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The Cochrane Database of Systematic... Mar 2022The primary manifestation of coronavirus disease 2019 (COVID-19) is respiratory insufficiency that can also be related to diffuse pulmonary microthrombosis and... (Review)
Review
BACKGROUND
The primary manifestation of coronavirus disease 2019 (COVID-19) is respiratory insufficiency that can also be related to diffuse pulmonary microthrombosis and thromboembolic events, such as pulmonary embolism, deep vein thrombosis, or arterial thrombosis. People with COVID-19 who develop thromboembolism have a worse prognosis. Anticoagulants such as heparinoids (heparins or pentasaccharides), vitamin K antagonists and direct anticoagulants are used for the prevention and treatment of venous or arterial thromboembolism. Besides their anticoagulant properties, heparinoids have an additional anti-inflammatory potential. However, the benefit of anticoagulants for people with COVID-19 is still under debate.
OBJECTIVES
To assess the benefits and harms of anticoagulants versus active comparator, placebo or no intervention in people hospitalised with COVID-19.
SEARCH METHODS
We searched the CENTRAL, MEDLINE, Embase, LILACS and IBECS databases, the Cochrane COVID-19 Study Register and medRxiv preprint database from their inception to 14 April 2021. We also checked the reference lists of any relevant systematic reviews identified, and contacted specialists in the field for additional references to trials.
SELECTION CRITERIA
Eligible studies were randomised controlled trials (RCTs), quasi-RCTs, cluster-RCTs and cohort studies that compared prophylactic anticoagulants versus active comparator, placebo or no intervention for the management of people hospitalised with COVID-19. We excluded studies without a comparator group and with a retrospective design (all previously included studies) as we were able to include better study designs. Primary outcomes were all-cause mortality and necessity for additional respiratory support. Secondary outcomes were mortality related to COVID-19, deep vein thrombosis, pulmonary embolism, major bleeding, adverse events, length of hospital stay and quality of life.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methodological procedures. We used Cochrane RoB 1 to assess the risk of bias for RCTs, ROBINS-I to assess risk of bias for non-randomised studies (NRS) and GRADE to assess the certainty of evidence. We meta-analysed data when appropriate.
MAIN RESULTS
We included seven studies (16,185 participants) with participants hospitalised with COVID-19, in either intensive care units, hospital wards or emergency departments. Studies were from Brazil (2), Iran (1), Italy (1), and the USA (1), and two involved more than country. The mean age of participants was 55 to 68 years and the follow-up period ranged from 15 to 90 days. The studies assessed the effects of heparinoids, direct anticoagulants or vitamin K antagonists, and reported sparse data or did not report some of our outcomes of interest: necessity for additional respiratory support, mortality related to COVID-19, and quality of life. Higher-dose versus lower-dose anticoagulants (4 RCTs, 4647 participants) Higher-dose anticoagulants result in little or no difference in all-cause mortality (risk ratio (RR) 1.03, 95% CI 0.92 to 1.16, 4489 participants; 4 RCTs) and increase minor bleeding (RR 3.28, 95% CI 1.75 to 6.14, 1196 participants; 3 RCTs) compared to lower-dose anticoagulants up to 30 days (high-certainty evidence). Higher-dose anticoagulants probably reduce pulmonary embolism (RR 0.46, 95% CI 0.31 to 0.70, 4360 participants; 4 RCTs), and slightly increase major bleeding (RR 1.78, 95% CI 1.13 to 2.80, 4400 participants; 4 RCTs) compared to lower-dose anticoagulants up to 30 days (moderate-certainty evidence). Higher-dose anticoagulants may result in little or no difference in deep vein thrombosis (RR 1.08, 95% CI 0.57 to 2.03, 3422 participants; 4 RCTs), stroke (RR 0.91, 95% CI 0.40 to 2.03, 4349 participants; 3 RCTs), major adverse limb events (RR 0.33, 95% CI 0.01 to 7.99, 1176 participants; 2 RCTs), myocardial infarction (RR 0.86, 95% CI 0.48 to 1.55, 4349 participants; 3 RCTs), atrial fibrillation (RR 0.35, 95% CI 0.07 to 1.70, 562 participants; 1 study), or thrombocytopenia (RR 0.94, 95% CI 0.71 to 1.24, 2789 participants; 2 RCTs) compared to lower-dose anticoagulants up to 30 days (low-certainty evidence). It is unclear whether higher-dose anticoagulants have any effect on necessity for additional respiratory support, mortality related to COVID-19, and quality of life (very low-certainty evidence or no data). Anticoagulants versus no treatment (3 prospective NRS, 11,538 participants) Anticoagulants may reduce all-cause mortality but the evidence is very uncertain due to two study results being at critical and serious risk of bias (RR 0.64, 95% CI 0.55 to 0.74, 8395 participants; 3 NRS; very low-certainty evidence). It is uncertain if anticoagulants have any effect on necessity for additional respiratory support, mortality related to COVID-19, deep vein thrombosis, pulmonary embolism, major bleeding, stroke, myocardial infarction and quality of life (very low-certainty evidence or no data). Ongoing studies We found 62 ongoing studies in hospital settings (60 RCTs, 35,470 participants; 2 prospective NRS, 120 participants) in 20 different countries. Thirty-five ongoing studies plan to report mortality and 26 plan to report necessity for additional respiratory support. We expect 58 studies to be completed in December 2021, and four in July 2022. From 60 RCTs, 28 are comparing different doses of anticoagulants, 24 are comparing anticoagulants versus no anticoagulants, seven are comparing different types of anticoagulants, and one did not report detail of the comparator group.
AUTHORS' CONCLUSIONS
When compared to a lower-dose regimen, higher-dose anticoagulants result in little to no difference in all-cause mortality and increase minor bleeding in people hospitalised with COVID-19 up to 30 days. Higher-dose anticoagulants possibly reduce pulmonary embolism, slightly increase major bleeding, may result in little to no difference in hospitalisation time, and may result in little to no difference in deep vein thrombosis, stroke, major adverse limb events, myocardial infarction, atrial fibrillation, or thrombocytopenia. Compared with no treatment, anticoagulants may reduce all-cause mortality but the evidence comes from non-randomised studies and is very uncertain. It is unclear whether anticoagulants have any effect on the remaining outcomes compared to no anticoagulants (very low-certainty evidence or no data). Although we are very confident that new RCTs will not change the effects of different doses of anticoagulants on mortality and minor bleeding, high-quality RCTs are still needed, mainly for the other primary outcome (necessity for additional respiratory support), the comparison with no anticoagulation, when comparing the types of anticoagulants and giving anticoagulants for a prolonged period of time.
Topics: Aged; Anticoagulants; COVID-19; Heparin; Humans; Middle Aged; SARS-CoV-2; Thromboembolism
PubMed: 35244208
DOI: 10.1002/14651858.CD013739.pub2 -
The Cochrane Database of Systematic... Aug 2023The coronavirus disease 2019 (COVID-19) pandemic has impacted healthcare systems worldwide. Multiple reports on thromboembolic complications related to COVID-19 have... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The coronavirus disease 2019 (COVID-19) pandemic has impacted healthcare systems worldwide. Multiple reports on thromboembolic complications related to COVID-19 have been published, and researchers have described that people with COVID-19 are at high risk for developing venous thromboembolism (VTE). Anticoagulants have been used as pharmacological interventions to prevent arterial and venous thrombosis, and their use in the outpatient setting could potentially reduce the prevalence of vascular thrombosis and associated mortality in people with COVID-19. However, even lower doses used for a prophylactic purpose may result in adverse events such as bleeding. It is important to consider the evidence for anticoagulant use in non-hospitalised people with COVID-19.
OBJECTIVES
To evaluate the benefits and harms of prophylactic anticoagulants versus active comparators, placebo or no intervention, or non-pharmacological interventions in non-hospitalised people with COVID-19.
SEARCH METHODS
We used standard, extensive Cochrane search methods. The latest search date was 18 April 2022.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) comparing prophylactic anticoagulants with placebo or no treatment, another active comparator, or non-pharmacological interventions in non-hospitalised people with COVID-19. We included studies that compared anticoagulants with a different dose of the same anticoagulant. We excluded studies with a duration of under two weeks.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methodological procedures. Our primary outcomes were all-cause mortality, VTE (deep vein thrombosis (DVT) or pulmonary embolism (PE)), and major bleeding. Our secondary outcomes were DVT, PE, need for hospitalisation, minor bleeding, adverse events, and quality of life. We used GRADE to assess the certainty of the evidence.
MAIN RESULTS
We included five RCTs with up to 90 days of follow-up (short term). Data were available for meta-analysis from 1777 participants. Anticoagulant compared to placebo or no treatment Five studies compared anticoagulants with placebo or no treatment and provided data for three of our outcomes of interest (all-cause mortality, major bleeding, and adverse events). The evidence suggests that prophylactic anticoagulants may lead to little or no difference in all-cause mortality (risk ratio (RR) 0.36, 95% confidence interval (CI) 0.04 to 3.61; 5 studies; 1777 participants; low-certainty evidence) and probably reduce VTE from 3% in the placebo group to 1% in the anticoagulant group (RR 0.36, 95% CI 0.16 to 0.85; 4 studies; 1259 participants; number needed to treat for an additional beneficial outcome (NNTB) = 50; moderate-certainty evidence). There may be little to no difference in major bleeding (RR 0.36, 95% CI 0.01 to 8.78; 5 studies; 1777 participants; low-certainty evidence). Anticoagulants probably result in little or no difference in DVT (RR 1.02, 95% CI 0.30 to 3.46; 3 studies; 1009 participants; moderate-certainty evidence), but probably reduce the risk of PE from 2.7% in the placebo group to 0.7% in the anticoagulant group (RR 0.25, 95% CI 0.08 to 0.79; 3 studies; 1009 participants; NNTB 50; moderate-certainty evidence). Anticoagulants probably lead to little or no difference in reducing hospitalisation (RR 1.01, 95% CI 0.59 to 1.75; 4 studies; 1459 participants; moderate-certainty evidence) and may lead to little or no difference in adverse events (minor bleeding, RR 2.46, 95% CI 0.90 to 6.72; 5 studies, 1777 participants; low-certainty evidence). Anticoagulant compared to a different dose of the same anticoagulant One study compared anticoagulant (higher-dose apixaban) with a different (standard) dose of the same anticoagulant and reported five relevant outcomes. No cases of all-cause mortality, VTE, or major bleeding occurred in either group during the 45-day follow-up (moderate-certainty evidence). Higher-dose apixaban compared to standard-dose apixaban may lead to little or no difference in reducing the need for hospitalisation (RR 1.89, 95% CI 0.17 to 20.58; 1 study; 278 participants; low-certainty evidence) or in the number of adverse events (minor bleeding, RR 0.47, 95% CI 0.09 to 2.54; 1 study; 278 participants; low-certainty evidence). Anticoagulant compared to antiplatelet agent One study compared anticoagulant (apixaban) with antiplatelet agent (aspirin) and reported five relevant outcomes. No cases of all-cause mortality or major bleeding occurred during the 45-day follow-up (moderate-certainty evidence). Apixaban may lead to little or no difference in VTE (RR 0.36, 95% CI 0.01 to 8.65; 1 study; 279 participants; low-certainty evidence), need for hospitalisation (RR 3.20, 95% CI 0.13 to 77.85; 1 study; 279 participants; low-certainty evidence), or adverse events (minor bleeding, RR 2.13, 95% CI 0.40 to 11.46; 1 study; 279 participants; low-certainty evidence). No included studies reported on quality of life or investigated anticoagulants compared to a different anticoagulant, or anticoagulants compared to non-pharmacological interventions.
AUTHORS' CONCLUSIONS
We found low- to moderate-certainty evidence from five RCTs that prophylactic anticoagulants result in little or no difference in major bleeding, DVT, need for hospitalisation, or adverse events when compared with placebo or no treatment in non-hospitalised people with COVID-19. Low-certainty evidence indicates that prophylactic anticoagulants may result in little or no difference in all-cause mortality when compared with placebo or no treatment, but moderate-certainty evidence indicates that prophylactic anticoagulants probably reduce the incidence of VTE and PE. Low-certainty evidence suggests that comparing different doses of the same prophylactic anticoagulant may result in little or no difference in need for hospitalisation or adverse events. Prophylactic anticoagulants may result in little or no difference in risk of VTE, hospitalisation, or adverse events when compared with antiplatelet agents (low-certainty evidence). Given that there were only short-term data from one study, these results should be interpreted with caution. Additional trials of sufficient duration are needed to clearly determine any effect on clinical outcomes.
Topics: Humans; Anticoagulants; Platelet Aggregation Inhibitors; COVID-19; Venous Thromboembolism; Aspirin; Pulmonary Embolism
PubMed: 37591523
DOI: 10.1002/14651858.CD015102.pub2 -
Medicina (Kaunas, Lithuania) Aug 2023: Severe acute respiratory syndrome coronavirus 2 caused the coronavirus disease of 2019 (COVID-19), which rapidly became a pandemic, claiming millions of lives. Apart... (Meta-Analysis)
Meta-Analysis Review
: Severe acute respiratory syndrome coronavirus 2 caused the coronavirus disease of 2019 (COVID-19), which rapidly became a pandemic, claiming millions of lives. Apart from the main manifestations of this infection concerning the respiratory tract, such as pneumonia, there are also many manifestations from the gastrointestinal tract. Of these, bleeding from the gastrointestinal tract is a significant complication quite dangerous for life. This bleeding is divided into upper and lower, and the primary pathophysiological mechanism is the entering of the virus into the host cells through the Angiotensin-converting enzyme 2 receptors. Also, other comorbidities and the medication of corticosteroids and anticoagulants are considered to favor the occurrence of gastrointestinal bleeding (GIB). : This systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, and the studies were searched in two different databases (Scopus and PubMed) from November 2019 until February 2023. All studies that reported GIB events among COVID-19 patients were included. : 33 studies were selected and reviewed to estimate the prevalence of GIB. A total of 134,905 patients with COVID-19 were included in these studies, and there were 1458 episodes of GIB. The prevalence of GIB, in these 33 studies, ranges from 0.47% to 19%. This range of prevalence is justified by the characteristics of the COVID-19 patients. These characteristics are the severity of COVID-19, anticoagulant and other drug treatments, the selection of only patients with gastrointestinal manifestations, etc. The pooled prevalence of gastrointestinal bleeding was estimated to be 3.05%, rising to 6.2% when only anticoagulant patients were included. : GIB in COVID-19 patients is not a rare finding, and its appropriate and immediate treatment is necessary as it can be life-threatening. The most common clinical findings are melena and hematemesis, which characterize upper GIB. Treatment can be conservative; however, endoscopic management of bleeding with embolization is deemed necessary in some cases.
Topics: Humans; COVID-19; Prevalence; Gastrointestinal Hemorrhage; Anticoagulants
PubMed: 37629790
DOI: 10.3390/medicina59081500 -
The Cochrane Database of Systematic... Oct 2020Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by arterial or venous thrombosis (or both), and/or pregnancy morbidity in association with... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by arterial or venous thrombosis (or both), and/or pregnancy morbidity in association with the presence of antiphospholipid antibodies. The prevalence of APS is estimated at 40 to 50 cases per 100,000 people. The most common sites of thrombosis are cerebral arteries and deep veins of the lower limbs. People with a definite APS diagnosis have an increased lifetime risk of recurrent thrombotic events.
OBJECTIVES
To assess the effects of antiplatelet (AP) or anticoagulant agents, or both, for the secondary prevention of recurrent thrombosis, particularly ischemic stroke, in people with APS.
SEARCH METHODS
We last searched the MEDLINE, Embase, CENTRAL, Cochrane Stroke Group Trials Register, and ongoing trials registers on 22 November 2019. We checked reference lists of included studies, systematic reviews, and practice guidelines. We also contacted experts in the field.
SELECTION CRITERIA
We included randomized controlled trials (RCTs) that evaluated any anticoagulant or AP agent, or both, in the secondary prevention of thrombosis in people with APS, according to the criteria valid when the study took place. We did not include studies specifically addressing women with obstetrical APS.
DATA COLLECTION AND ANALYSIS
Pairs of review authors independently worked on each step of the review, following Cochrane methods. We summarized the evidence using the GRADE approach.
MAIN RESULTS
We identified eight studies including 811 participants that compared different AP or anticoagulant agents. NOAC (non-VKA oral anticoagulant: rivaroxaban 15 or 20 mg/d) versus standard-dose VKA (vitamin K antagonist: warfarin at moderate International Normalized Ratio [INR] - 2.5) or adjusted [INR 2.0-3.0] dose): In three studies there were no differences in any thromboembolic event (including death) and major bleeding (moderate-certainty evidence), but an increased risk of stroke (risk ratio [RR] 14.13, 95% confidence interval [CI] 1.87 to 106.8; moderate-certainty evidence). One of the studies reported a small benefit of rivaroxaban in terms of quality of life at 180 days measured as health state on Visual Analogue Scale (mean difference [MD] 7 mm, 95% CI 2.01 to 11.99; low-certainty evidence), but not measured as health utility on a scale from 0 to 1 (MD 0.04, 95% CI -0.02 to 0.10; low-certainty evidence). High-dose VKA (warfarin with a target INR of 3.1 to 4.0 [mean 3.3] or 3.5 [mean 3.2]) versus standard-dose VKA (warfarin with a target INR of 2.0 to 3.0 [mean 2.3] or 2.5 [mean 2.5]): In two studies there were no differences in the rates of thrombotic events and major bleeding (RR 2.22, 95% CI 0.79 to 6.23, low-certainty evidence), but an increased risk of minor bleeding in one study during a mean of 3.4 years (standard deviation [SD] 1.2) of follow-up (RR 2.55, 95% CI 1.07 to 6.07). In both trials there was evidence of a higher risk of any bleeding (hazard ratio [HR] 2.03 95% CI 1.12 to 3.68; low-certainty evidence) in the high-dose VKA group, and for this outcome (any bleeding) the incidence is not different, only the time to event is showing an effect. Standard-dose VKA plus a single AP agent (warfarin at a target INR of 2.0 to 3.0 plus aspirin 100 mg/d) versus standard-dose VKA (warfarin at a target INR of 2.0 to 3.0): One high-risk-of-bias study showed an increased risk of any thromboembolic event with combined treatment (RR 2.14, 95% CI 1.04 to 4.43; low-certainty evidence) and reported on major bleeding with five cases in the combined treatment group and one case in the standard-dose VKA treatment group, resulting in RR 7.42 (95% CI 0.91 to 60.7; low-certainty evidence) and no differences for secondary outcomes (very low- to low-certainty evidence). Single/dual AP agent and standard-dose VKA (pooled results): Two high-risk-of-bias studies compared a combination of AP and VKA (aspirin 100 mg/d plus warfarin or unspecified VKA at a target INR of 2.0 to 3.0 or 2.0 to 2.5) with a single AP agent (aspirin 100 mg/d), but did not provide any conclusive evidence regarding the effects of those drugs in people with APS (very low-certainty evidence). One of the above-mentioned studies was a three-armed study that compared a combination of AP and VKA (aspirin 100 mg/d plus warfarin at a target INR of 2.0 to 2.5) with dual AP therapy (aspirin 100 mg/d plus cilostazol 200 mg/d) and dual AP therapy (aspirin 100 mg/d plus cilostazol 200 mg/d) versus a single AP treatment (aspirin 100 mg/d). This study reported on stroke (very low-certainty evidence) but did not report on any thromboembolic events, major bleeding, or any secondary outcomes. We identified two ongoing studies and three studies are awaiting classification.
AUTHORS' CONCLUSIONS
The evidence identified indicates that NOACs compared with standard-dose VKAs may increase the risk of stroke and do not appear to alter the risk of other outcomes (moderate-certainty evidence). Using high-dose VKA versus standard-dose VKA did not alter the risk of any thromboembolic event or major bleeding but may increase the risk of any form of bleeding (low-certainty evidence). Standard-dose VKA combined with an AP agent compared with standard-dose VKA alone may increase the risk of any thromboembolic event and does not appear to alter the risk of major bleeding or other outcomes (low-certainty evidence). The evidence is very uncertain about the benefit or harm of using standard-dose VKA plus AP agents versus single or dual AP therapy, or dual versus single AP therapy, for the secondary prevention of recurrent thrombosis in people with APS (very low-certainty evidence).
Topics: Anticoagulants; Antiphospholipid Syndrome; Cause of Death; Factor Xa Inhibitors; Hemorrhage; Humans; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Rivaroxaban; Secondary Prevention; Stroke; Thromboembolism; Warfarin
PubMed: 33045766
DOI: 10.1002/14651858.CD012169.pub3 -
Journal of Critical Care Oct 2023The initiation of the extracorporeal membrane oxygenation (ECMO) is associated with complex coagulatory and inflammatory processes and consequently needed... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
The initiation of the extracorporeal membrane oxygenation (ECMO) is associated with complex coagulatory and inflammatory processes and consequently needed anticoagulation. Systemic anticoagulation bears an additional risk of serious bleeding, and its monitoring is of immense importance. Therefore, our work aims to analyze the association of anticoagulation monitoring with bleeding during ECMO support.
MATERIAL AND METHODS
Systematic literature review and meta-analysis, complying with the PRISMA guidelines (PROSPERO-CRD42022359465).
RESULTS
Seventeen studies comprising 3249 patients were included in the final analysis. Patients experiencing hemorrhage had a longer activated partial thromboplastin time (aPTT), a longer ECMO duration, and higher mortality. We could not find strong evidence of any aPTT threshold association with the bleeding occurrence, as less than half of authors reported a potential relationship. Finally, we identified the acute kidney injury (66%, 233/356) and hemorrhage (46%, 469/1046) to be the most frequent adverse events, while almost one-half of patients did not survive to discharge (47%, 1192/2490).
CONCLUSION
The aPTT-guided anticoagulation is still the standard of care in ECMO patients. We did not find strong evidence supporting the aPTT-guided monitoring during ECMO. Based on the weight of the available evidence, further randomized trials are crucial to clarify the best monitoring strategy.
Topics: Humans; Partial Thromboplastin Time; Anticoagulants; Extracorporeal Membrane Oxygenation; Retrospective Studies; Hemorrhage; Heparin
PubMed: 37244207
DOI: 10.1016/j.jcrc.2023.154332 -
Annals of Vascular Surgery Mar 2022PAD is a significant cause of morbidity and mortality affecting over 200 million people worldwide. Current guidelines recommend at least a single antiplatelet or... (Meta-Analysis)
Meta-Analysis
BACKGROUND
PAD is a significant cause of morbidity and mortality affecting over 200 million people worldwide. Current guidelines recommend at least a single antiplatelet or anticoagulant agent in symptomatic PAD and lifelong antithrombotic treatment after a revascularization procedure. The aim of this systematic review and meta-analysis was to investigate the efficacy and safety of direct oral anticoagulants (DOACs) in patients with peripheral artery disease (PAD). PAD is a significant cause of morbidity and mortality affecting over 200 million people worldwide.
METHODS
The present systematic review and meta-analysis was performed according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. Risk ratios (RR) were calculated using the random effects model.
RESULTS
Overall, 10 studies were included in this systematic review and meta-analysis. In 4 studies, 14,257 patients with PAD were enrolled and they were assigned to receive either aspirin (ASA)+/- clopidogrel (N = 5,894) or DOAC+/- anti-platelet (e.g., ASA, clopidogrel) (n = 8,363). Non DOAC users were found to have higher reintervention rates (RR 1.12; 95% CI 1.01-1.24; P = 0.025) compared to DOAC users. No statistically significant difference was observed between the 2 groups, in terms of major bleeding (RR 0.78; 95% CI 0.50-1.23; P = 0.285), all-cause mortality (RR 0.98; 95% CI: 0.83-1.16; P = 0.818) and cardiovascular mortality (RR: 0.99; 95% CI: 0.73-1.333; P = 0.946) mortality. In addition, two real-world studies comparing DOAC with warfarin showed decreased rates of major cardiovascular events in the DOAC group.
CONCLUSION
DOAC use alone or combined with an anti-platelet agent could be associated with lower re-intervention rates, without increasing the risk for adverse bleeding events. However, this study failed to detect any difference in terms of all-cause mortality, MACEs and MALEs between DOAC users and DOAC naïve patients. Future studies are needed to better determine the efficacy and safety of DOACs in patients with PAD.
Topics: Administration, Oral; Anticoagulants; Humans; Peripheral Arterial Disease; Platelet Aggregation Inhibitors
PubMed: 34644644
DOI: 10.1016/j.avsg.2021.07.028 -
Journal of Medical Internet Research Jul 2023Oral anticoagulation is the cornerstone treatment of several diseases. Its management is often challenging, and different telemedicine strategies have been implemented... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Oral anticoagulation is the cornerstone treatment of several diseases. Its management is often challenging, and different telemedicine strategies have been implemented to support it.
OBJECTIVE
The aim of the study is to systematically review the evidence on the impact of telemedicine-based oral anticoagulation management compared to usual care on thromboembolic and bleeding events.
METHODS
Randomized controlled trials were searched in 5 databases from inception to September 2021. Two independent reviewers performed study selection and data extraction. Total thromboembolic events, major bleeding, mortality, and time in therapeutic range were assessed. Results were pooled using random effect models.
RESULTS
In total, 25 randomized controlled trials were included (n=25,746 patients) and classified as moderate to high risk of bias by the Cochrane tool. Telemedicine resulted in lower rates of thromboembolic events, though not statistically significant (n=13 studies, relative risk [RR] 0.75, 95% CI 0.53-1.07; I=42%), comparable rates of major bleeding (n=11 studies, RR 0.94, 95% CI 0.82-1.07; I=0%) and mortality (n=12 studies, RR 0.96, 95% CI 0.78-1.20; I=11%), and an improved time in therapeutic range (n=16 studies, mean difference 3.38, 95% CI 1.12-5.65; I=90%). In the subgroup of the multitasking intervention, telemedicine resulted in an important reduction of thromboembolic events (RR 0.20, 95% CI 0.08-0.48).
CONCLUSIONS
Telemedicine-based oral anticoagulation management resulted in similar rates of major bleeding and mortality, a trend for fewer thromboembolic events, and better anticoagulation quality compared to standard care. Given the potential benefits of telemedicine-based care, such as greater access to remote populations or people with ambulatory restrictions, these findings may encourage further implementation of eHealth strategies for anticoagulation management, particularly as part of multifaceted interventions for integrated care of chronic diseases. Meanwhile, researchers should develop higher-quality evidence focusing on hard clinical outcomes, cost-effectiveness, and quality of life.
TRIAL REGISTRATION
PROSPERO International Prospective Register of Systematic Reviews CRD42020159208; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=159208.
Topics: Humans; Anticoagulants; Quality of Life; Hemorrhage; Thromboembolism; Telemedicine
PubMed: 37428532
DOI: 10.2196/45922 -
Journal of Thrombosis and Haemostasis :... Mar 2022Data on anticoagulant treatment for upper extremity deep vein thrombosis (UEDVT) are largely derived from studies on usual site venous thromboembolism (VTE). (Meta-Analysis)
Meta-Analysis
BACKGROUND
Data on anticoagulant treatment for upper extremity deep vein thrombosis (UEDVT) are largely derived from studies on usual site venous thromboembolism (VTE).
OBJECTIVES
The objective of this meta-analysis was to evaluate the efficacy and safety of anticoagulant therapy for UEDVT.
PATIENTS/METHODS
A systematic search of MEDLINE and EMBASE was conducted for studies including patients with UEDVT. Primary outcomes were recurrent VTE and major bleeding. Secondary outcomes included clinically-relevant non-major bleeding and all-cause mortality. Summary estimates with 95% confidence intervals (CIs) were calculated by random-effect meta-analysis.
RESULTS
A total of 1473 patients from 11 prospective and nine retrospective studies were included. Sixty percent of patients had an indwelling catheter and 56.1% had cancer. Anticoagulant treatment consisted of direct oral anticoagulants, low molecular weight heparin followed by vitamin K antagonists, and low molecular weight heparin alone in 45.1%, 35.0%, and 19.9% of patients, respectively. During a median follow-up of 13 months, recurrent VTE occurred in 3% of patients (95% CI: 2-4; 21/1334 patients), major bleeding in 3% (95% CI: 2%-5%; 29/1235 patients), clinically-relevant non-major bleeding in 4% (95% CI: 3-6; 40/1075 patients), and all-cause mortality in 9% (95% CI: 5-15; 108/1084 patients). Rates of these outcomes were not significantly different between patients with or without cancer, patients with or without an indwelling catheter, and among those receiving different anticoagulant treatments.
CONCLUSIONS
In patients with UEDVT, anticoagulant treatment is associated with a low risk of recurrent VTE and a nonnegligible risk of major bleeding.
Topics: Anticoagulants; Heparin, Low-Molecular-Weight; Humans; Prospective Studies; Retrospective Studies; Upper Extremity Deep Vein Thrombosis; Venous Thromboembolism
PubMed: 34846783
DOI: 10.1111/jth.15614 -
The Cochrane Database of Systematic... Jan 2023Acute non-arteritic central retinal artery occlusion (CRAO) occurs as a sudden interruption of the blood supply to the retina and typically results in severe loss of... (Review)
Review
BACKGROUND
Acute non-arteritic central retinal artery occlusion (CRAO) occurs as a sudden interruption of the blood supply to the retina and typically results in severe loss of vision in the affected eye. Although many therapeutic interventions have been proposed, there is no generally agreed upon treatment regimen.
OBJECTIVES
To assess the effects of treatments for acute non-arteritic CRAO.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2022, Issue 2); Ovid MEDLINE; Embase.com; PubMed; Latin American and Caribbean Health Sciences Literature Database (LILACS); ClinicalTrials.gov; and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). We did not use any date or language restrictions in the electronic search for trials. We last searched the electronic databases on 15 February 2022.
SELECTION CRITERIA
We included randomized controlled trials (RCTs) comparing any interventions with another treatment in participants with acute non-arteritic CRAO in one or both eyes. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodology and graded the certainty of the body of evidence for primary (mean change in best-corrected visual acuity [BCVA]) and secondary (quality of life and adverse events) outcomes using the GRADE classification.
MAIN RESULTS
We included six RCTs with 223 total participants with acute non-arteritic CRAO; the studies ranged in size from 10 to 84 participants. The included studies varied geographically: one in Australia, one in Austria and Germany, two in China, one in Germany, and one in Italy. We were unable to conduct any meta-analyses due to study heterogeneity. None of the included studies compared the same pair of interventions: 1) tissue plasminogen activator (t-PA) versus intravenous saline; 2) t-PA versus isovolemic hemodilution, eyeball massage, intraocular pressure reduction, and anticoagulation; 3) nitroglycerin, methazolamide, mecobalamin tablets, vitamin B and B injections, puerarin and compound anisodine (also known as 654-2) along with oxygen inhalation, eyeball massage, tube expansion, and anticoagulation compared with and without intravenous recombinant tissue plasminogen activator (rt-PA); 4) transcorneal electrical stimulation (TES) with 0 mA versus with 66% of the participant's individual electrical phosphene threshold (EPT) at 20 Hz (66%) versus with 150% of the participant's individual EPT (150%) at 20 Hz; 5) ophthalmic artery branch retrograde thrombolysis versus superselective ophthalmic artery thrombolysis; and 6) pentoxifylline versus placebo. There was no evidence of an important difference in visual acuity between participants treated with t-PA versus intravenous saline (mean difference [MD] at 1 month -0.15 logMAR, 95% confidence interval [CI] -0.48 to 0.18; 1 study, 16 participants; low certainty evidence); t-PA versus isovolemic hemodilution, eyeball massage, intraocular pressure reduction, and anticoagulation (MD at 1 month -0.00 logMAR, 95% CI -0.24 to 0.23; 1 study, 82 participants; low certainty evidence); and TES with 0 mA versus TES with 66% of EPT at 20 Hz versus TES with 150% of EPT at 20 Hz. Participants treated with t-PA experienced higher rates of serious adverse effects. The other three comparisons did not report statistically significant differences. Other studies reported no data on secondary outcomes (quality of life or adverse events). AUTHORS' CONCLUSIONS: The current research suggests that proposed interventions for acute non-arteritic CRAO may not be better than observation or treatments of any kind such as eyeball massage, oxygen inhalation, tube expansion, and anticoagulation, but the evidence is uncertain. Large, well-designed RCTs are necessary to determine the most effective treatment for acute non-arteritic CRAO.
Topics: Humans; Tissue Plasminogen Activator; Retinal Artery Occlusion; Anticoagulants; China
PubMed: 36715340
DOI: 10.1002/14651858.CD001989.pub3 -
Annals of Vascular Surgery Apr 2021Ascending aortic thrombus (AAT) in a nonaneurysmal aorta is an extremely rare event and has potentially catastrophic complications, with a life-threatening risk of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Ascending aortic thrombus (AAT) in a nonaneurysmal aorta is an extremely rare event and has potentially catastrophic complications, with a life-threatening risk of myocardial infarction and cerebral embolization. This systematic review aims to elucidate the clinical manifestations and to compare the outcomes of anticoagulation therapy versus open aortic surgery for AAT.
METHODS
The MEDLINE/PubMed databases were extensively searched between 1995 and 2019. All relevant publications on AAT in adults were reviewed, and individual patient data were pooled in this meta-analysis. The primary outcome was AAT resolution. The adverse outcome variables were recurrent arterial embolic events, complications related to open aortic surgery, and mortality during the study period. Chi-squared test and logistic regression analysis were used to compare groups and identify any predictors of mortality.
RESULTS
Overall, 107 patients from 101 articles were included, of whom 29 patients who received anticoagulation therapy and 59 who underwent open aortic surgery were included in the outcome analysis. Among 29 patients treated with initial anticoagulation therapy, the persistence of AAT was observed in 11 patients (38%) and recurrent arterial embolization was developed in 6 patients (21%). All 11 patients in the anticoagulation group underwent secondary aortic surgery for the persistence of AAT with uneventful postoperative course. Compared with patients treated with primary aortic surgery, patients treated with initial anticoagulation therapy had higher risk of recurrent embolization (P = 0.002). No significant difference existed in the mortality rates between the groups (P = 0.106). Hemodynamic instability was an independent predictor of mortality (P = 0.008).
CONCLUSIONS
Anticoagulation therapy and open aortic surgery for AAT show similar results; however, open aortic surgery reliably removes AAT and reduces the risk of recurrent embolization compared with anticoagulation therapy. Furthermore, the preoperative hemodynamic status significantly influences the clinical outcome and is a strong predictor of prognosis.
Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Aorta; Aortic Diseases; Female; Fibrinolytic Agents; Hemodynamics; Humans; Male; Middle Aged; Postoperative Complications; Recurrence; Risk Assessment; Risk Factors; Thrombosis; Treatment Outcome; Vascular Surgical Procedures
PubMed: 33249131
DOI: 10.1016/j.avsg.2020.10.031