Venous Thromboembolism Recurrence after a First Episode of Provoked Venous Thrombosis Due to a Transient Risk Factor. A Systematic Review of the Literature

Abstract Background: Venous thromboembolism (VTE) has a tendency to recur after anticoagulation is stopped. The optimal duration of anticoagulation is influenced by the risk of recurrence: indefinite anticoagulation is recommended after a first VTE associated with a persistent and strong risk factor (e.g. cancer), whereas three months of anticoagulation is adequate if VTE was provoked by a transient risk factor (e.g. surgery). The optimal duration of anticoagulation after a first unprovoked VTE is, however, still a matter of debate. An attractive approach is to identify subgroups of patients with unprovoked VTE who have a high risk of recurrence and treat them with prolonged anticoagulation, and subgroups with a lower risk of recurrence and treat them for only three months. A critical issue, therefore, is to determine a cut-off value for risk of recurrence that is low enough to justify stopping anticoagulant therapy at three months (i.e., a rate of recurrence that is acceptable to patients and physicians). We propose that the rate of recurrence after VTE that was provoked by a transient risk factor represents such a value. Aim of the study: To accurately estimate the risk of recurrence in patients with VTE provoked by a transient risk factor who have completed at least three months of anticoagulant therapy. Materials and Methods: Medline, Embase and Cochrane Collaboration Registry of Randomized Trials were searched for any studies reporting the recurrence rate of VTE after a first episode of VTE associated with a transient risk factor (surgery, trauma, plaster, bed rest, pregnancy, puerperium, hormone treatment). The references of retrieved articles were scanned for any additional relevant studies. Studies were included if enrolling patients met the following criteria: a first episode of VTE provoked by a transient risk factor; a course of at least three months of oral anticoagulant therapy; a follow up of 12 or 24 months after treatment discontinuation with assessment of VTE recurrence rate. Recurrence rate, or data that allowed its calculation, needed to be reported. An overall estimate of the recurrence rate was calculated following Laird (Stats Med 1990), having predefined to use a fixed-effect model if no heterogeneity was found among the studies or a random-effect model otherwise. The inverse variance method was used to calculate weights for the studies. Results: The literature search yield 1089 references. After careful scanning of the potentially relevant papers, 15 papers were included in the final analysis. All studies except one were prospective. 12/15 and 11/15 studies reported data about the recurrence rate at 12 and 24 months, respectively. Overall there were 106 events among of 2217 patients at 12 months and 160 events among 2321 patients at 24 months. The pooled recurrence rate was 4.0% (95% C.I. 3.0%–5.2%) at 12 months and 6.7% (95% C.I. 5.2%–8.6%) at 24 months. Conclusion: The cumulative risk of recurrence in patients with VTE provoked by a reversible risk factor is 6.7% (95% C.I. 5.2%–8.6%) two years after anticoagulant withdrawal. We suggest that it acceptable to stop anticoagulant therapy after three months in subgroups of patients with unprovoked VTE who have been shown to have a risk of recurrence that is similar to, or lower than, this rate.

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P3850Impact of sex and risk factors for venous thromboembolism on the clinical course of first acute venous thromboembolism. Insights from the PREFER in VTE

European Heart Journal ◽

10.1093/eurheartj/ehz745.0690 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

M Giustozzi ◽

S Barco ◽

L Valerio ◽

F A Klok ◽

M C Vedovati ◽

...

Keyword(s):

Risk Factors ◽

Risk Factor ◽

Venous Thromboembolism ◽

Baseline Risk ◽

Major Surgery ◽

First Episode ◽

Risk Of Recurrence ◽

Recurrent Vte ◽

The Impact

Abstract Introduction The interaction between sex and specific provoking risk factors for venous thromboembolism (VTE) may influence initial presentation and prognosis. Purpose We investigated the impact of sex on the risk of recurrence across subgroups of patients with first VTE classified according to baseline risk factors. Methods PREFER in VTE was an international, non-interventional registry (2013–2015) including patients with a first episode of acute symptomatic objectively diagnosed VTE. We studied the risk of recurrence in patients classified according to baseline provoking risk factors for VTE consisted of i) major transient (major surgery/trauma, >5 days in bed), ii) minor transient (pregnancy or puerperium, estroprogestinic therapy, prolonged immobilization, current infection or bone fracture/soft tissue trauma); iii) unprovoked events, iv) active cancer-associated VTE. Results A total of 3,455 patients diagnosed with first acute VTE were identified, of whom 1,623 (47%) were women. The percentage of patients with a major transient risk factor was 22.2% among women and 19.7% among men. Minor transient risk factors were present in 21.3% and 12.4%, unprovoked VTE in 51.6% and 61.6%, cancer-associated VTE in 4.9% of women and 6.3% of men, respectively. The proportions of cases treated with Vitamin-K antagonists (VKAs) and direct oral anticoagulants (DOACs) were similar between sexes. Median length of treatment of VKAs was 181.5 and 182.0 days and of DOACs was 113.0 and 155.0 days in women and men, respectively. At 12-months of follow-up, VTE recurrence was reported in 74 (4.8%) women and 80 (4.5%) men. Table 1 shows the sex-specific proportion of recurrences by VTE risk factor categories. Table 1 Major Transient (n=722) Minor transient (n=573) Cancer-associated (n=195) Unprovoked (1965) Women (361) Men (361) OR (95% CI) Women (346) Men (227) OR (95% CI) Women (79) Men (116) OR (95% CI) Women (837) Men (1128) OR (95% CI) One-year follow-up, n (N%) Recurrent VTE, 21 (6.2) 10 (2.9) 0.46 (0.2; 0.9) 9 (2.7) 12 (5.4) 2.09 (0.9; 5.0) 6 (8.0) 5 (4.5) 0.54 (0.2; 1.9) 38 (4.7) 53 (4.7) 1.03 (0.7; 1.6) Major bleeding, 6 (1.8) 5 (1.5) 0.83 (0.3; 2.7) 5 (1.5) 1 (0.5) 0.30 (0.1; 2.6) 1 (1.3) 3 (2.7) 2.07 (0.2; 20) 10 (1.2) 15 (1.4) 1.11 (0.6; 2.4) All-cause death, 37 (10.2) 31 (8.5) 0.82 (0.5; 1.4) 10 (2.9) 14 (6.2) 2.21 (0.9; 5.1) 26 (32.9) 49 (42.2) 1.49 (0.8; 2.7) 33 (3.9) 30 (2.7) 0.66 (0.4; 1.1) Conclusions The proportion of patients with recurrent VTE events after first acute symptomatic VTE provoked by transient risk factors was not negligible during the first year of follow-up during in both women and men. These results may have implications on the decision whether to consider extended anticoagulant therapy in selected patients with provoked events. Acknowledgement/Funding This study was funded by Daiichi Sankyo.

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Risk of Recurrence after a First Episode of Symptomatic Venous Thromboembolism Provoked by a Transient Risk Factor: A Systematic Review

Journal of Emergency Medicine ◽

10.1016/j.jemermed.2010.12.003 ◽

2011 ◽

Vol 40 (3) ◽

pp. 360-361

Author(s):

Deborah Vinton

Keyword(s):

Systematic Review ◽

Risk Factor ◽

Venous Thromboembolism ◽

First Episode ◽

Risk Of Recurrence

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Metabolic syndrome in antipsychotic-naïve patients with first-episode psychosis: a systematic review and meta-analysis

Psychological Medicine ◽

10.1017/s0033291721002853 ◽

2021 ◽

pp. 1-14

Author(s):

Nathalia Garrido-Torres ◽

Idalino Rocha-Gonzalez ◽

Luis Alameda ◽

Aurora Rodriguez-Gangoso ◽

Ana Vilches ◽

...

Keyword(s):

Systematic Review ◽

Metabolic Syndrome ◽

Meta Analysis ◽

Random Effect ◽

Random Effect Model ◽

First Episode ◽

Effect Model ◽

Caucasian Origin ◽

Drug Naïve ◽

Meta Analyses

Abstract Background It is unclear what the prevalence of metabolic syndrome (MetS) in drug-naïve first-episode of psychosis (FEP) is, as previous meta-analyses were conducted in minimally exposed or drug-naïve FEP patients with psychotic disorder at any stage of the disease; thus, a meta-analysis examining MetS in naïve FEP compared with the general population is needed. Methods Studies on individuals with FEP defined as drug-naïve (0 days exposure to antipsychotics) were included to conduct a systematic review. A meta-analysis of proportions for the prevalence of MetS in antipsychotic-naïve patients was performed. Prevalence estimates and 95% CI were calculated using a random-effect model. Subgroup analyses and meta-regressions to identify sources and the amount of heterogeneity were also conducted. Results The search yielded 4143 articles. After the removal of duplicates, 2473 abstracts and titles were screened. At the full-text stage, 112 were screened, 18 articles were included in a systematic review and 13 articles in the main statistical analysis. The prevalence of MetS in naïve (0 days) FEP is 13.2% (95% CI 8.7–19.0). Ethnicity accounted for 3% of the heterogeneity between studies, and diagnostic criteria used for MetS accounted for 7%. When compared with controls matched by sex and age, the odds ratio is 2.52 (95% CI 1.29–5.07; p = 0.007). Conclusions Our findings of increased rates of MetS in naïve FEP patients suggest that we are underestimating cardiovascular risk in this population, especially in those of non-Caucasian origin. Our findings support that altered metabolic parameters in FEPs are not exclusively due to antipsychotic treatments.

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Lipoprotein(a) as a Risk Factor for Venous Thromboembolism: A Systematic Review and Meta-analysis of the Literature

Seminars in Thrombosis and Hemostasis ◽

10.1055/s-0036-1598002 ◽

2017 ◽

Vol 43 (06) ◽

pp. 614-620 ◽

Cited By ~ 16

Author(s):

Vera Gessi ◽

Rossella Marcucci ◽

Monica Gianni ◽

Anna Grandi ◽

Massimo Franchini ◽

...

Keyword(s):

Systematic Review ◽

Risk Factor ◽

Venous Thromboembolism ◽

Case Reports ◽

Random Effect ◽

Random Effect Model ◽

Case Series ◽

Lipoprotein A ◽

Increased Risk ◽

Venous Thromboembolic Events

AbstractElevated plasma levels of lipoprotein(a) (Lp(a)) are associated with increased cardiovascular risk in several clinical studies. However, there is a lack of data supporting a positive association between elevated Lp(a) levels and venous thromboembolism (VTE). Thus, we conducted a systematic review of the literature to better clarify its role as a risk factor for VTE. Medline and the Embase (up to May 2015) electronic databases were used to identify potentially eligible studies. Studies measuring Lp(a) values in adult patients with deep vein thrombosis and/or pulmonary embolism and in a population of patients without a VTE were selected. Studies on patients with major venous thromboembolic events occurring at other unusual site, case reports, and case series were excluded. The odds ratios (ORs) of the association between high values of Lp(a) and VTE and the weighted mean difference (WMD) in Lp(a) levels in cases and in controls were calculated using a random-effect model. Results were presented with 95% confidence interval (CI). Fourteen studies for a total of more than 14,000 patients were finally included in our analysis. Lp(a) was slightly but significantly associated with an increased risk of VTE (OR: 1.56, 95% CI: 1.36, 1.79; 10 studies, 13,541 patients). VTE patients had significantly higher Lp(a) values compared with controls (WMD: 14.46 mg/L, 95% CI: 12.14, 16.78; 4 studies, 470 patients). Lp(a) appeared to be significantly associated with increased risk of VTE. However, Lp(a) levels were only slightly increased in VTE patients compared with controls.

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Prevalence of Venous Thromboembolism in Critically Ill Patients With Coronavirus Disease 2019: A Meta-Analysis

Frontiers in Medicine ◽

10.3389/fmed.2021.603558 ◽

2021 ◽

Vol 8 ◽

Author(s):

Changgang Wu ◽

Yunlong Liu ◽

Xiangjing Cai ◽

Wenming Zhang ◽

Yongjie Li ◽

...

Keyword(s):

Venous Thromboembolism ◽

Critically Ill ◽

Critically Ill Patients ◽

Observational Studies ◽

Meta Analysis ◽

Random Effect ◽

Random Effect Model ◽

Effect Model ◽

High Prevalence ◽

Prophylactic Anticoagulation

Background: Accumulating evidence suggests that coronavirus disease 2019 (COVID-19) is associated with hypercoagulative status, particularly for critically ill patients in the intensive care unit. However, the prevalence of venous thromboembolism (VTE) in these patients under routine prophylactic anticoagulation remains unknown. A meta-analysis was performed to evaluate the prevalence of VTE in these patients by pooling the results of these observational studies.Methods: Observational studies that reported the prevalence of VTE in critically ill patients with COVID-19 were identified by searching the PubMed and Embase databases. A random-effect model was used to pool the results by incorporating the potential heterogeneity.Results: A total of 19 studies with 1,599 patients were included. The pooled results revealed that the prevalence of VTE, deep venous thrombosis (DVT), and pulmonary embolism (PE) in critically ill patients with COVID-19 was 28.4% [95% confidence interval (CI): 20.0–36.8%], 25.6% (95% CI: 17.8–33.4%), and 16.4% (95% CI: 10.1–22.7%), respectively. Limited to studies, in which all patients received routine prophylactic anticoagulation, and the prevalence for VTE, DVT, and PE was 30.1% (95% CI: 19.4–40.8%), 27.2% (95% CI: 16.5–37.9%), and 18.3% (95% CI: 9.8%−26.7%), respectively. The prevalence of DVT was higher in studies with routine screening for all patients, when compared to studies with screening only in clinically suspected patients (47.5% vs. 15.1%, P < 0.001).Conclusion: Critically ill patients with COVID-19 have a high prevalence of VTE, despite the use of present routine prophylactic anticoagulation.

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Association of FOXP3 Polymorphisms with Susceptibility to Multiple Sclerosis: A Meta-Analysis on Genetic Association Studies

Current Pharmacogenomics and Personalized Medicine ◽

10.2174/1875692118666200122163559 ◽

2020 ◽

Vol 17 (2) ◽

pp. 94-103

Author(s):

Nazanin Mousavi ◽

Seyyed Amir Yasin Ahmadi ◽

Zahra Mahmoudi ◽

Reza Nekouian ◽

Bijan Ansari-moghaddam ◽

...

Keyword(s):

Multiple Sclerosis ◽

Risk Factor ◽

Genetic Association ◽

Association Studies ◽

Meta Analysis ◽

Random Effect ◽

Random Effect Model ◽

Genetic Association Studies ◽

Genotype Frequencies ◽

Effect Model

Objectives: OXP3 is a gene related to regulatory T cells existing on chromosome X. This meta-analysis, based on genetic association studies, was conducted to investigate the association of FOXP3 polymorphisms with susceptibility to multiple sclerosis (MS). Methods: All genetic association studies covering both FOXP3 and multiple sclerosis terms were searched in PubMed, Web of Science and Google Scholar. The information of genotype frequencies was summarized and results were synthesized through odds ratio (OR). Heterogeneity and publication bias were investigated using I2 scale and Begg's funnel plot, respectively. Results: For rs3761548 -3279 C/A polymorphism, AA/AY genotypes were a risk factor in comparison to CC/CY genotypes (P =0.022; OR =1.752; 95% confidence interval [CI] =1.084-2.830; random). AC genotype was a risk factor in comparison to CC/CY genotypes (P =0.004; OR =1.537; 95% CI =1.145-2.062; random) and homozygote genotypes (P =0.016; OR =1.216; 95% CI =1.038-1.426; fixed). For rs2232365 -924 G/A polymorphism, 2 significant associations were found according to a fixed effect model; of course, they did not remain significant in the random effect model. Conclusion: According to the collected populations, susceptibility to and protection from MS are associated with rs3761548 -3279 C/A upstream polymorphism. However, it should be regarded that this association is ethnicity dependent with low effect size.

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Oral Anticoagulation after a First Episode of Venous Thromboembolism: How Long? How Strong?

Thrombosis and Haemostasis ◽

10.1055/s-0037-1615569 ◽

1999 ◽

Vol 82 (S 01) ◽

pp. 124-126 ◽

Cited By ~ 2

Author(s):

H. H. Watzke

Keyword(s):

Risk Factor ◽

Venous Thromboembolism ◽

Venous Thrombosis ◽

Short Duration ◽

Oral Anticoagulation ◽

Thrombotic Event ◽

First Episode ◽

Optimal Duration ◽

Optimal Intensity ◽

Shed Light

SummaryA number of studies have been published in the last years which shed light on the optimal intensity and the optimal duration of oral anticoagulation in patients with venous thrombosis.Based on these studies it is now generally recommended to treat patients with venous thromboembolism at an INR ranging from 2.0 to 3.0. The optimal duration of anticoagulation mainly depends on the nature of the thrombotic event. In patients with a temporary prothrombotic risk factor such as surgery, immobilization or trauma a relatively short duration of oral anticoagulation (3-6 months) is generally recommended. Patients with idiopathic venous thromboembolism require a considerably longer duration of anticoagulation (6 months at least).

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Was Antiphospholipid Syndrome a Risk Factor of Stroke? A Systemic Review and Meta-Analysis of Cohort Studies

Disease Markers ◽

10.1155/2021/4431907 ◽

2021 ◽

Vol 2021 ◽

pp. 1-9

Author(s):

Kai Zhao ◽

Ping Zhou ◽

Ling Xu ◽

Ruili Li ◽

Jincai Yang ◽

...

Keyword(s):

Risk Factor ◽

Autoimmune Diseases ◽

Cohort Studies ◽

Publication Bias ◽

Antiphospholipid Syndrome ◽

Meta Analysis ◽

Random Effect ◽

Random Effect Model ◽

Systemic Review ◽

Effect Model

Antiphospholipid syndrome (APS) is characterized by thrombosis. This systemic review and meta-analysis was to verify the hypothesis that APS might increase the risk of stroke. Studies were identified after literature searching of PubMed, Embase, and Cochrane. Newcastle-Ottawa Quality Assessment Scale Cohort Studies (NOQAS-C) was used to assess the quality of studies. The pooled effect with 95% confidence interval (95% CI) was calculated by random-effect model. I -square ( I 2 ) was used to test heterogeneity. Funnel plot was used to evaluate publication bias. A total of 17 cohort studies with overall high quality were included. There was no publication bias. Pooled hazard ratio of stroke occurrence in APS patients was 1.76 (1.39-2.21) with low heterogenicity and stable result from sensitivity analysis. In the analysis of subgroups, pooled risk ratios of stroke occurrence in patients with only positive antibodies of APS diagnosis were 1.75 (0.99-3.09), which for the APS patients with other autoimmune diseases were 14.70 (7.56-28.56). APS might be a risk factor of stroke, especially in patients with other autoimmune diseases.

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Relation Between Cigarette Smoking and Sarcopenia: Meta-Analysis

Physiological Research ◽

10.33549/physiolres.932802 ◽

2015 ◽

pp. 419-426 ◽

Cited By ~ 34

Author(s):

M. STEFFL ◽

R. W. BOHANNON ◽

M. PETR ◽

E. KOHLIKOVA ◽

I. HOLMEROVA

Keyword(s):

Risk Factor ◽

Cigarette Smoking ◽

Meta Analysis ◽

Random Effect ◽

Random Effect Model ◽

Fixed Effect Model ◽

Fixed Effect ◽

Effect Model ◽

The Individual ◽

The Relationship

Cigarette smoking is a risk factor for many diseases. It could be associated with sarcopenia. The aim of this meta-analysis was to determine whether smoking is an isolated risk factor for sarcopenia. We searched PubMed, Web of Science, EBSCO, and Science Direct for articles addressing the relationship between cigarette smoking and sarcopenia. A total of 12 studies containing information on 22,515 participants were included in this meta-analysis. Odds ratio (OR) was calculated for each study group and for all studies together. An OR was also calculated separately for each sex. We used a fixed-effect model in overall estimation and in males, because results of small studies were significantly different from the results of large studies in those cases and in females where the estimation showed only moderate heterogeneity we used a random-effect model. According to proposes of the Cochrane Handbook for Systematic Reviews. The resulting OR in the fixed-effect model was 1.12 (95 % CI 1.03-1.21), OR for each sex was in the fixed-effect model 1.20 (95 % CI 1.06-1.35) in males and in the random-effect model 1.21 (95 % CI 0.92-1.59) in females. The results of this meta-analysis indicate that cigarette smoking as an isolated factor may contribute to the development of sarcopenia. However, the results of the individual studies were largely inconsistent due to different approaches of measuring the main variables which affected the results.

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