Warfarin Resumption after Intracranial Hemorrhage: A Systematic Review and Meta-Analysis

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3821-3821
Author(s):  
Chatree Chai-Adisaksopha ◽  
Christopher M Hillis ◽  
Daniel M. Witt ◽  
Sam Schulman ◽  
Mark Crowther ◽  
...  
Keyword(s):  
Systematic Review ◽  
Ischemic Stroke ◽  
Board Of Directors ◽  
Intracranial Hemorrhage ◽  
Research Funding ◽  
Meta Analysis ◽  
Forest Plot ◽  
Thromboembolic Events ◽  
Advisory Committees ◽  
All Cause Mortality

Abstract Objective: To assess the effect of warfarin resumption in patients who experienced warfarin-associated intracranial hemorrhage. Study design: Systematic review and meta-analysis Data sources:We searched MEDLINE (1966 to July 2016), EMBASE (1980 to July 2016) and Cochrane Library electronic database (up to July 2016). Inclusion criteria:Studies were eligible for inclusion if (1) they were randomized controlled trials, prospective cohort or retrospective cohort studies, (2) studies that included adult patients (≥18 years), (3) studies that investigated the patients who experienced warfarin-associated intracranial bleeding, (4) studies that evaluated incidence of recurrent intracranial hemorrhage, thromboembolic events, and all-cause mortality, and (5) studies that reported on patients with warfarin resumption compared to controls (those who did not resume warfarin). Main outcome and measures: Primary outcome was all-cause mortality. Secondary outcomes were ischemic stroke, thromboembolic events, recurrent intracranial hemorrhage and any bleeding. Pooled relative risks (RRs) were calculated using random-effects model. Results: Seven studies were included in the meta-analysis, involving 623 patients who resumed warfarin and 1851 patients who did not resume warfarin after warfarin-associated intracranial hemorrhage. Majority of patients were anticoagulated due to atrial fibrillation, prosthetic heart valve and venous thrombosis. Median time to resume warfarin ranged form 11 days to 39.2 days. Warfarin resumption significantly reduced risk of all-cause mortality (17.06% vs 35.71%), RR 0.50, 95% confidence interval [CI];0.33-0.77, I-square=58.7%, Figure 1. Lower ischemic stroke was observed in patients who resumed warfarin (4.89% vs 7.64%), RR 0.67, 95%CI; 0.45-0.99, I-square=0%, Figure 2. Composite outcome of thromboembolic event was lower but not significant in patients who resumed warfarin (7.35% vs 11.48%), RR 0.61, 95%CI; 0.39-1.07, I-square=50.7%. Recurrent intracranial hemorrhage was not significantly different between patients who resumed and those who did not resume warfarin (7.33% vs 7.39%), RR 1.14, 95%CI; 0.57-2.27, I-square=51.0%, Figure 3. Any bleeding was not significantly different between 2 groups (8.23% vs 8.31%), RR 1.03, 95%CI; 0.73-1.43, I-square=50.4%. Conclusions: Major limitation of this meta-analysis included potential selection bias of the original studies, specifically, patients with better prognosis tended be selected to restart warfarin. In summary, , warfarin resumption after warfarin-associated intracranial hemorrhage was associated with lower risk of all-cause mortality and ischemic stroke without a significant increase in recurrent intracranial hemorrhage. Figure 1 Forest plot of all-cause mortality comparing patients who do and do not resume warfarin. Figure 1. Forest plot of all-cause mortality comparing patients who do and do not resume warfarin. Figure 2 Forest plot of ischemic stroke comparing between patients who do and do not resume warfarin. Figure 2. Forest plot of ischemic stroke comparing between patients who do and do not resume warfarin. Figure 3 Forest plot of recurrent intracranial hemorrhage comparing between patients who resume warfarin versus those who did not resume. Figure 3. Forest plot of recurrent intracranial hemorrhage comparing between patients who resume warfarin versus those who did not resume. Disclosures Hillis: Celgene: Consultancy; Novartis: Consultancy, Honoraria, Research Funding, Speakers Bureau; BMS: Honoraria. Crowther:AKP America: Membership on an entity's Board of Directors or advisory committees; Alexion: Consultancy, Speakers Bureau; Bayer AG: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Boehringer-Ingelheim: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb - Pfizer alliance: Honoraria; Celgene: Honoraria; CSL Behring: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Daichii: Honoraria; Leo Pharma: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Octapharma: Consultancy, Membership on an entity's Board of Directors or advisory committees; Ortho Clinical Diagnostics: Honoraria; Pfizer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Portola: Consultancy, Membership on an entity's Board of Directors or advisory committees.

scholarly journals Outcomes with Interferon in Essential Thrombocythemia: A Systematic Review and Meta-Analysis

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3147-3147
Author(s):  
Moazzam Shahzad ◽  
Mamoon Ahmed ◽  
Sakina Abbas ◽  
Muhammad Arslan ◽  
Tooba Kashif ◽  
...  
Keyword(s):  
Systematic Review ◽  
Board Of Directors ◽  
Interferon Alpha ◽  
Essential Thrombocythemia ◽  
Research Funding ◽  
Meta Analysis ◽  
Molecular Response ◽  
Publicly Traded ◽  
Advisory Committees ◽  
Hematological Response

Abstract Introduction Essential thrombocythemia (ET) is a BCR-ABL negative myeloproliferative disorder characterized by high burden of symptoms, thrombocytosis, increased risk of thrombosis and bleeding, and risk of progression to Myelofibrosis. Interferon alpha (IFN-α) is a potent immunomodulation agent proposed to be capable of inducing complete hematological remission in patients with myeloproliferative disorders. Many INF- α have been studied for treatment of patients with ET. We present a systematic review and meta-analysis assessing the efficacy of IFN-α therapy in patients with ET. Methods Following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, a comprehensive literature search was conducted on PubMed, Cochrane, and Clinical trials.gov using MeSH terms and keywords for " Thrombocythemia, Essential " AND " Interferons " in April 2021. We did not place any time constraints. Our search produced a total of 825 records and duplicates were removed. After screening and removing irrelevant and review articles, we included 21 original articles reporting IFN-α as the only treatment for ET in adult patients. The data were collected for baseline characteristics of the participants and efficacy and safety of the intervention. Quality evaluation was done using the NIH quality assessment tool. The inter-study variance was calculated using the Der Simonian-Laird Estimator. Proportions along with 95% Confidence Interval (CI) were extracted to compute pooled analysis using the 'meta' package by Schwarzer et al. in the R programming language (version 4.16-2). Results A total of 388 patients from 21 articles were evaluated. The median age of participants was 54 (35-62) years and 31% (n=64/205) were males. The type of IFN used were Interferon-alpha in 4 studies, pegylated (PEG)IFN-α-2a in 2 studies, IFN-α-2b in 6 studies, recombinant IFN-α-2C in 3 studies, recombinant IFN-y in 1 study, PEG-IFN-2b in 1 study, recombinant IFN-2b in 2 studies, and PEG-IFN in 1 study. The pooled overall hematological response (OHR) was 86.4% (95% Cl 0.67-0.98, I 2= 65%, p=0.02, n=73) with complete hematological response (CHR) of 70.6% (95% Cl 0.54-0.84, I 2=34%, p=0.21, n=65) and partial hematological response (PHR) of 13% (95% Cl 0.02-0.27, I 2=42%, p=0.16, n=65). The pooled overall molecular response (OMR) was 84% (95% Cl 0.72-0.93, I 2=13%, p=<0.01, n=81) with complete molecular response (CMR) of 64.2% (95% Cl 0.41-0.84, I 2=68%, p=<0.01, n=81) and partial molecular response (PMR) of 35% (95% Cl 0.16-0.56, I 2=33%, p=0.01, n=43). Side effects reported were nausea, allergic reactions, liver dysfunction, dose dependent mild myalgia, fever, malaise, itching, persistent fever, headache, and flu like symptoms. Conclusion Interferon alpha, in different formulations shows consistent and high activity in patients with essential thrombocythemia. It resulted in clinical responses, as well as molecular responses. Side effect profiles were consistent among different reports and were reasonable tolerated. There is a large body of evidence supporting actively and safety of this approach in a diverse ET patient population. Figure 1 Figure 1. Disclosures McGuirk: Gamida Cell: Research Funding; Juno Therapeutics: Consultancy, Honoraria, Research Funding; Magenta Therapeutics: Consultancy, Honoraria, Research Funding; Kite/ Gilead: Consultancy, Honoraria, Other: travel accommodations, expense, Kite a Gilead company, Research Funding, Speakers Bureau; Astelllas Pharma: Research Funding; Novartis: Research Funding; Allovir: Consultancy, Honoraria, Research Funding; Bellicum Pharmaceuticals: Research Funding; Fresenius Biotech: Research Funding; Novartis: Research Funding; EcoR1 Capital: Consultancy; Pluristem Therapeutics: Research Funding. Yacoub: Dynavex: Current equity holder in publicly-traded company; Cara: Current equity holder in publicly-traded company; Ardelyx: Current equity holder in publicly-traded company; Agios: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; ACCELERON PHARMA: Membership on an entity's Board of Directors or advisory committees; CTI Biopharma: Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Incyte: Consultancy, Honoraria, Speakers Bureau; Seattle Genetics: Honoraria, Speakers Bureau; Hylapharm: Current equity holder in publicly-traded company.

scholarly journals Outcomes with Interferon in Polycythemia Vera: A Systematic Review and Meta-Analysis

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3659-3659
Author(s):  
Moazzam Shahzad ◽  
Mamoon Ahmed ◽  
Muhammad Arslan ◽  
Sakina Abbas ◽  
Tooba Kashif ◽  
...  
Keyword(s):  
Systematic Review ◽  
Side Effects ◽  
Polycythemia Vera ◽  
Board Of Directors ◽  
Research Funding ◽  
Meta Analysis ◽  
Molecular Response ◽  
Publicly Traded ◽  
Advisory Committees ◽  
Hematological Response

Abstract Introduction Polycythemia Vera (PV) is a chronic myeloproliferative neoplasm that presents with increase proliferation of red cells as well as variable presence of thrombocytosis & leukocytosis. Currently treatment options for PV are phlebotomy, low-dose aspirin or cytoreductive therapy. Interferon (IFN) is a biological response modifier that exerts myelosuppressive action on excessively proliferative cell lineages and is also a non-leukemogenic drug. We conducted a systematic review and meta-analysis on the efficacy of Interferon for the treatment of PV. Methods Following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, a comprehensive literature search was conducted on PubMed, Cochrane, and Clinical trials.gov using MeSH terms and keywords for " Polycythemia Vera " AND " Interferons ". A total of 577 records were discovered using database searching. All search results were imported into the Endnote X9.0 reference manager, and duplicates were removed. After screening and excluding review and irrelevant articles, 22 original articles reporting IFN as treatment for PV in adult patients were included. The data were collected for baseline characteristics of the participants and efficacy and safety of the intervention. Quality evaluation was done using the NIH quality assessment tool. The inter-study variance was calculated using the Der Simonian-Laird Estimator. Proportions along with 95% Confidence Interval (CI) were extracted to compute pooled analysis using the 'meta' package by Schwarzer et al. in the R programming language (version 4.16-2). Results A total of 1123 patients were evaluated from 22 studies. The median age was 54.5 (47.5-67) years and median follow-up time was 24 (9-146) months. The median prior number of phlebotomies was 4.55 (2-18). The type of IFN used were recombinant IFN-alpha-2a in 2 studies, IFN-a2b in 5 studies, recombinant IFN-a in 6 studies, and Pegylated-recombinant IFN-α2a in 7 studies. The pooled overall hematological response (OHR) was 86% (95% Cl 0.76-0.93, I 2= 84%, p=<0.01, n=460) with pooled complete hematological response (CHR) of 63% (95% Cl 0.50-0.76, I 2=85%, p=<0.01, n=409) and pooled partial hematological response (PHR) of 22% (95% Cl 0.12-0.34, I 2=81%, p=<0.01, n=361). Pooled overall molecular response (OMR) was 64% (95% Cl 0.56-0.71, I 2=0%, p=0.6, n=190) with pooled complete molecular response (CMR) of 24% (95% Cl 0.14-0.35, I 2=75%, p=<0.01, n=276) and pooled partial molecular response (PMR) of 38% (95% Cl 0.31-0.45, I 2=0%, p=0.5, n=191). Side effects reported were nausea, allergic reactions, liver dysfunction, dose dependent mild myalgia, fever, malaise, itching, persistent fever, headache, and flu like symptoms [Table 1]. Conclusion Interferon shows promising results when used for the treatment of polycythemia vera with a durable hematologic and molecular response and has an acceptable side effects profile. However, large randomized clinical trials are needed to confirm these findings and to explore the dose and combination of interferon with other drugs.. Figure 1 Figure 1. Disclosures Abhyankar: Incyte/Therakos: Consultancy, Research Funding, Speakers Bureau. McGuirk: Bellicum Pharmaceuticals: Research Funding; Juno Therapeutics: Consultancy, Honoraria, Research Funding; Pluristem Therapeutics: Research Funding; Novartis: Research Funding; Allovir: Consultancy, Honoraria, Research Funding; EcoR1 Capital: Consultancy; Novartis: Research Funding; Magenta Therapeutics: Consultancy, Honoraria, Research Funding; Fresenius Biotech: Research Funding; Kite/ Gilead: Consultancy, Honoraria, Other: travel accommodations, expense, Kite a Gilead company, Research Funding, Speakers Bureau; Astelllas Pharma: Research Funding; Gamida Cell: Research Funding. Yacoub: Dynavex: Current equity holder in publicly-traded company; Cara: Current equity holder in publicly-traded company; Ardelyx: Current equity holder in publicly-traded company; Agios: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; ACCELERON PHARMA: Membership on an entity's Board of Directors or advisory committees; CTI Biopharma: Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Incyte: Consultancy, Honoraria, Speakers Bureau; Seattle Genetics: Honoraria, Speakers Bureau; Hylapharm: Current equity holder in publicly-traded company.

Systematic Review and Meta-Analysis Of Rituximab For The Treatment Of Immune Thrombocytopenia In Adults

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 1681-1681 ◽  
Author(s):  
Shaan Chugh ◽  
Donald Arnold ◽  
Wendy Lim ◽  
Mark A. Crowther ◽  
Saeed Darvish-Kazem
Keyword(s):  
Systematic Review ◽  
Platelet Count ◽  
Board Of Directors ◽  
Research Funding ◽  
Immune Thrombocytopenia ◽  
Meta Analysis ◽  
Risk Of Infection ◽  
Advisory Committees ◽  
Count Response

Abstract Background Rituximab, a monoclonal anti-CD20 antibody is commonly used to treat immune thrombocytopenia (ITP). Results of randomized controlled trials (RCTs) evaluating the efficacy of rituximab are conflicting. We conducted a systematic review and meta-analysis of RCTs to determine a more precise estimate of the effect of rituximab on platelet count response in adults with ITP. Methods We searched MEDLINE (from 1946), EMBASE (from 1980), and the Cochrane database using the MeSH terms antibodies, monoclonal, and purpura thrombocytopenia idiopathic and the textwords rituximab, rituxan, mabthera, and immune thrombocytopenic purpura. In duplicate, two reviewers independently assessed study eligibility, abstracted data and assessed each study for methodological quality. Results We identified 4 RCTs (n=360) that met our eligibility criteria. Each trial compared rituximab to placebo combined with other ITP treatments, including dexamethasone, or standard of care. Each trial enrolled non-splenectomized patients only. The likelihood of achieving a platelet count >100 x109/L at 6 months was greater with rituximab than placebo (relative risk [RR] 1.38, 95% CI 1.08-1.76). More patients receiving rituximab achieved a platelet count greater than 50 x109/L at 6 months (RR 1.46, 95% CI 1.18-1.80) compared to placebo. Rituximab was not associated with a reduction in the risk of any bleeding (RR 1.49, 95% CI 0.55-4.04) or an increase in the risk of infection (RR 1.33, 95% CI 0.74-2.38). Conclusions Rituximab is associated with a modest increase in the likelihood of achieving a platelet count greater than >100 x109/L at 6 months compared to placebo. No significant reduction in bleeding or increased risk of infection was observed at 6 months. Randomized trials were generally small, with relatively short follow-up. Large pragmatic multicenter comparative trials are needed to examine durability of response over a longer period of follow-up. Disclosures: Arnold: Amgen: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding, Speakers Bureau; GlaxoSmithKline: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding, Speakers Bureau; Hoffman-LaRoche: Research Funding. Lim:Leo Pharma: Honoraria, Research Funding; Pfizer: Consultancy, Honoraria. Crowther:Asahi Kasai: Membership on an entity’s Board of Directors or advisory committees; Baxter: Membership on an entity’s Board of Directors or advisory committees, Speakers Bureau; Boehringer Ingelheim: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees; CSL Behring: Speakers Bureau; Leo Pharma: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding, Speakers Bureau; Merck: Consultancy; Octapharma: Consultancy, Membership on an entity’s Board of Directors or advisory committees; Pfizer: Consultancy, Honoraria, Research Funding; Sanofi-Aventis: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding; Viropharma: Membership on an entity’s Board of Directors or advisory committees.

scholarly journals Inherited Thrombophilia and the Risk of Arterial Ischemic Stroke: A Systematic Review and Meta-Analysis

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2518-2518
Author(s):  
Thita Chiasakul ◽  
Elizabeth De Jesus ◽  
Jiayi Tong ◽  
Yong Chen ◽  
Mark Crowther ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Board Of Directors ◽  
Research Funding ◽  
Meta Analysis ◽  
Cryptogenic Stroke ◽  
Young Patients ◽  
Case Control Studies ◽  
Arterial Ischemic Stroke ◽  
Advisory Committees ◽  
Inherited Thrombophilia

Abstract Introduction:The inherited thrombophilias Factor V Leiden (FVL), the Prothrombin G20210A mutation (PTM), Protein C deficiency (PCD), Protein S deficiency (PSD), and Antithrombin deficiency (ATD) are well-established predisposing factors for venous thromboembolism, but their role in arterial thrombosis such as arterial ischemic stroke remains uncertain. The 2018 American Heart Association/American Stroke Association clinical practice guideline recommends against thrombophilia testing in patients with ischemic stroke, though such testing remains common in clinical practice. We conducted a systematic review and meta-analysis to evaluate the association of inherited thrombophilias and risk of arterial ischemic stroke in adults. Methods:A systematic literature search was performed using MEDLINE, EMBASE, and Cochrane Library Databases from inception to December 31, 2017 without language restrictions. Manual reviews of conference abstracts and bibliographies of included studies were performed to identify additional eligible studies. We included case-control studies of adults age ≥15 years that reported the prevalence of at least one of the inherited thrombophilias of interest (FVL, PTM, PCD, PSD, ATD) in both subjects with a history of arterial ischemic stroke (cases) and subjects without arterial ischemic stroke (controls). Studies were required to have ≥10 subjects in each group. Studies that enrolled patients with transient ischemic attack, hemorrhagic stroke, cerebral venous sinus thrombosis, and other arterial thromboses were excluded. Two reviewers (T.C. and E.D.) independently searched the literature and extracted data from eligible studies. Disagreements were resolved by consensus or a third reviewer (A.C.) when necessary. Methodological quality of included studies was appraised using the NIH Quality Assessment of Case-Control Studies assessment tool. Data analysis was performed using R version 3.4.4. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using a random-effects model. Inter-study heterogeneity was evaluated using Cochran's Q test and I2statistics. Prespecified subgroup analyses were performed in young patients (<65 years), patients with a patent foramen ovale (PFO), and patients with cryptogenic stroke. Funnel plots and Egger's test were used to assess for the presence of publication bias. The study protocol is available on PROSPERO (CRD42018090020). Results:A total of 1,730 records were retrieved from the literature search. After screening by title and abstract, 1527 records were excluded. The remaining 203 references underwent full text review, 71 of which met eligibility criteria and were included in the analysis. These 71 studies collectively enrolled 13,347 stroke patients and 31,676 controls. The number of studies that reported on FVL, PTM, PCD, PSD, and ATD were 59, 47, 14, 15, and 11, respectively. Heterogeneity among studies was low. Compared with controls, inherited thrombophilia was significantly more common in patients with arterial ischemic stroke for the following defects: homozygous FVL (OR 2.24; 95%CI, 1.24-4.07; I2=0%), heterozygous FVL (OR 1.32; 95%CI, 1.11-1.57; I2=33%), homozygous PTM (OR 7.19; 95%CI 2.47-20.95; I2=0%), heterozygous PTM (OR 1.53; 95%CI, 1.27-1.84; I2=2%), PCD (OR 2.70; 95%CI, 1.44-5.04; I2=0%), and PSD (OR 2.75; 95%CI, 1.56-4.85; I2=34%) (Figure 1). Statistical significance was not reached for ATD (OR 1.84; 95%CI, 0.92-3.71; I2=11%). Subgroup analyses showed a higher magnitude of stroke risk in young patients across all thrombophilias. The associations were non-significant for patients with PFO and cryptogenic stroke (Table 1). Funnel plots were symmetrical and Egger's test was non-significant (p>0.05), suggesting absence of publication bias, for all thrombophilias except heterozygous FVL (p=0.003). Conclusions: Our results suggest that inherited thrombophilias including FVL, PTM, PCD, and PSD are associated with an increased risk of arterial ischemic stroke, particularly in young patients. The association with FVL and PTM is stronger in the homozygous than in the heterozygous state, suggesting a potential dose-response relationship and causal role for inherited thrombophilias. The implications of these findings with respect to the evaluation and management of patients with ischemic stroke require further investigation. Disclosures Crowther: Alnylam: Equity Ownership; Daiichi Sankyo: Membership on an entity's Board of Directors or advisory committees; Shinogi: Consultancy; Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Leo Pharma: Research Funding; Octapharma: Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria; Bayer: Membership on an entity's Board of Directors or advisory committees, Research Funding; Alexion: Speakers Bureau. Garcia:Bristol Meyers Squibb: Consultancy; Daiichi Sankyo: Research Funding; Janssen: Consultancy, Research Funding; Pfizer: Consultancy; Portola: Research Funding; Incyte: Research Funding; Retham Technologies LLC: Consultancy; Shingoi: Consultancy; Boehringer Ingelheim: Consultancy. Cuker:Kedrion: Membership on an entity's Board of Directors or advisory committees; Spark Therapeutics: Research Funding; Synergy: Consultancy; Genzyme: Consultancy.

Abstract 309: Is Right Bundle Branch Block Associated with Poor Outcomes in the Setting of an Acute Coronary Syndrome? A Systematic Review and Meta-analysis

2014 ◽  
Vol 7 (suppl_1) ◽  
Author(s):  
Ahmad Hazem ◽  
Sunita Sharma ◽  
Amit Sharma ◽  
Cameron Leitch ◽  
Roopalakshmi Sharadanant ◽  
...  
Keyword(s):  
Systematic Review ◽  
Acute Coronary Syndrome ◽  
Right Bundle Branch Block ◽  
Risk Ratio ◽  
Meta Analysis ◽  
Forest Plot ◽  
Bundle Branch Block ◽  
Coronary Syndrome ◽  
All Cause Mortality

Importance: Up to 10% of patients with acute myocardial infarction (AMI) have right bundle branch block (RBBB), and RBBB has been associated with a higher risk of mortality. We performed a systematic review and meta-analysis to determine the prognostic significance of RBBB for patients with AMI. Acute coronary syndrome (ACS) Data Sources: We have systematically searched Ovid, Scopus and Web of Science through January 2014. Study Selection: Reviewers working independently and in duplicate screened all eligible abstracts, selecting studies that described all-cause mortality or cardiovascular death in patients with RBBB and suspected ACS. We excluded studies that reported unadjusted outcomes. Knowledge synthesis: We pooled risk ratio with hazard ratio in studies reporting those outcomes. When reported, odds ratio was converted into risk ratio using reported event rate in each study’s unexposed -read: non RBBB- group. Main Outcomes: All-cause mortality and cardiovascular mortality (death). Results: Eighteen studies were found that reported eligible data. All were observational studies, involving over 89,000 patients. In short-term follow up (up to 30 days), RBBB on presentation was associated with higher all-cause mortality rate, compared to patients without RBBB (RR 2.23, 95% CI 1.76-2.82). There was a trend for higher mortality at long-term follow up (range: 6 months-16 years) that did not reach statistical significance (RR 1.45, 95% CI 0.93-2.25). Figure-1 demonstrates the forest plot. Risk of bias was assessed with the Newcastle-Ottawa scale and majority of included studied were deemed moderate to high quality. Conclusion and Relevance: RBBB is associated with a more than 2-fold higher risk of all-cause mortality in patients with AMI at 30 days follow up. Patients with AMI and RBBB represent a high risk group for adverse outcomes. A sentence on the differential findings for new vs. old RBBB and association with outcomes could follow here.

Abstract WMP112: Cilostazol versus Aspirin for Secondary Stroke Prevention: Systematic Review and Meta-Analysis

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Michelle P Lin ◽  
Kevin M Barrett ◽  
James F Meschia ◽  
Benjamin H Eidelman ◽  
Josephine F Huang ◽  
...  
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Ischemic Stroke ◽  
Random Effects ◽  
Intracranial Hemorrhage ◽  
Stroke Prevention ◽  
Lower Risk ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Secondary Stroke Prevention

Introduction: Cilostazol has promise as an alternative to aspirin for secondary stroke prevention given its vasodilatory and anti-inflammatory properties in addition to platelet aggregation inhibition. We conducted a systematic review and meta-analysis to estimate the comparative effectiveness and safety of cilostazol compared to aspirin for stroke prevention in patients with previous stroke or TIA. Hypothesis: Cilostazol is more effective than aspirin in preventing recurrent ischemic stroke with lower risk of intracranial hemorrhage and bleeding. Methods: We searched PubMed and the Cochrane Central Register of Controlled Trials from inception to 2019. Randomized clinical trials that compared cilostazol vs aspirin and reported the endpoints of ischemic stroke, intracranial hemorrhage and bleeding were included. A random-effects estimate was computed based on Mantel-Haenszel methods. The pooled estimates with 95% confidence intervals were compared between cilostazol and aspirin and displayed as forest plots (Figure). Results: The search identified 5 randomized clinical trials comparing cilostazol vs aspirin for secondary stroke prevention that enrolled 7,240 patients from primarily Asian countries (3,615 received cilostazol and 3,625 received aspirin). The pooled results from the random-effects model showed that cilostazol was associated with significantly lower risk of recurrent ischemic stroke (Hazard ratio [HR] 0.70; 95%CI, 0.54-0.89), intracranial hemorrhage (HR 0.41; 95%CI, 0.25-0.65) and bleeding (HR 0.71; 95%CI, 0.55-0.91). See forest plots. Conclusion: This meta-analysis suggests cilostazol is more effective than aspirin in the prevention of recurrent ischemic stroke with lower risk of intracranial hemorrhage and bleeding. Confirmatory randomized trials of cilostazol for secondary stroke prevention to be performed in more generalizable populations are needed.

Abstract 15090: Direct Oral Anticoagulation vs Vitamin K Antagonist in Atrial Fibrillation With Liver Disease: A Systematic Review and Meta-analysis

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Mahmoud El Iskandarani ◽  
Islam Shatla ◽  
Muhammad Khalid ◽  
Bara El Kurdi ◽  
Timir Paul ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Systematic Review ◽  
Ischemic Stroke ◽  
Liver Disease ◽  
Vitamin K ◽  
Major Bleeding ◽  
Lower Risk ◽  
Meta Analysis ◽  
Vitamin K Antagonist ◽  
All Cause Mortality

Background: Current guidelines recommend against the use of direct oral anticoagulation (DOAC) therapy in patients with atrial fibrillation (AF) in the setting of significant liver disease (LD) due to lack of evidence in safety and efficacy studies. However, recently studies have investigated the role of DOAC in comparison to Vitamin K antagonist (VKA) in this category of patients. Therefore, we conducted a systematic review and meta-analysis to evaluate the efficacy and safety of this approach. Hypothesis: DOAC is safe and effective compared to VKA in AF with LD patients. Method: Unrestricted search of the PubMed, EMBASE, and Cochrane databases performed from inception until June 1, 2020 for studies comparing DOAC with VKA including more than 100 AF patients with LD. Relevant data were extracted and analyzed using Revman 5.3 software. Hazard ratio (HR) and 95% Confidence interval (CI) were calculated using the random-effects model. Result: A total of 5 studies (3 retrospective and 2 post hoc analysis) were included examining 39,064 patients with AF and LD (25,398 DOAC vs 13,669 VKA). DOAC is associated with lower risk of major bleeding compared to VKA with a HR of 0.68 (95% CI 0.47-0.98; I 2 =53%), all-cause mortality (HR 0.74;95% CI 0.59-0.94; I 2 =61%), and intracranial bleeding (HR 0.48; 95% CI 0.40-0.58; I 2 =0). There was no significant difference in ischemic stroke risk (HR 0.73; 95% CI 0.47-1.14; I 2 =72%) and gastrointestinal bleeding risk (0.96; 95% CI 0.61-1.51; I 2 =41%) between DOAC and VKA. Conclusion: DOAC is non-inferior to VKA regarding ischemic stroke prevention in AF patients with LD. Moreover, DOAC is associated with a lower risk of major bleeding, intracranial bleeding and all-cause mortality. Further randomized trials are needed to validate our findings.

The Ultra-Low-Molecular-Weight Heparin Semuloparin for Prevention of Venous Thromboembolism In Patients Undergoing Major Abdominal Surgery

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 188-188 ◽  
Author(s):  
Ajay K. Kakkar ◽  
Giancarlo Agnelli ◽  
William D. Fisher ◽  
Daniel George ◽  
Patrick Mouret ◽  
...  
Keyword(s):  
Abdominal Surgery ◽  
Board Of Directors ◽  
Research Funding ◽  
Major Abdominal Surgery ◽  
Low Molecular Weight ◽  
Primary Efficacy ◽  
Advisory Committees ◽  
Once Daily ◽  
All Cause Mortality ◽  
Bayer Healthcare

Abstract Abstract 188 Background/Aim: Venous thromboembolism (VTE) remains a common and potentially fatal complication of major abdominal surgery. Semuloparin is a novel ultra-low-molecular-weight heparin (ULMWH) with high anti-factor Xa and residual anti-factor IIa activities currently under development for prevention of VTE. We have conducted a study to assess the efficacy and safety of semuloparin compared to enoxaparin for the prevention of VTE in patients undergoing major abdominal surgery. Material and methods: SAVE-ABDO is a multinational, randomized, double-blind phase III study of patients undergoing major abdominal or pelvic operation. Patients were randomized to receive either once-daily enoxaparin 40 mg commenced pre-operatively or semuloparin 20 mg commenced post-operatively, both agents continued for 7–10 days. Patients were eligible for inclusion if they were aged > 60 years, had undergone major surgery in the peritoneal or the retroperitoneal space, and/or pelvis under general anesthesia lasting more than 45 minutes. For patients under the age of 60 years old, an additional risk factor (history of VTE, body mass index ≥ 30 kg/m2, chronic heart failure, chronic respiratory failure, inflammatory bowel disease, or operation for malignancy) was required. For patients with severe renal impairment, defined as a creatinine clearance < 30 mL/min, the dose of semuloparin was reduced to 10 mg once-daily, and that of enoxaparin to 20 mg once-daily. Randomization was stratified by indication for operation (cancer versus non-cancer), renal function (creatinine clearance ≥ or < 30 mL/min), and geographic region. Mandatory bilateral venography was performed between day 7 and 11. The primary efficacy endpoint was the composite of any deep vein thrombosis (DVT), non-fatal pulmonary embolism (PE), and all-cause mortality. Secondary efficacy endpoints included the composite of any VTE and VTE-related mortality, and the composite of any proximal DVT, symptomatic distal DVT, non-fatal pulmonary embolism, and all-cause mortality. The main safety endpoint was major bleeding, with main secondary safety endpoints of clinically-relevant non-major (CRNM) bleeding, and the composite of major and CRNM bleeding. All study endpoints were independently and blinded adjudicated. The non-inferiority will be reached if the upper limit of the confidence interval of the odds ratio for the primary analysis is < 1.25. If the non-inferiority is demonstrated the superiority will be tested using a stratified exact test on the primary efficacy endpoint. Results: 4414 patients were randomized between May 2008 and June 2010. The mean age was 61 years (±13 years) and 57% of subjects were male. 81% of patients underwent an operation for malignant disease. The majority of patients underwent gastro-intestinal procedures, with 59% having colon or colo-rectal surgery, and 20% gastric surgery. Final data will be available for presentation at the meeting. Disclosures: Kakkar: Bayer Healthcare: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; sanofi-aventis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Boehringer-Ingelheim: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol-Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Eisai: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Agnelli:sanofi-aventis: Research Funding. Fisher:sanofi-aventis: Honoraria, Research Funding; Bayer Healthcare: Honoraria, Research Funding; Takeda Pharmaceuticals: Honoraria, Research Funding; Pfizer: Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Boehringer-Ingelheim: Membership on an entity's Board of Directors or advisory committees. George:sanofi-aventis: Honoraria. Mouret:Bayer Healthcare: Consultancy, Honoraria; sanofi-aventis: Consultancy, Honoraria; Bristol-Myers Squibb: Consultancy, Honoraria. Lassen:Astellas Pharma Europe: Consultancy; Bayer Healthcare: Consultancy; Bristol-Myers Squibb: Consultancy; GlaxoSmithKline: Consultancy; Merck Serono: Consultancy; Pfizer: Consultancy; sanofi-aventis: Consultancy. Mismetti:sanofi-aventis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bayer Healthcare: Honoraria; Boehringer-Ingelheim: Honoraria; Pfizer: Honoraria; Bristol-Myers Squibb: Honoraria. Murphy:sanofi-aventis: Employment. Turpie:Astellas Pharma Europe: Consultancy; Bayer Healthcare: Consultancy; Portola Pharma: Consultancy; sanofi-aventis: Consultancy.

Low Molecular Weight Heparin for Prevention of Placenta-Mediated Pregnancy Complications: An Individual Patient Data Meta-Analysis

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 890-890
Author(s):  
Marc Rodger ◽  
Johanna IP de Vries ◽  
Evelyne Rey ◽  
Jean-Christophe JCG Gris ◽  
Ida Martinelli ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Research Funding ◽  
Low Molecular Weight Heparin ◽  
Individual Patient Data ◽  
Meta Analysis ◽  
Risk Difference ◽  
Patient Data ◽  
Low Molecular Weight ◽  
Single Center ◽  
Advisory Committees

Abstract Introduction Placenta-mediated pregnancy complications (PMPC) include pre-eclampsia, late pregnancy loss, placental abruption, and the small-for-gestational age (SGA) newborn. They are leading causes of maternal, fetal, and neonatal morbidity and mortality. Affected women are at an elevated risk of recurrence in subsequent pregnancies. We completed a pooled summary-based (i.e. study level) meta-analysis that strongly suggests that low-molecular-weight heparin (LMWH) reduces the risk of recurrent PMPCs. However, our study-level meta-analysis was limited by high clinical and statistical heterogeneity likely due to the inclusion of women with heterogeneous prior PMPCs and trial designs (e.g. single vs multi-center trials). To address these limitations, the trialists agreed to conduct an individual patient data meta-analysis to identify sources of heterogeneity including exploring which patients benefit from LMWH and which outcomes are prevented. Methods We conducted a systematic review to identify randomised controlled trials that were eligible to contribute individual patient data to a meta-analysis to evaluate the effectiveness of LMWH for reducing the risk of PMPC in women with prior PMPCs. The primary outcome was a composite of early-onset or severe pre-eclampsia, birth of an SGA newborn < 5th percentile, late pregnancy loss (> 20 weeks), or placental abruption leading to delivery. Individual patient data from eligible women were re-coded in a prescribed format and combined in a common dataset for analysis. All studies were assessed for risk of bias. Results Data from 1049 women in nine trials were analysed; Participants were mostly Caucasian (88%) with a mean age of 31.518 had thrombophilia. 525 women were randomised to LMWH and 524 to no LMWH. In our primary outcome analysis, LMWH did not significantly reduce the risk of recurrent PMPCs (LMWH 60/459 (13.1%) vs. no LMWH 92/449 (20.5%) p=0.1). Significant heterogeneity was noted between single center and multi-center trials. In multi-center trials, LMWH reduced HELLP (p=0.03) but none of the other secondary outcomes, whereas in single center trials LMWH reduced all of the secondary outcomes. In sub-group analysis, in multi-center trials LMWH reduced the primary outcome in women with prior abruption (p<0.01) but none of the other sub-groups, whereas in single center trials LMWH was beneficial in all the sub-groups (prior pre-eclampsia, prior severe pre-eclampsia, prior early onset pre-eclampsia, prior SGA <10th, prior SGA < 5th and prior abruption). Conclusions In this individual patient data meta-analysis, LMWH does not appear to reduce the risk of recurrent PMPC in women with prior PMPC. Promising results suggest that women with prior abruption may benefit from LMWH but this should be replicated in future multi-center trials. PROSPERO registration:CRD42013006249 Table. Primary Analysis All Studies Multi-Center Studies Single Center Studies Composite outcome Risk difference (95% CI) N=908 -0.07 (-0.16, 0.01)p = 0.10 N=524 -0.01 (-0.11, 0.09) p = 0.89 N=384 -0.17 (-0.21, -0.13) p < .0001 Secondary Outcome Analyses Severe or Early Preeclampsia Risk difference (95% CI) N=946 -0.04 (-0.10, 0.02) p = 0.20 N=562 0.01 (-0.06, 0.07) p = 0.81 N=384 -0.11 (-0.16, -0.07) p <.0001 HELLP Risk difference (95% CI) N=813 -0.02 (-0.04, -0.004) p = 0.01 N=429 -0.01 (-0.02, -0.001) p = 0.03 N=384 -0.04 (-0.07, -0.01) p = 0.02 SGA <10 Risk difference (95% CI) N=913 -0.08 (-0.14, -0.02) p = 0.01 N=529 -0.03 (-0.10, 0.03) p = 0.32 N=384 -0.14 (-0.18, -0.10) p <0.0001 Abruption leading to delivery Risk difference (95% CI) N=945 -0.01 (-0.02, 0.003) p = 0.14 N=561 -0.01 (-0.03, 0.01) p = 0.53 N=384 -0.016 (-0.027, -0.005) p = 0.005 Subgroup Analyses Prior preeclampsia Risk difference (95% CI) N=583 -0.12 (-0.19, -0.04) p = 0.002 N=288 -0.06 (-0.19, 0.06) p = 0.34 N=295 -0.17 (-0.24, -0.11) p <.0001 Prior severe or early onset Preeclampsia Risk difference (95% CI) N=487 -0.10 (-0.19, -0.02) p = 0.02 N=236 -0.04 (-0.19, 0.12) p = 0.65 N=251 -0.17 (-0.23, -0.11) p <.0001 Any prior late loss (2 >12 weeks or 1 >16 weeks) Risk difference (95% CI) N=245 0.001 (-0.11, 0.12) p = 0.98 N=0 Prior SGA < 10 Risk difference (95% CI) N=305 -0.12 (-0.25, 0.01) p = 0.08 N=203 -0.03 (-0.17, 0.10) p = 0.64 N=102 -0.29 (-0.38, -0.20) p <.0001 Prior abruption Risk difference (95% CI) N=281 -0.16 (-0.22, -0.11) p <.0001 N=95 -0.13 (-0.22, -0.04) p = 0.01 N=186 -0.18 (-0.22, -0.14) p <.0001 Disclosures Rodger: Biomerieux: Honoraria, Research Funding. Off Label Use: Low Molecular Weight Heparin to prevent pregnancy complications. de Vries:Pfizer: Research Funding. Rey:Leo Pharma: Other: Travel Grant. Gris:Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Stago: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Leo Pharma: Consultancy, Speakers Bureau; LFB: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Baxter: Research Funding; BI: Speakers Bureau; Bayer: Speakers Bureau; BMS: Speakers Bureau. Schleussner:Bayer: Speakers Bureau; Pfizer: Research Funding, Speakers Bureau; Merck: Research Funding, Speakers Bureau. Middeldorp:GSK/Aspen: Research Funding; Bayer: Consultancy, Speakers Bureau; BI: Consultancy, Speakers Bureau; BMS: Consultancy, Research Funding, Speakers Bureau; Pfizer: Consultancy, Research Funding, Speakers Bureau; Daiichi-Sankyo: Consultancy, Speakers Bureau. Bates:Eli Lilly Canada: Other: I hold the Eli Lilly Canada/May Cohen Chair in Women's Health. Eli Lilly Canada provides unrestricted funding for partial salary support through this Chair. Eli Lilly Canada does not manufacture/distribute drugs relevant to the topic to be discussed..

Sign in / Sign up

Export Citation Format

Share Document