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The Cochrane Database of Systematic... Jul 2014Cancer increases the risk of thromboembolic events in patients including those receiving anticoagulation treatments. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Cancer increases the risk of thromboembolic events in patients including those receiving anticoagulation treatments.
OBJECTIVES
To compare the efficacy and safety of low molecular weight heparin (LMWH) and oral anticoagulants for the long-term treatment of venous thromboembolism (VTE) in patients with cancer.
SEARCH METHODS
We conducted a comprehensive search for studies of anticoagulation in cancer patients including 1. a February 2013 electronic search of: the Cochrane Central Register of Controlled Trials (CENTRAL Issue 12, 2012), MEDLINE, and EMBASE; 2. a handsearch of conference proceedings; 3. checking of references of included studies; 4. use of the 'related citation' feature in PubMed; and 5. a search of clinicaltrials.gov for ongoing studies.
SELECTION CRITERIA
We included randomized controlled trials (RCTs) comparing long-term treatment with LMWH versus oral anticoagulants (vitamin K antagonist (VKA) or ximelagatran) in patients with cancer and symptomatic objectively confirmed VTE.
DATA COLLECTION AND ANALYSIS
Using a standardized data form, we extracted data on methodological quality, participants, interventions and outcomes of interest: survival, recurrent VTE, major bleeding, minor bleeding, thrombocytopenia, and postphlebitic syndrome. We assessed the quality of evidence at the outcome level following the GRADE approach.
MAIN RESULTS
Of 9559 identified citations, 10 RCTs (11 reports) were eligible and reported data for 1981 patients with cancer. We excluded 14 studies in which patients with cancer constituted study subgroups, but did not report outcome data for them. Meta-analysis of seven RCTs comparing LMWH with VKA found no statistically significant survival benefit (hazard ratio (HR) 0.96; 95% confidence interval (CI) 0.81 to 1.14) but a statistically significant reduction in VTE (HR 0.47; 95% CI 0.32 to 0.71). The remaining findings did not exclude a beneficial or harmful effect of LMWH compared with VKA for the outcomes of major bleeding (RR 1.07; 95% CI 0.52 to 2.19), minor bleeding (RR 0.89; 95% CI 0.51 to 1.55), or thrombocytopenia (RR 0.98; 95% CI 0.57 to 1.66). We judged the quality of evidence as low for mortality, major bleeding, and minor bleeding, and as moderate for recurrent VTE.One RCT comparing dabigatran with VKA did not exclude beneficial or harmful effects of one agent over the other. One RCT comparing six months' extension of anticoagulation with 18 months of ximelagatran 24 mg twice daily versus no extended ximelagatran did not exclude beneficial or harmful effects for the outcomes of reduction in VTE, mortality, and minor bleeding. One RCT comparing once-weekly subcutaneous injection of idraparinux for three or six months versus standard treatment (parenteral anticoagulation followed by warfarin or acenocoumarol) suggested a reduction in recurrent VTE (HR 0.39; 95% CI 0.14 to 1.11) at six months, but did not exclude beneficial or harmful effects for the outcomes of mortality (HR 0.99; 95% CI 0.66 to 1.48) and major bleeding (RR 1.04; 95% CI 0.39 to 2.83).
AUTHORS' CONCLUSIONS
For the long-term treatment of VTE in patients with cancer, LMWH compared with VKA reduces venous thromboembolic events but not mortality. The decision for a patient with cancer and VTE to start long-term LMWH versus oral anticoagulation should balance the benefits and harms and integrate the patient's values and preferences for the important outcomes and alternative management strategies.
Topics: Administration, Oral; Anticoagulants; Azetidines; Benzimidazoles; Benzylamines; Dabigatran; Heparin, Low-Molecular-Weight; Humans; Neoplasms; Oligosaccharides; Randomized Controlled Trials as Topic; Venous Thromboembolism; Vitamin K; beta-Alanine
PubMed: 25004410
DOI: 10.1002/14651858.CD006650.pub4 -
The Cochrane Database of Systematic... Jun 2018Cancer increases the risk of thromboembolic events, especially in people receiving anticoagulation treatments. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Cancer increases the risk of thromboembolic events, especially in people receiving anticoagulation treatments.
OBJECTIVES
To compare the efficacy and safety of low molecular weight heparins (LMWHs), direct oral anticoagulants (DOACs) and vitamin K antagonists (VKAs) for the long-term treatment of venous thromboembolism (VTE) in people with cancer.
SEARCH METHODS
We conducted a literature search including a major electronic search of the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 1), MEDLINE (Ovid), and Embase (Ovid); handsearching conference proceedings; checking references of included studies; use of the 'related citation' feature in PubMed and a search for ongoing studies in trial registries. As part of the living systematic review approach, we run searches continually, incorporating new evidence after it is identified. Last search date 14 May 2018.
SELECTION CRITERIA
Randomized controlled trials (RCTs) assessing the benefits and harms of long-term treatment with LMWHs, DOACs or VKAs in people with cancer and symptomatic VTE.
DATA COLLECTION AND ANALYSIS
We extracted data in duplicate on study characteristics and risk of bias. Outcomes included: all-cause mortality, recurrent VTE, major bleeding, minor bleeding, thrombocytopenia, and health-related quality of life (QoL). We assessed the certainty of the evidence at the outcome level following the GRADE approach (GRADE handbook).
MAIN RESULTS
Of 15,785 citations, including 7602 unique citations, 16 RCTs fulfilled the eligibility criteria. These trials enrolled 5167 people with cancer and VTE.Low molecular weight heparins versus vitamin K antagonistsEight studies enrolling 2327 participants compared LMWHs with VKAs. Meta-analysis of five studies probably did not rule out a beneficial or harmful effect of LMWHs compared to VKAs on mortality up to 12 months of follow-up (risk ratio (RR) 1.00, 95% confidence interval (CI) 0.88 to 1.13; risk difference (RD) 0 fewer per 1000, 95% CI 45 fewer to 48 more; moderate-certainty evidence). Meta-analysis of four studies did not rule out a beneficial or harmful effect of LMWHs compared to VKAs on major bleeding (RR 1.09, 95% CI 0.55 to 2.12; RD 4 more per 1000, 95% CI 19 fewer to 48 more, moderate-certainty evidence) or minor bleeding (RR 0.78, 95% CI 0.47 to 1.27; RD 38 fewer per 1000, 95% CI 92 fewer to 47 more; low-certainty evidence), or thrombocytopenia (RR 0.94, 95% CI 0.52 to 1.69). Meta-analysis of five studies showed that LMWHs probably reduced the recurrence of VTE compared to VKAs (RR 0.58, 95% CI 0.43 to 0.77; RD 53 fewer per 1000, 95% CI 29 fewer to 72 fewer, moderate-certainty evidence).Direct oral anticoagulants versus vitamin K antagonistsFive studies enrolling 982 participants compared DOACs with VKAs. Meta-analysis of four studies may not rule out a beneficial or harmful effect of DOACs compared to VKAs on mortality (RR 0.93, 95% CI 0.71 to 1.21; RD 12 fewer per 1000, 95% CI 51 fewer to 37 more; low-certainty evidence), recurrent VTE (RR 0.66, 95% CI 0.33 to 1.31; RD 14 fewer per 1000, 95% CI 27 fewer to 12 more; low-certainty evidence), major bleeding (RR 0.77, 95% CI 0.38 to 1.57, RD 8 fewer per 1000, 95% CI 22 fewer to 20 more; low-certainty evidence), or minor bleeding (RR 0.84, 95% CI 0.58 to 1.22; RD 21 fewer per 1000, 95% CI 54 fewer to 28 more; low-certainty evidence). One study reporting on DOAC versus VKA was published as abstract so is not included in the main analysis.Direct oral anticoagulants versus low molecular weight heparinsTwo studies enrolling 1455 participants compared DOAC with LMWH. The study by Raskob did not rule out a beneficial or harmful effect of DOACs compared to LMWH on mortality up to 12 months of follow-up (RR 1.07, 95% CI 0.92 to 1.25; RD 27 more per 1000, 95% CI 30 fewer to 95 more; low-certainty evidence). The data also showed that DOACs may have shown a likely reduction in VTE recurrence up to 12 months of follow-up compared to LMWH (RR 0.69, 95% CI 0.47 to 1.01; RD 36 fewer per 1000, 95% CI 62 fewer to 1 more; low-certainty evidence). DOAC may have increased major bleeding at 12 months of follow-up compared to LMWH (RR 1.71, 95% CI 1.01 to 2.88; RD 29 more per 1000, 95% CI 0 fewer to 78 more; low-certainty evidence) and likely increased minor bleeding up to 12 months of follow-up compared to LMWH (RR 1.31, 95% CI 0.95 to 1.80; RD 35 more per 1000, 95% CI 6 fewer to 92 more; low-certainty evidence). The second study on DOAC versus LMWH was published as an abstract and is not included in the main analysis.Idraparinux versus vitamin K antagonistsOne RCT with 284 participants compared once-weekly subcutaneous injection of idraparinux versus standard treatment (parenteral anticoagulation followed by warfarin or acenocoumarol) for three or six months. The data probably did not rule out a beneficial or harmful effect of idraparinux compared to VKAs on mortality at six months (RR 1.11, 95% CI 0.78 to 1.59; RD 31 more per 1000, 95% CI 62 fewer to 167 more; moderate-certainty evidence), VTE recurrence at six months (RR 0.46, 95% CI 0.16 to 1.32; RD 42 fewer per 1000, 95% CI 65 fewer to 25 more; low-certainty evidence) or major bleeding (RR 1.11, 95% CI 0.35 to 3.56; RD 4 more per 1000, 95% CI 25 fewer to 98 more; low-certainty evidence).
AUTHORS' CONCLUSIONS
For the long-term treatment of VTE in people with cancer, evidence shows that LMWHs compared to VKAs probably produces an important reduction in VTE and DOACs compared to LMWH, may likely reduce VTE but may increase risk of major bleeding. Decisions for a person with cancer and VTE to start long-term LMWHs versus oral anticoagulation should balance benefits and harms and integrate the person's values and preferences for the important outcomes and alternative management strategies.Editorial note: this is a living systematic review (LSR). LSRs offer new approaches to review updating in which the review is continually updated, incorporating relevant new evidence as it becomes available. Please refer to the Cochrane Database of Systematic Reviews for the current status of this review.
Topics: Administration, Oral; Anticoagulants; Azetidines; Benzimidazoles; Benzylamines; Dabigatran; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Neoplasms; Oligosaccharides; Randomized Controlled Trials as Topic; Venous Thromboembolism; Vitamin K; beta-Alanine
PubMed: 29920657
DOI: 10.1002/14651858.CD006650.pub5 -
The Cochrane Database of Systematic... Sep 2012People who have had a transient ischaemic attack (TIA) or non-disabling ischaemic stroke have an annual risk of major vascular events of between 4% and 11%. Aspirin... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
People who have had a transient ischaemic attack (TIA) or non-disabling ischaemic stroke have an annual risk of major vascular events of between 4% and 11%. Aspirin reduces this risk by 20% at most. Secondary prevention trials after myocardial infarction indicate that treatment with vitamin K antagonists is associated with a risk reduction approximately twice that of treatment with antiplatelet therapy.
OBJECTIVES
To compare the efficacy and safety of vitamin K antagonists and antiplatelet therapy in the secondary prevention of vascular events after cerebral ischaemia of presumed arterial origin.
SEARCH METHODS
We searched the Cochrane Stroke Group Trials Register (last searched 15 September 2011), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 3), MEDLINE (2008 to September 2011) and EMBASE (2008 to September 2011). In an effort to identify further relevant trials we searched ongoing trials registers and reference lists. We also contacted authors of published trials for further information and unpublished data.
SELECTION CRITERIA
Randomised trials of oral anticoagulant therapy with vitamin K antagonists (warfarin, phenprocoumon or acenocoumarol) versus antiplatelet therapy for long-term secondary prevention after recent transient ischaemic attack or minor ischaemic stroke of presumed arterial origin.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected trials, assessed trial quality and extracted data.
MAIN RESULTS
We included eight trials with a total of 5762 participants. The data showed that anticoagulants (in any intensity) are not more efficacious in the prevention of vascular events than antiplatelet therapy (medium intensity anticoagulation: relative risk (RR) 0.80, 95% confidence interval (CI) 0.56 to 1.14; high intensity anticoagulation: RR 1.02, 95% CI 0.49 to 2.13). There is no evidence that treatment with low intensity anticoagulation gives a higher bleeding risk than treatment with antiplatelet agents: RR 1.27 (95% CI 0.79 to 2.03). However, it was clear that medium and high intensity anticoagulation with vitamin K antagonists, with an INR of 2.0 to 4.5, were not safe because they yielded a higher risk of major bleeding complications (medium intensity anticoagulation: RR 1.93, 95% CI 1.27 to 2.94; high intensity anticoagulation: RR 9.0, 95% CI 3.9 to 21).
AUTHORS' CONCLUSIONS
For the secondary prevention of further vascular events after TIA or minor stroke of presumed arterial origin, there is sufficient evidence to conclude that vitamin K antagonists in any dose are not more efficacious than antiplatelet therapy and that medium and high intensity anticoagulation leads to a significant increase in major bleeding complications.
Topics: Administration, Oral; Anticoagulants; Cause of Death; Hemorrhage; Humans; International Normalized Ratio; Ischemic Attack, Transient; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Secondary Prevention; Stroke; Vitamin K
PubMed: 22972051
DOI: 10.1002/14651858.CD001342.pub3 -
Archivio Italiano Di Urologia,... Oct 2023Renal artery infarction (RI) is the presence of blood clot in the main renal artery or its branches causing complete or partial obstruction of the blood supply. Its...
AIM
Renal artery infarction (RI) is the presence of blood clot in the main renal artery or its branches causing complete or partial obstruction of the blood supply. Its etiology is either related with disorders of the renal vasculature or with cardiovascular diseases. Recently, the SARSCoV- 2 virus is an emerging cause of thromboembolic events and the incidence of RI is anticipated to increase after the pandemic.
METHODS
A systematic review based on COVID-19 associated RI was conducted.
PROTOCOL
A systematic review of the Medline/Pubmed and Scopus databases was conducted in accordance to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (the PRISMA statement). Search strategy and information sources: A hand-search was performed using the terms "SARS-Cov-2" OR "COVID-19" AND "renal thrombosis" OR "renal infarction" OR "renal "thromboembolism".
ELIGIBILITY CRITERIA
all types of publications (case reports, case series, letters to the editor, short communications) were evaluated for relevance. Inclusion criteria were: confirmed SARS-Cov-2 infection irrespectively of the age, diagnosis of RI during or after the onset of viral infection, and exclusion of other potential causes of thromboembolic event except of SARS-Cov-2. Patients with renal transplantation were also considered. Study criteria selection: after checking for relevance based on the title and the abstract, the full texts of the selected papers were retrieved and were further evaluated. Duplicated and irrelevant cases were excluded. Any disagreement was resolved by consensus with the involvement of a third reviewer. Quality of studies: The assessment of the quality case reports was based on four different domains: selection, ascertainment, casualty and reporting. Each paper was classified as "Good", "Moderate" and "Poor" for any of the four domains. Data extractions: Crucial data for the conduct of the study were extracted including: age, sex, time from SARS-Cov-2 infection till RI development, medical history, previous or current antithrombotic protection or treatment, laterality and degree of obstruction, other sites of thromboembolism, treatment for thromboembolism and SARS-Cov-2 and final outcome.
DATA ANALYSIS
methods of descriptive statistics were implicated for analysis and presentation of the data.
RESULTS
The systematic review retrieved 35 cases in 33 reports. In most cases, RI was diagnosed within a month from the SARSCov- 2 infection albeit 17 out of 35 patients were receiving or had recently received thromboprophylaxis. Right, left, bilateral and allograft obstruction was diagnosed in 7, 15, 8 and 5 patients respectively. 17 cases experienced additional extrarenal thromboembolism primarily in aorta, spleen, brain and lower limbs. Low molecular weight heparins (LMWH) (usually 60-80 mg enoxaparine bid) was the primary treatment, followed by combinations of unfractionated heparin and salicylic acid, apixaban and rivaraxaban, warfarin, acenocoumarol or clopidogrel. Kidney replacement therapy was offered to five patients while invasive therapies with thrombus aspiration or catheter directed thrombolysis were performed in two. Regarding the outcomes, five of the patients died. The total renal function was preserved in 17 cases and renal impairment with or without hemodialysis was recorded in 5 patients, two of them having lost their kidney allografts.
LIMITATIONS
The majority of included studies are of moderate quality. The results and the conclusions are based on case-reports only and crucial data are dissimilarly presented or missing through the relevant publications.
CONCLUSIONS
Thromboprophylaxis may not offer adequate protection against SARS-Cov-2 induced thrombosis. Most patients could be effectively treated with conservative measures, while in more severe cases aggressive treatment could be recommended.
IMPLICATIONS OF KEY FINDINGS
Therapeutic doses of LMWH could be considered for protection against RI in SARS-Cov-2 cases. Interventional treatment could be offered in a minority of more severe cases after carful balancing the risks and benefits.
Topics: Humans; SARS-CoV-2; COVID-19; Heparin, Low-Molecular-Weight; Anticoagulants; Heparin; Renal Artery; Venous Thromboembolism; Thrombosis; Infarction
PubMed: 37791549
DOI: 10.4081/aiua.2023.11625 -
Cardiology and Therapy Dec 2016Economic evaluations are becoming increasingly important due to limitations in economic resources, the expense of many new treatments, the need to allocate health...
INTRODUCTION
Economic evaluations are becoming increasingly important due to limitations in economic resources, the expense of many new treatments, the need to allocate health spending as effectively as possible, and the need to inform decision makers. Based on the data from the apixaban studies (ARISTOTLE and AVERROES), several economic evaluations have been performed in various countries to demonstrate the efficacy of apixaban versus warfarin and aspirin or other new oral anticoagulants (NOACs) for preventing stroke in patients with non-valvular atrial fibrillation (NVAF).The aim of this study was to perform a systematic literature review of published economic evaluations with apixaban in the indication of stroke prevention in patients with NVAF.
METHODS
A search in PubMed, Cochrane Library, Google Scholar, and Index Medicus Español was conducted in June 2015. Inclusion and exclusion criteria were established. The main characteristics were recorded for all relevant articles after being reviewed. In addition, a weighted version of the Drummond's checklist was used to further assess the quality of the selected studies.
RESULTS
After review, 26 cost-effectiveness analyses through Markov models were included; the identified economic evaluations represent different willingness-to-pay (WTP) thresholds, discount rates, medical costs, and healthcare systems. Apixaban was compared with warfarin/acenocoumarol in 7 of them (27%), with warfarin/NOACs in 14 (54%), with aspirin in 2 (8%), and with warfarin/aspirin in 3 (11%). Models were conducted from Europe (69%), USA (23%), Australia (4%), and Latin America (4%). All models reported cost/quality-adjusted life years (QALYs) gained, 92% reported using a payer perspective, and 8% using a societal perspective; the median quality score of the selected studies was 89 (out of 119), with a range of 55-103. In models performed in Europe, incremental cost-effectiveness ratios (ICERs) of apixaban versus warfarin ranged from €5607/QALY to €57,245/QALY, while ICERs versus aspirin ranged from being dominant to €7334/QALY. In models carried out in the USA, ICERs of apixaban versus warfarin ranged from being dominant to $93,063/QALY.
CONCLUSION
Different cost-effectiveness analyses suggest that apixaban is a cost-effective therapeutic option according to the WTP thresholds used in countries where cost-effectiveness analyses, were performed.
FUNDING
BMS and Pfizer.
PubMed: 27457613
DOI: 10.1007/s40119-016-0066-2