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Heart (British Cardiac Society) Jun 2019Vascular stiffness (VS) and vascular calcification (VC) are surrogate markers of vascular health associated with cardiovascular events. Vitamin K-dependent proteins... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Vascular stiffness (VS) and vascular calcification (VC) are surrogate markers of vascular health associated with cardiovascular events. Vitamin K-dependent proteins (VKDP) are associated with VS and VC and require vitamin K for activity. We conducted a systematic review and meta-analysis of: (1) the effect of vitamin K supplementation on VS and VC and (2) association of inactive VKDP levels with incident cardiovascular disease and mortality.
METHODS
Two authors searched MEDLINE and Embase databases and Cochrane and ISRCTN registries for studies of vitamin K clinical trials that measured effects on VC, VS or VKDP and longitudinal studies assessing effect of VKDP on incident CVD or mortality. Random effects meta-analyses were performed.
RESULTS
Thirteen controlled clinical trials (n=2162) and 14 longitudinal studies (n=10 726) met prespecified inclusion criteria. Vitamin K supplementation was associated with significant reduction in VC (-9.1% (95% CI -17.7 to -0.5); p=0.04) and VKDP (desphospho-uncarboxylated matrix Gla protein; -44.7% (95% CI -65.1 to -24.3), p<0.0001) and uncarboxylated osteocalcin; -12.0% (95% CI -16.7 to -7.2), p<0.0001) compared with control, with a non-significant improvement in VS. In longitudinal studies with median follow-up of 7.8 (IQR 4.9-11.3) years, VKDP levels were associated with a combined endpoint of CVD or mortality (HR 0.45 (95% CI 0.07 to 0.83), p=0.02).
CONCLUSIONS
Supplementation with vitamin K significantly reduced VC, but not VS, compared with control. The conclusions drawn are limited by small numbers of studies with substantial heterogeneity. VKDP was associated with combined endpoint of CVD or mortality. Larger clinical trials of effect of vitamin K supplementation to improve VC, VS and long-term cardiovascular health are warranted.
TRIAL REGISTRATION NUMBER
CRD42017060344.
Topics: Biomarkers; Dietary Supplements; Humans; Vascular Calcification; Vascular Diseases; Vitamin K; Vitamins
PubMed: 30514729
DOI: 10.1136/heartjnl-2018-313955 -
Journal of General Internal Medicine Feb 2019Vitamin K antagonist (VKA) anticoagulant use is suspected to increase the risk of bone fracture through inhibition of vitamin K-dependent cofactors of bone formation, an... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Vitamin K antagonist (VKA) anticoagulant use is suspected to increase the risk of bone fracture through inhibition of vitamin K-dependent cofactors of bone formation, an effect not seen with non-vitamin K antagonist oral anticoagulants (NOACs). The purpose of our systematic review and meta-analysis is to investigate the association between VKA use and fracture.
METHODS
We searched PubMed, EMBASE, and Cochrane Library for studies analyzing fracture in adults using VKAs versus controls. Two authors independently reviewed articles. We assessed for risk of bias using the Newcastle-Ottawa Quality Assessment Scale and the Cochrane Risk of Bias Tool and calculated pooled effects using random effects models.
RESULTS
We included 23 articles (22 observational studies and 1 randomized controlled trial), studying 1,121,582 subjects. There was no increased odds of fracture in VKA users versus controls (pooled OR 1.01, 95% CI 0.89, 1.14) or in VKA users versus NOAC users (pooled OR 0.95, 95% CI 0.78, 1.15). Subjects using a VKA for 1 year or longer did not have increased odds of fracture (pooled OR 1.07, 95% CI 0.90, 1.27). Compared to controls, there was increased odds of fracture in women (pooled OR 1.11, 95% CI 1.02, 1.21) and older VKA users (≥ 65) (pooled OR 1.07, 95% CI 1.01, 1.14).
DISCUSSION
We found no increase in odds of fracture in VKA users versus controls or NOAC users. There was a small increase in odds of fracture among female and elderly VKA users, which may not be clinically important when accounting for other considerations in choosing an anticoagulant. Our findings suggest that, when anticoagulation is necessary, fracture risk should not be a major consideration in choice of an agent. Future studies directly comparing VKA to NOAC users and studies with longer duration of VKA use may be needed.
Topics: Administration, Oral; Anticoagulants; Fractures, Bone; Humans; Observational Studies as Topic; Randomized Controlled Trials as Topic; Vitamin K
PubMed: 30511289
DOI: 10.1007/s11606-018-4758-2 -
European Journal of Medical Research Oct 2018To assess the frequency of left atrium/left atrial appendage (LA/LAA) thrombus under treatment with non-vitamin K oral anticoagulants (NOACs) in comparison with vitamin... (Meta-Analysis)
Meta-Analysis
Frequency of atrial thrombus formation in patients with atrial fibrillation under treatment with non-vitamin K oral anticoagulants in comparison to vitamin K antagonists: a systematic review and meta-analysis.
BACKGROUND
To assess the frequency of left atrium/left atrial appendage (LA/LAA) thrombus under treatment with non-vitamin K oral anticoagulants (NOACs) in comparison with vitamin K antagonists (VKAs) in patients with non-valvular atrial fibrillation (AF).
METHODS
PubMed, Web of Science™, EMBASE and the Cochrane Library databases were searched for studies comparing NOACs with VKAs in AF patients who underwent diagnostic transoesophageal echocardiography (TEE).
RESULTS
A total of four trials were considered eligible and were included in the meta-analysis. Four RCTs comprising n = 2397 AF patients (NOACs: n = 1412, VKAs: n = 985) were included in the meta-analysis. The frequency of LA/LAA thrombus formation under treatment with NOACs was similar to VKAs [odds ratio (OR) 1.14, 95% confidence intervals (95% CIs) 0.97-1.65, p = 0.48]. Both treatment groups revealed an approximately 5% frequency of thrombus formation, although a precise calculation is not possible due to Simpson paradox. Indications of heterogeneity between the included trials were not found (χ test p = 0.99, I = 0%).
CONCLUSIONS
The findings of this meta-analysis suggest that NOACs are similar to VKAs regarding the frequency of LA/LAA thrombus in patients with AF. An unknown number of patients in the original studies did not receive sufficient anticoagulation for at least 3 weeks prior to TEE examination, and therefore the present results should be interpreted with caution. Systematic review registration- http://www.crd.york.ac.uk/PROSPERO . Unique identifier: PROSPERO CRD42017059293.
Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Blood Coagulation; Heart Atria; Humans; PubMed; Thrombosis; Vitamin K
PubMed: 30352632
DOI: 10.1186/s40001-018-0350-9 -
Clinical and Applied... Dec 2018To perform a systematic review and network meta-analysis evaluating the efficacy and safety of low-molecular-weight heparins (LMWHs), vitamin K antagonists (VKAs), and... (Meta-Analysis)
Meta-Analysis
To perform a systematic review and network meta-analysis evaluating the efficacy and safety of low-molecular-weight heparins (LMWHs), vitamin K antagonists (VKAs), and direct-acting oral anticoagulants (DOACs) for the treatment of cancer-associated thrombosis (CAT). We searched MEDLINE, Cochrane Central Register of Controlled Trials, and conference abstracts through March 2018. Randomized controlled trials (RCTs) enrolling adults with CAT comparing 2 or more full-dose anticoagulants (LMWH, VKA, and DOAC) and evaluating recurrent venous thromboembolism (VTE), major bleeding, and/or all-cause mortality were included. Reviewers identified studies, extracted data, and assessed the quality of the evidence in duplicate. A frequentist network meta-analysis, which uses direct and indirect evidence to simultaneously compare multiple interventions, was performed using a random-effects approach. Results are reported as pooled relative risks (RRs) with 95% confidence intervals (CIs). We included 13 RCTs (n = 6292): 7 compared LMWHs with VKAs, 4 compared DOACs with VKAs, and 2 compared DOACs with LMWHs. The risk of recurrent VTE was significantly reduced by 28% and 54% with a DOAC compared to an LMWH and a VKA, respectively. Low-molecular-weight heparins significantly reduced the risk of recurrent VTE by 36% versus VKAs. The risk of major bleeding was 14% higher with DOACs compared to LMWHs and 15% and 25% lower with DOACs and LMWHs versus VKAs, although 95% CIs included unity for each. The risk of all-cause mortality appeared similar for all 3 comparisons (RR = 1.0 for each comparison). Direct-acting oral anticoagulants appeared superior in reducing recurrent VTE in patients with CAT compared to LMWH and VKAs, but an increased risk of major bleeding versus LMWH cannot be ruled out.
Topics: Administration, Oral; Anticoagulants; Heparin, Low-Molecular-Weight; Humans; Neoplasms; Practice Guidelines as Topic; Randomized Controlled Trials as Topic; Thrombosis; Vitamin K
PubMed: 30244595
DOI: 10.1177/1076029618800792 -
Scientific Reports Jul 2018To study supplementation effect of vitamin K (VK) alone or combined with other nutrients administered to pregnant women, we searched Cochrane Pregnancy and Childbirth... (Meta-Analysis)
Meta-Analysis
To study supplementation effect of vitamin K (VK) alone or combined with other nutrients administered to pregnant women, we searched Cochrane Pregnancy and Childbirth Group's Trials Register (till 22 January 2016, updated on 28 February 2018) including other resources. Two review authors independently assessed randomised or quasi-randomised controlled trials for inclusion, data extraction, accuracy, and risk of bias. We included older trials from high-income countries (six; 21,493 women-newborns), judged mostly as high or unclear bias risk. We could not assess high-risk e.g. epileptic women, but healthy women (different gestational ages) received varying VK dosages and duration. We meta-analysed neonatal bleeding (RR 1.16, 95% CI 0.59 to 2.29; P = 0.67) and maternal plasma VK1 (MD 2.46, 95% CI 0.98 to 3.93; P = 0.001). We found many outcomes were un-assessed e.g. perinatal death, maternal bleeding, healthcare utilization. Mostly newborns were included where VK found significantly effective for e.g. serum VK (mother-newborn), maternal breast milk VK. Few trials reported neonatal adverse side effects. The GRADE evidence quality was very low i.e. neonatal bleeding, neonatal jaundice, maternal plasma VK1. The intervention was favourable for maternal sera VK1 but remained uncertain for neonatal bleeding and other outcomes. The existing literature gaps warrant future investigations on un-assessed or inadequately reported outcomes.
Topics: Dietary Supplements; Female; Humans; Infant, Newborn; Milk, Human; Osteocalcin; Pregnancy; Pregnancy Outcome; Publication Bias; Risk; Vitamin K
PubMed: 30061633
DOI: 10.1038/s41598-018-29616-y -
British Journal of Haematology Oct 2018Guidelines advise performing a computed tomography head scan for all anticoagulated head injured patients, but the risk of intracranial haemorrhage (ICH) after a minor... (Meta-Analysis)
Meta-Analysis
Guidelines advise performing a computed tomography head scan for all anticoagulated head injured patients, but the risk of intracranial haemorrhage (ICH) after a minor head injury is unclear. We conducted a systematic review and meta-analysis to determine the incidence of ICH in anticoagulated patients presenting with a minor head injury and a Glasgow Coma Score (GCS) of 15. We followed Meta-Analyses and Systematic Reviews of Observational Studies guidelines. We included all prospective studies recruiting consecutive anticoagulated emergency patients presenting with a head injury. Anticoagulation included vitamin-K antagonists (warfarin, fluindione), direct oral anticoagulants (apixaban, rivaroxaban, dabigatran and edoxaban) and low molecular weight heparin. A total of five studies (including 4080 anticoagulated patients with a GCS of 15) were included in the analysis. The majority of patients took vitamin K antagonists (98·3%). There was significant heterogeneity between studies with regards to mechanism of injury and methods. The random effects pooled incidence of ICH was 8·9% (95% confidence interval 5·0-13·8%). In conclusion, around 9% of patients on vitamin K antagonists with a minor head injury develop ICH. There is little data on the risk of traumatic intracranial bleeding in patients who have a GSC 15 post-head injury and are prescribed a direct oral anticoagulant.
Topics: Anticoagulants; Craniocerebral Trauma; Factor Xa Inhibitors; Female; Heparin, Low-Molecular-Weight; Humans; Incidence; Intracranial Hemorrhages; Male; Prospective Studies; Vitamin K
PubMed: 30028001
DOI: 10.1111/bjh.15509 -
Cardiovascular Therapeutics Oct 2018Catheter ablation for atrial fibrillation (AF) is associated with a transitory increase in the risk of both thromboembolic and bleeding events. Evidence on the use of... (Meta-Analysis)
Meta-Analysis
AIMS
Catheter ablation for atrial fibrillation (AF) is associated with a transitory increase in the risk of both thromboembolic and bleeding events. Evidence on the use of nonvitamin K antagonist oral anticoagulants (NOACs) in patients undergoing AF ablation mostly comes from small observational studies, underpowered to detect differences in clinical outcomes between NOACs and vitamin K antagonists (VKAs) treated patients. This updated meta-analysis aimed to determine the safety and efficacy of periprocedural anticoagulation with NOACs compared with VKAs in AF patients undergoing catheter ablation.
METHODS
We searched MEDLINE, Cochrane library, and web sources for randomized and observational studies comparing periprocedural treatment with NOACs and VKAs in patients undergoing AF ablation. The primary safety endpoint was major bleeding events, and the primary efficacy endpoint was thromboembolic events (a composite of systemic thromboembolism, transient ischemic attack, and stroke).
RESULTS
A total of 29 studies with 12 644 patients were included in the meta-analysis. Overall, patients on NOACs had a significantly lower risk of major bleeding compared to VKAs either in observational studies (Peto OR 0.68; 95% CI: 0.48-0.95; P = 0.022; I = 20%) or in RCTs (Peto OR 0.30; 95% CI: 0.14-0.62; P = 0.001; I = 28%). Uninterrupted NOACs reduced the risk of major bleeding when compared to uninterrupted VKAs (Peto OR 0.66; 95% CI: 0.45-0.96; P = 0.028; I = 1%), similarly, interrupted NOACs lowered the risk of major bleeding compared to interrupted VKAs (Peto OR 0.29; 95% CI: 0.13-0.66; P = 0.003; I = 0%; P = 0.076). The rate of thromboembolic complications was very low and did not significantly differ between the study groups either in observational studies (Peto OR 0.91; 95% CI: 0.49-1.67; P = 0.755; I = 0%) or in RCTs (Peto OR 0.14; 95% CI: 0.01-1.30; P = 0.083; I = 0%).
CONCLUSIONS
Use of NOACs compared to VKAs significantly reduced the risk of bleeding in patients with AF ablation. Similarly, the risk of bleeding was lower with uninterrupted NOACs than with uninterrupted VKAs, and with interrupted NOACs than with interrupted VKAs. The rate of thromboembolic complications was extremely low in both study groups without any differences.
Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Blood Loss, Surgical; Catheter Ablation; Drug Administration Schedule; Humans; Patient Safety; Postoperative Hemorrhage; Risk Assessment; Risk Factors; Treatment Outcome; Venous Thromboembolism; Vitamin K
PubMed: 29971964
DOI: 10.1111/1755-5922.12457 -
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... Jun 2018Central venous catheter (CVC) placement increases the risk of thrombosis in people with cancer. Thrombosis often necessitates the removal of the CVC, resulting in... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Central venous catheter (CVC) placement increases the risk of thrombosis in people with cancer. Thrombosis often necessitates the removal of the CVC, resulting in treatment delays and thrombosis-related morbidity and mortality. This is an update of the Cochrane Review published in 2014.
OBJECTIVES
To evaluate the efficacy and safety of anticoagulation for thromboprophylaxis in people with cancer with a CVC.
SEARCH METHODS
We conducted a comprehensive literature search in May 2018 that included a major electronic search of Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (Ovid), and Embase (Ovid); handsearching of conference proceedings; checking of references of included studies; searching for ongoing studies; and using the 'related citation' feature in PubMed. This update of the systematic review was based on the findings of a literature search conducted on 14 May 2018.
SELECTION CRITERIA
Randomized controlled trials (RCTs) assessing the benefits and harms of unfractionated heparin (UFH), low-molecular-weight heparin (LMWH), vitamin K antagonists (VKA), or fondaparinux or comparing the effects of two of these anticoagulants in people with cancer and a CVC.
DATA COLLECTION AND ANALYSIS
Using a standardized form, we extracted data and assessed risk of bias. Outcomes included all-cause mortality, symptomatic catheter-related venous thromboembolism (VTE), pulmonary embolism (PE), major bleeding, minor bleeding, catheter-related infection, thrombocytopenia, and health-related quality of life (HRQoL). We assessed the certainty of evidence for each outcome using the GRADE approach (Balshem 2011).
MAIN RESULTS
Thirteen RCTs (23 papers) fulfilled the inclusion criteria. These trials enrolled 3420 participants. Seven RCTs compared LMWH to no LMWH (six in adults and one in children), six RCTs compared VKA to no VKA (five in adults and one in children), and three RCTs compared LMWH to VKA in adults.LMWH versus no LMWHSix RCTs (1537 participants) compared LMWH to no LMWH in adults. The meta-analyses showed that LMWH probably decreased the incidence of symptomatic catheter-related VTE up to three months of follow-up compared to no LMWH (risk ratio (RR) 0.43, 95% confidence interval (CI) 0.22 to 0.81; risk difference (RD) 38 fewer per 1000, 95% CI 13 fewer to 52 fewer; moderate-certainty evidence). However, the analysis did not confirm or exclude a beneficial or detrimental effect of LMWH on mortality at three months of follow-up (RR 0.82, 95% CI 0.53 to 1.26; RD 14 fewer per 1000, 95% CI 36 fewer to 20 more; low-certainty evidence), major bleeding (RR 1.49, 95% CI 0.06 to 36.28; RD 0 more per 1000, 95% CI 1 fewer to 35 more; very low-certainty evidence), minor bleeding (RR 1.35, 95% CI 0.62 to 2.92; RD 14 more per 1000, 95% CI 16 fewer to 79 more; low-certainty evidence), and thrombocytopenia (RR 1.03, 95% CI 0.80 to 1.33; RD 5 more per 1000, 95% CI 35 fewer to 58 more; low-certainty evidence).VKA versus no VKAFive RCTs (1599 participants) compared low-dose VKA to no VKA in adults. The meta-analyses did not confirm or exclude a beneficial or detrimental effect of low-dose VKA compared to no VKA on mortality (RR 0.99, 95% CI 0.64 to 1.55; RD 1 fewer per 1000, 95% CI 34 fewer to 52 more; low-certainty evidence), symptomatic catheter-related VTE (RR 0.61, 95% CI 0.23 to 1.64; RD 31 fewer per 1000, 95% CI 62 fewer to 51 more; low-certainty evidence), major bleeding (RR 7.14, 95% CI 0.88 to 57.78; RD 12 more per 1000, 95% CI 0 fewer to 110 more; low-certainty evidence), minor bleeding (RR 0.69, 95% CI 0.38 to 1.26; RD 15 fewer per 1000, 95% CI 30 fewer to 13 more; low-certainty evidence), premature catheter removal (RR 0.82, 95% CI 0.30 to 2.24; RD 29 fewer per 1000, 95% CI 114 fewer to 202 more; low-certainty evidence), and catheter-related infection (RR 1.17, 95% CI 0.74 to 1.85; RD 71 more per 1000, 95% CI 109 fewer to 356; low-certainty evidence).LMWH versus VKAThree RCTs (641 participants) compared LMWH to VKA in adults. The available evidence did not confirm or exclude a beneficial or detrimental effect of LMWH relative to VKA on mortality (RR 0.94, 95% CI 0.56 to 1.59; RD 6 fewer per 1000, 95% CI 41 fewer to 56 more; low-certainty evidence), symptomatic catheter-related VTE (RR 1.83, 95% CI 0.44 to 7.61; RD 15 more per 1000, 95% CI 10 fewer to 122 more; very low-certainty evidence), PE (RR 1.70, 95% CI 0.74 to 3.92; RD 35 more per 1000, 95% CI 13 fewer to 144 more; low-certainty evidence), major bleeding (RR 3.11, 95% CI 0.13 to 73.11; RD 2 more per 1000, 95% CI 1 fewer to 72 more; very low-certainty evidence), or minor bleeding (RR 0.95, 95% CI 0.20 to 4.61; RD 1 fewer per 1000, 95% CI 21 fewer to 95 more; very low-certainty evidence). The meta-analyses showed that LMWH probably increased the risk of thrombocytopenia compared to VKA at three months of follow-up (RR 1.69, 95% CI 1.20 to 2.39; RD 149 more per 1000, 95% CI 43 fewer to 300 more; moderate-certainty evidence).
AUTHORS' CONCLUSIONS
The evidence was not conclusive for the effect of LMWH on mortality, the effect of VKA on mortality and catheter-related VTE, and the effect of LMWH compared to VKA on mortality and catheter-related VTE. We found moderate-certainty evidence that LMWH reduces catheter-related VTE compared to no LMWH. People with cancer with CVCs considering anticoagulation should balance the possible benefit of reduced thromboembolic complications with the possible harms and burden of anticoagulants.
Topics: Adult; Anticoagulants; Catheter-Related Infections; Catheterization, Central Venous; Child; Heparin; Heparin, Low-Molecular-Weight; Humans; Neoplasms; Randomized Controlled Trials as Topic; Secondary Prevention; Thrombocytopenia; Venous Thrombosis; Vitamin K
PubMed: 29856471
DOI: 10.1002/14651858.CD006468.pub6 -
PloS One 2018Vitamin K antagonist (VKA) therapy is safer and more effective when patients have a high time within the therapeutic range and low international normalised ratio... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Vitamin K antagonist (VKA) therapy is safer and more effective when patients have a high time within the therapeutic range and low international normalised ratio variability. The SAMe-TT2R2 score aims to identify those at risk for poor VKA control.
OBJECTIVES
To evaluate the predictive value and clinical usefulness of the SAMe-TT2R2 score to identify those at risk for poor VKA control.
METHODS
We performed a systematic review in MEDLINE and Embase for original research papers assessing the SAMe-TT2R2's relation to poor TTR. We performed a meta-analysis where scores ≥ 2 and ≥ 3 predicting TTR < 70%. When studies evaluated other cutoffs for TTR or SAMe-TT2R2, they were harmonised by multiple simulations with patient characteristics from the individual studies, if the data were available.
RESULTS
16 studies were identified and used in the meta-analysis: 4 and 2 times directly, 8 and 8 times harmonised for scores ≥ 2 and ≥ 3, respectively (not all studies provided information about both cutoffs). The sensitivities and specificities were too heterogeneous to pool. The positive likelihood ratios were 1.25 (1.14-1.38) for a score ≥ 2, and 1.24 (1.09-1.40) for a score ≥ 3; the negative ones were 0.87 (0.82-0.93) and 0.96 (0.91-1.02), respectively. This shows that the post-test probabilities hardly differ from the prior probability (prevalence).
CONCLUSION
The SAMe-TT2R2 score does predict low TTR, but the effect is small. Its effect on individual patients is too limited to be clinically useful.
Topics: Anticoagulants; Atrial Fibrillation; Blood Coagulation; Humans; International Normalized Ratio; Likelihood Functions; Risk; Venous Thromboembolism; Vitamin K
PubMed: 29534092
DOI: 10.1371/journal.pone.0194208