Should we consider heparin prophylaxis in COVID-19 patients? a systematic review and meta-analysis.
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ABSTRACT:
SUBMITTER: Abdel-Maboud M
PROVIDER: S-EPMC7439245 | biostudies-literature | 2021 Apr
REPOSITORIES: biostudies-literature
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Should we consider heparin prophylaxis in COVID-19 patients? a systematic review and meta-analysis.
Abdel-Maboud Mohamed M Menshawy Amr A Elgebaly Ahmed A Bahbah Eshak I EI El Ashal Gehad G Negida Ahmed A
Journal of thrombosis and thrombolysis 20200820 3
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Project description:Heparin thromboprophylaxis is routinely administered during hospitalization for COVID-19. Because of the immune stimulation related to COVID-19, there is ongoing concern regarding a heightened incidence of heparin-induced thrombocytopenia (HIT). We performed a literature search using PubMed, EMBASE, Cochrane, and medRxiv database to identify studies that reported clinical and laboratory characteristics and/or the incidence of HIT in patients with COVID-19. The primary aim was to systematically review the clinical features and outcomes of patients with COVID-19 with confirmed HIT. The secondary objective was to perform a meta-analysis to estimate the incidence of HIT in hospitalized patients with COVID-19. A meta-analysis of 7 studies including 5849 patients revealed the pooled incidence of HIT in COVID-19 of 0.8% (95% confidence interval [CI], 0.2%-3.2%; I2 = 89%). The estimated incidences were 1.2% (95% CI, 0.3%-3.9%; I2 = 65%) vs 0.1% (95% CI, 0.0%-0.4%; I2 = 0%) in therapeutic vs prophylactic heparin subgroups, respectively. The pooled incidences of HIT were higher in critically ill patients with COVID-19 (2.2%; 95% CI, 0.6%-8.3%; I2 = 72.5%) compared with noncritically ill patients (0.1%; 95% CI, 0.0%-0.4%: I2 = 0%). There were 19 cases of confirmed HIT and 1 with autoimmune HIT for clinical and laboratory characterization. The median time from heparin initiation to HIT diagnosis was 13.5 days (interquartile range, 10.75-16.25 days). Twelve (63%) developed thromboembolism after heparin therapy. In conclusion, the incidence of HIT in patients with COVID-19 was comparable to patients without COVID-19, with higher incidences with therapeutic anticoagulation and in critically ill patients.
| S-EPMC8455241 | biostudies-literature
Project description:UpdatesThis is the second version (first update) of the living systematic review, replacing the previous version (available as a data supplement). When citing this paper please consider adding the version number and date of access for clarity.ObjectiveTo determine and compare the effects of drug prophylaxis on severe acute respiratory syndrome coronavirus virus 2 (SARS-CoV-2) infection and coronavirus disease 2019 (covid-19).DesignLiving systematic review and network meta-analysis (NMA).Data sourcesWorld Health Organization covid-19 database, a comprehensive multilingual source of global covid-19 literature to 4 March 2022.Study selectionRandomised trials in which people at risk of covid-19 were allocated to prophylaxis or no prophylaxis (standard care or placebo). Pairs of reviewers independently screened potentially eligible articles.MethodsAfter duplicate data abstraction, we conducted random-effects bayesian network meta-analysis. We assessed risk of bias of the included studies using a modification of the Cochrane risk of bias 2.0 tool and assessed the certainty of the evidence using the grading of recommendations assessment, development and evaluation (GRADE) approach.ResultsThe second iteration of this living NMA includes 32 randomised trials which enrolled 25 147 participants and addressed 21 different prophylactic drugs; adding 21 trials (66%), 18 162 participants (75%) and 16 (76%) prophylactic drugs. Of the 16 prophylactic drugs analysed, none provided convincing evidence of a reduction in the risk of laboratory confirmed SARS-CoV-2 infection. For admission to hospital and mortality outcomes, no prophylactic drug proved different than standard care or placebo. Hydroxychloroquine and vitamin C combined with zinc probably increase the risk of adverse effects leading to drug discontinuation—risk difference for hydroxychloroquine (RD) 6 more per 1000 (95% credible interval (CrI) 2 more to 10 more); for vitamin C combined with zinc, RD 69 more per 1000 (47 more to 90 more), moderate certainty evidence.ConclusionsMuch of the evidence remains very low certainty and we therefore anticipate future studies evaluating drugs for prophylaxis may change the results for SARS-CoV-2 infection, admission to hospital and mortality outcomes. Both hydroxychloroquine and vitamin C combined with zinc probably increase adverse effects.Systematic review registrationThis review was not registered. The protocol established a priori is included as a supplement.FundingThis study was supported by the Canadian Institutes of Health Research (grant CIHR-IRSC:0579001321).
| S-EPMC8073806 | biostudies-literature
Project description:Heparin-induced thrombocytopenia (HIT) occurs in approximately 3% of patients receiving heparinoids. About 30-75% of patients with type 2 of HIT develop thrombosis as a result of platelet activation. The most important clinical symptom is thrombocytopenia. Patients with severe COVID-19 are among those receiving heparinoids. This meta-analysis performed to picture the current knowledge and results of published studies in this field. Three search engines were searched and 575 papers were found. After evaluation, 37 articles were finally selected of which 13 studies were quantitatively analyzed. The pooled frequency rate of suspected cases with HIT in 13 studies with 11,241 patients was 1.7%. The frequency of HIT was 8.2% in the extracorporeal membrane oxygenation subgroup with 268 patients and 0.8% in the hospitalization subgroup with 10,887 patients. The coincidence of these two conditions may increase the risk of thrombosis. Of the 37 patients with COVID-19 and confirmed HIT, 30 patients (81%) were treated in the intensive care unit or had severe COVID-19. The most commonly used anticoagulants were UFH in 22 cases (59.4%). The median platelet count before treatment was 237 (176-290) x 103/µl and the median nadir platelet count was 52 (31-90.5) x 103/µl.
| S-EPMC10203678 | biostudies-literature
Project description:Ivermectin has received particular attention as a potential treatment for COVID-19. However, the evidence to support its clinical efficacy is controversial. We undertook a new systematic review of ivermectin for the treatment and prophylaxis of COVID-19, including new primary studies, outcomes other than mortality, and grading the quality of the available evidence following the Cochrane guidance for methodology. We searched electronic databases, repository databases, and clinical trial registries (up to June 2021). The measure of treatment effect was risk difference (RD) with 95% confidence intervals (CIs). The GRADE system was used to assess the certainty of the evidence. The review includes 11 RCTs (2436 participants). The certainty of the available evidence was quite low or very low due to risk of bias, inconsistency, and imprecision. When the analysis was limited to patients with baseline mild or moderate disease (8 reports, 1283 patients), there were no differences in mortality between ivermectin and control groups (low level of certainty); in patients with baseline severe diseases (3 reports, 304 patients), the use of ivermectin significantly decreased mortality compared to the controls (RD -0.17; 95% CIs, -0.24/-0.10; p = 0.00001; low level of certainty). In terms of disease progression (to severe pneumonia, admission to intensive care unit, and/or mechanical ventilation), the results were much the same. At day 14, the rate of patients with a negative RT-PCR test was 21% higher (from 5 to 36% higher) for ivermectin recipients than it was for the controls (low quality of evidence). Three studies (736 subjects) indicated that prophylaxis with ivermectin increased the likelihood of preventing COVID-19 compared to controls (low quality of evidence). Serious adverse events were rarely reported. There is limited evidence for the benefit of ivermectin for COVID-19 treatment and prophylaxis, and most of this evidence is of low quality. Further evidence is needed to fine-tune potential indications and optimal treatment protocols for ivermectin as a treatment for COVID-19.
| S-EPMC8470309 | biostudies-literature
Project description:BackgroundWhile the landscape of vaccine and treatment candidates against the novel coronavirus disease 2019 (COVID-19) has been reviewed systematically, prophylactic candidates remain unexplored.ObjectivesTo map pre- and postexposure prophylactic (PrEP and PEP) candidate for COVID-19.Data sourcesPubMed/Medline, Embase, International Committee of Medical Journal Editors and International Clinical Trials Registry Platform clinical trial registries and medRxiv.Study eligibility criteria and participantsAll studies in humans or animals and randomized controlled trials (RCTs) in humans reporting primary data on prophylactic candidates against COVID-19, excluding studies focused on key populations.InterventionsPrEP and PEP candidate for COVID-19.MethodsSystematic review and qualitative synthesis of COVID-19 PrEP and PEP studies and RCTs complemented by search of medRxiv and PubMed and Embase for studies reporting RCT outcomes since systematic review search completion.ResultsWe identified 13 studies (from 2119 database records) and 117 RCTs (from 5565 RCTs listed in the registries) that met the inclusion criteria. Non-RCT studies reported on cross-sectional studies using hydroxychloroquine (HCQ) in humans (n = 2) or reported on animal studies (n = 7), most of which used antibodies. All five completed RCTs focused on the use of HCQ as either PrEP or PEP, and these and the cross-sectional studies reported no prophylactic effect. The majority of ongoing RCTs evaluated HCQ or other existing candidates including non-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines, anti(retro)virals or use of vitamins and supplements.ConclusionsThe key message from completed studies and RCTs seems to be that HCQ does not work. There is little evidence regarding other compounds, with all RCTs using candidates other than HCQ still ongoing. It remains to be seen if the portfolio of existing molecules being evaluated in RCTs will identify successful prophylaxis against COVID-19 or if there is a need for the development of new candidates.
| S-EPMC7813508 | biostudies-literature
Project description:International guidelines recommend low-molecular-weight heparin (LMWH) as first-line pharmacological option for the prevention of venous thromboembolism (VTE) in many patient categories. Guidance on the optimal prophylactic dose is lacking. We conducted a systematic review with meta-analysis and trial sequential analysis (TSA) of randomized controlled trials to assess benefits and harms of low-dose LMWH versus placebo or no treatment for thrombosis prophylaxis in patients at risk of VTE. PubMed, Cochrane Library, Web of Science, and Embase were searched up to June 2019. Results were presented as relative risk (RR) with conventional and TSA-adjusted confidence intervals (CI). Forty-four trials with a total of 22,579 participants were included. Six (14%) had overall low risk of bias. Low-dose LMWH was not statistically significantly associated with all-cause mortality (RR 0.99; 95%CI 0.85-1.14; TSA-adjusted CI 0.89-1.16) but did reduce symptomatic VTE (RR 0.62; 95%CI 0.48-0.81; TSA-adjusted CI 0.44-0.89) and any VTE (RR 0.61; 95%CI 0.50-0.75; TSA-adjusted CI 0.49-0.82). Analyses on major bleeding (RR 1.07; 95%CI 0.72-1.59), as well as serious adverse events (SAE) and clinically relevant non-major bleeding were inconclusive. There was very low to moderate-quality evidence that low-dose LMWH for thrombosis prophylaxis did not decrease all-cause mortality but reduced the incidence of symptomatic and asymptomatic VTE, while the analysis of the effects on bleeding and adverse events remained inconclusive.
| S-EPMC6947554 | biostudies-literature
Project description:ObjectiveTo analyze the survival rates of patients with COVID-19 supported with extracorporeal membrane oxygenation (ECMO) and compare the survival rates of patients with COVID-19 supported with ECMO to patients with influenza supported with ECMO.DesignA systematic review and meta-analysis to assess the impact of ECMO as supportive therapy of COVID-19.SettingThe authors performed a search through the Cochrane, EMBASE, and MEDLINE/PubMed databases from inception to February 19, 2021, for studies reporting hospitalized patients with COVID-19 managed with ECMO.ParticipantsA total of 134 studies were selected, including 6 eligible for the comparative meta-analysis of COVID-19 versus influenza.InterventionsThe authors pooled the risk ratio and random effects model.Measurements and main resultsThe primary endpoint was the overall mortality of patients with COVID-19 receiving ECMO. Of the total number of 58,472 patients with COVID-19 reported, ECMO was used in 4,044 patients. The analysis suggested an overall in-hospital mortality of 39% (95% CI 0.34-0.43). In the comparative analysis, patients with COVID-19 on ECMO had a higher risk ratio (RR) for mortality when compared to influenza patients on ECMO: 72/164 (44%) v 71/186 (38%) RR 1.34; 95% CI 1.05-1.71; p = 0.03.ConclusionsECMO could be beneficial in patients with COVID-19, according to the authors' meta-analysis. The reported mortality rate was 39%. This systematic analysis can provide clinical advice in the current era and ongoing pandemic.
| S-EPMC8585556 | biostudies-literature
Project description:BackgroundTixagevimab/cilgavimab (Tix/Cil) shows promise as a prophylactic treatment against coronavirus disease 2019 (COVID-19) in solid organ transplant recipients (SOTRs). This study was performed to assess the effectiveness of Tix/Cil for preexposure prophylaxis against COVID-19 in this population.MethodsWe systematically searched the Cochrane Library, Web of Science, PubMed, and Embase databases to identify articles relevant to our study up to December 15, 2023. Comprehensive Meta-Analysis (ver. 3.0) was used for data analysis.ResultsThe meta-analysis included seven eligible retrospective studies, encompassing a total of 4,026 SOTRs. The analysis revealed significant differences in SOTRs who received Tix/Cil preexposure prophylaxis relative to those who did not. Specifically, these differences were observed in the incidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (odds ratio [OR], 0.30; 95% confidence interval [CI], 0.15-0.60), hospitalization (OR, 0.24; 95% CI, 0.08-0.70), and intensive care unit admission (OR, 0.07; 95% CI, 0.02-0.22). However, mortality rate did not differ significantly between the two groups (P=0.06).ConclusionsThe evidence supporting the effectiveness of Tix/Cil as preexposure prophylaxis against SARS-CoV-2 in SOTRs is of a low to moderate level. Further high-quality research is necessary to understand its effects on this population.
| S-EPMC11228381 | biostudies-literature
Project description:PurposeThe optimal amount of anticoagulation for critically ill COVID-19 patients is controversial. Therefore, we aimed to evaluate the efficacy and safety of escalated doses of anticoagulation in critically ill patients with severe COVID-19.Materials and methodsWe conducted a systematic search of three major databases, including PubMed, Cochrane Library, and Embase, from inception to May 2022. Randomized controlled trials (RCTs) were included comparing therapeutic or intermediate doses to standard prophylactic doses of anticoagulants in critically ill COVID-19 patients, with heparins as the only anticoagulation therapy considered.ResultsOut of the six RCTs, 2130 patients were administered escalated dose anticoagulation (50.2%) and standard thromboprophylaxis therapy (49.8%). The escalated dose showed no significant impact on mortality (RR, 1.01; 95% CI, 0.90-1.13). Although there was no significant difference in DVT (RR, 0.81; 95% CI, 0.61-1.08), the risk of PE was significantly reduced in patients receiving escalated dose anticoagulation (RR, 0.35; 95% CI, 0.21-0.60), with an increased risk of bleeding events (RR, 1.65; 95% CI, 1.08-2.53).ConclusionThis systematic review and meta-analysis fail to support escalated anticoagulation doses to reduce mortality in critically ill COVID-19 patients. However, higher doses of anticoagulants appear to reduce thrombotic events while increasing the risk of bleeding effectively.
| S-EPMC10211463 | biostudies-literature
Project description:BackgroundDuring the COVID-19 pandemic, some populations, including immunocompromised patients, could not tolerate COVID-19 vaccination or had low responses. Evusheld is a combined neutralizing monoclonal antibody containing tixagevimab and cilgavimab. The World Health Organization (WHO) has approved this combination as pre-exposure prophylaxis (PrEP) and treatment for immunocompromised patients. With the new variant, the (WHO) recommended an increase in dose from 300 to 600 mg with a booster dose after 6 months. The target of this review was to compare the efficacy of the two doses, 300 mg and 600 mg of tixagevimab/cilgavimab (Evusheld) as prophylaxis for higher-risk individuals to reveal if there is a significant difference in efficacy between those two doses of the drug.MethodsIn this study, electronic databases (PubMed, Web of Science core collection, Scopus, and Cochran) were investigated for articles up to 31/12/2022 in English using a well-established search strategy. We included studies conducted in immunocompromised patients (aged ≥ 12 years) (WHO) received Evusheld as prophylaxis or treatment for COVID-19. After excluding studies inconsistent with the selection criteria, 24 were involved, 22 of which were included in the meta-analysis. We analyzed the data by using RevMan 5.4 program software.ResultsIn the double-arm subgroup analysis, Evusheld 600 mg, administered as prophylaxis, showed no significant difference in the COVID-19 infection rate, mortality rate, or needed hospitalization rate compared with the dose of 300 mg (p = 0.13, p = 0.29, and p = 0.25, respectively). In the single-arm subgroup analysis, Evusheld 600 mg, administered as prophylaxis, showed a significant decrease in the COVID-19 infection rate and the hospitalization rate compared with the dose of 300 mg (p = 0.0001, p = 0.007, respectively). As a treatment, Evusheld showed a significant decrease in the mortality rate over the placebo group (p = 0.01) in COVID-19 patients.ConclusionThis result indicated that Evusheld was an effective prophylactic and therapeutic drug for COVID-19 infection, especially for immunocompromised patients, but there was no considerable variation between the high and low doses. Further prospective and randomized controlled trials (RCTs) with increased population sizes are necessary to show the valuable benefit of the high dose of Evusheld in COVID-19 prevention and treatment and to compare the difference between the two doses within adverse events.
| S-EPMC10768288 | biostudies-literature