risperidone, tamoxifen, valproate, and ziprasidone. Their pooled effect size for mania improvement (Hedges' g in 48 trials) was 0.42 (confidence interval (CI): 0.36-0.48); pooled responder risk ratio (46 trials) was 1.52 (CI: 1.42-1.62); responder rate difference (RD) was 17% (drug: 48%, placebo: 31%), yielding an estimated number-needed-to-treat of 6 (all p<0.0001). In several direct comparisons, responses to various antipsychotics were somewhat greater or more rapid than lithium, valproate, or carbamazepine; lithium did not differ from valproate, nor did second generation antipsychotics differ from haloperidol. Meta-regression associated higher study site counts, as well as subject number with greater placebo (not drug) response; and higher baseline mania score with greater drug (not placebo) response. Most effective agents had moderate effect-sizes (Hedges' g=0.26-0.46); limited data indicated large effect sizes (Hedges' g=0.51-2.32) for: carbamazepine, cariprazine, haloperidol, risperidone, and tamoxifen. The findings support the efficacy of most clinically used antimanic treatments, but encourage more head-to-head studies and development of agents with even greater efficacy.
| S-EPMC3055677 | biostudies-other
Project description:BackgroundThis meta-analysis is to evaluate the efficacy and safety of bivalirudin in patients with ST-elevation myocardial infarction (STEMI).MethodsPubMed, Cochrane Library, Embase, CNKI, CBMdisc, and VIP database were searched. Randomized controlled trial (RCT) was selected and the meta-analysis was conducted by RevMan 5.1. The primary efficacy endpoint was the incidence of major adverse cardiovascular events (MACE) and the primary safety endpoint was the incidence of major bleeding. Secondary efficacy endpoints were myocardial infarction (MI), target vessel revascularization (TVR), stent thrombosis (ST), stock, mortality, and thrombocytopenia. The pooled risk ratios (RRs) with the corresponding 95% confidence intervals (CI) were used to assess the efficacy and safety of bivalirudin vs heparin.ResultsSeven RCTs met the inclusion criteria, and 16,640 patients were included. We found that bivalirudin associated with lower risk of mortality (RR?=?1.05; 95% CI?=?0.74-1.49; P?=?.03; I?=?2%), major bleeding (RR?=?0.64; 95% CI?=?0.54-0.75; P?<?.00001; I?=?70%) and thrombocytopenia (RR?=?0.39; 95% CI?=?0.25-0.61; P?<?.0001; I?=?0) compared with heparin. However, the use of bivalirudin increase the risk of MI(RR?=?1.37; 95% CI?=?1.10-1.71; P?=?.004; I?=?25%) and ST(RR?=?1.61; 95% CI?=?1.05-2.47; P?=?.03; I?=?70%) and has similar risk of MACE (RR?=?1.00; 95% CI?=?0.90-1.11; P?=?.97; I?=?16%), TVR (RR?=?1.43; 95% CI?=?0.92-2.22; P?=?.11; I?=?46%) and stock (RR?=?1.43; 95% CI?=?0.92-2.22; P?=?.11; I?=?46%) compared with heparin used in STEMI patients.ConclusionBivalirudin associated with lower risk of mortality, major bleeding and thrombocytopenia compared with heparin. However, the use of bivalirudin increase the risk of MI and ST and has similar risk of MACE, TVR and stock compared with heparin used in STEMI patients.
| S-EPMC7015623 | biostudies-literature
Project description:BackgroundDisseminated intravascular coagulation (DIC) occurs in 30-50% of septic patients and contributes to high mortality in the intensive care unit (ICU). However, there are few proven interventions for coagulation disorder management in sepsis. Experimental and clinical data have demonstrated that sepsis could benefit from unfractionated heparin (UFH) treatment. To date, there are no large multicenter trials to determine the safety and efficacy of UFH in septic patients with suspected DIC.MethodsA multicenter, double-blinded, placebo-controlled randomized trial is designed to recruit 600 patients who met sepsis 3.0 criteria and suspected DIC. Participants will be randomized (1:1) to receive UFH or saline via continuous intravenous administration for 7 days within 6 h of enrolment. The primary outcome is ICU mortality. The secondary outcome includes 28-day all-cause mortality, the improvement of Sequential Organ Failure Assessment scores, and the incidence of major hemorrhage. Investigators, participants, and statisticians will be blinded to the allocation.DiscussionThe HepSIC trial is to evaluate the efficacy and safety of UFH on sepsis-related DIC across different areas of China. The small dosage of UFH administration would offer a new potential approach for treating sepsis-related coagulation disorders.Ethics and disseminationEthical approval was granted by all the ethics committees of 20 participant centers. Results will be disseminated via peer-reviewed publications and presented at conferences.Trial registrationClinicalTrials.gov NCT02654561. Registered on 13 January 2016.
| S-EPMC10759642 | biostudies-literature
Project description:Whether anastrozole has superior effects to tamoxifen for breast cancer remains controversial. Therefore, we conducted this meta-analysis of randomized controlled trials (RCTs) to compare the efficacy and safety of anastrozole versus tamoxifen as adjuvant therapy in breast cancer. A systematic literature search of PubMed, Web of Science, Embase, and Cochrane library were performed to evaluate the survival benefits and toxicity profiles of patients with breast cancer who were treated with anastrozole or tamoxifen. The main outcome measures included disease-free survival (DFS), recurrence-free survival (RFS), overall survival (OS), overall response rate (ORR), and adverse events. Hazard ratios (HRs) or risk ratios (RRs) with 95% confidence intervals (CIs) were pooled using a fixed-effects model or random-effects model. Nine RCTs with a total of 15,300 patients met the inclusion criteria and were included in this meta-analysis. Pooled estimates suggested that, anastrozole was associated with a significantly improvement in DFS (HR=0.72, 95%CI: 0.55-0.94; P=0.016), and ORR (RR=1.21, 95% CI: 1.05-1.39; P=0.009) than tamoxifen. But it did not prolong OS (HR=0.96, 95%CI: 0.77-1.21; P=0.751). Compared with tamoxifen, anastrozole induced a higher incidence of arthralgia (RR=1.55, 95%CI: 1.20-1.99; P=0.001) and bone pain (RR=1.31, 95%CI: 1.05-1.62; P=0.015), as well as a lower incidence of vaginal bleeding (RR=0.51, 95%CI: 0.28-0.93; P=0.029), vaginal discharge (RR=0.31, 95%CI: 0.12-0.82; P=0.017), and thromboembolic events (RR=0.39, 95%CI: 0.28-0.55; P<0.001). Based on the current evidence, patients with breast cancer would benefit from the anastrozole treatment.
| S-EPMC5564654 | biostudies-other
Project description:BackgroundLow molecular weight heparins (LMWH) have been extensively studied and became the treatment of choice for several indications including pulmonary embolism. While their efficacy in hemodialysis is considered similar to unfractionated heparin (UFH), their safety remains controversial mainly due to a risk of bioaccumulation in patients with renal impairment. The aim of this systematic review was to evaluate the safety of LMWH when compared to UFH for extracorporeal circuit (ECC) anticoagulation.MethodsWe used Pubmed, Embase, Cochrane central register of controlled trials, Trip database and NICE to retrieve relevant studies with no language restriction. We looked for controlled experimental trials comparing LMWH to UFH for ECC anticoagulation among end-stage renal disease patients undergoing chronic hemodialysis. Studies were kept if they reported at least one of the following outcomes: bleeding, lipid profile, cardiovascular events, osteoporosis or heparin-induced thrombocytopenia. Two independent reviewers conducted studies selection, quality assessment and data extraction with discrepancies solved by a third reviewer. Relative risk and 95% CI was calculated for dichotomous outcomes and mean weighted difference (MWD) with 95% CI was used to pool continuous variables.ResultsSeventeen studies were selected as part of the systematic. The relative risk for total bleeding was 0.76 (95% CI 0.26-2.22). The WMD calculated for total cholesterol was -28.70 mg/dl (95% CI -51.43 to -5.98), a WMD for triglycerides of -55.57 mg/dl (95% CI -94.49 to -16.66) was estimated, and finally LDL-cholesterol had a WMD of -14.88 mg/dl (95% CI -36.27 to 6.51).ConclusionsLMWH showed to be at least as safe as UFH for ECC anticoagulation in chronic hemodialysis. The limited number of studies reporting on osteoporosis and HIT does not allow any conclusion for these outcomes. Larger studies are needed to evaluate properly the safety of LMWH in chronic hemodialysis.
| S-EPMC5463373 | biostudies-literature
Project description:Background:Low-molecular-weight-heparins (LMWHs) have been established for the treatment of cancer-associated venous thromboembolism (VTE). Recently published randomized controlled trials (RCTs) have compared direct oral anticoagulants (DOACs) with LMWHs. The aim of this systematic review and meta-analysis was to evaluate efficacy and safety of DOACs versus LMWHs and update the evidence for treatment of VTE in cancer. Methods:Biomedical databases were screened for RCTs evaluating DOACs for cancer-associated VTE. Primary efficacy and safety outcomes of this meta-analysis were recurrent VTE and major bleeding at 6 months. Secondary outcomes comprised clinically relevant nonmajor bleeding (CRNMB), major gastrointestinal (GI) and genitourinary bleeding, mortality, fatal bleeding/pulmonary embolism, and treatment discontinuation rate. We performed prespecified subgroup analyses. Pooled relative risk (RR) and 95% confidence intervals (CIs) were obtained by the Mantel-Haenszel method within a random-effect model. Results:We screened 759 articles and included 4 RCTs (n = 2894). DOACs significantly reduced recurrent VTEs compared to LMWHs (5.2% vs 8.2%; RR, 0.62 [95% CI, 0.43-0.91]), but were associated with a nonsignificant increase in major bleedings (4.3% vs 3.3%; RR, 1.31 [95% CI, 0.83-2.08]) and a significant increase in CRNMB (10.4% vs 6.4%; RR, 1.65 [95% CI, 1.19-2.28]). Mortality risks were comparable between groups (RR, 0.99 [95% CI, 0.83-1.18]). Preterm treatment discontinuation was less common with DOACs (RR, 0.88 [95% CI, 0.81-0.96]). Major bleeding was more frequent in patients with GI cancer treated with DOACs (RR, 2.30 [95% CI, 1.08-4.88]). Conclusion:In patients with cancer-associated VTE, DOACs are more effective in preventing recurrent VTE compared to LMWH. However, risk of bleeding is increased with DOACs, especially in patients with GI cancer.
| S-EPMC7292654 | biostudies-literature