Prothrombin complex concentrate in major bleeding associated with DOACs; an updated systematic review and meta-analysis

Abstract Funding Acknowledgements Type of funding sources: None. Background The ‘Atrial Fibrillation Better Care’ (ABC) pathway has been recently proposed as a holistic approach for the comprehensive management of patients with Atrial Fibrillation (AF), standing on three main pillars: ‘A’ Avoid stroke (with Anticoagulants); ‘B’ Better symptom management; ‘C’ Cardiovascular and Comorbidity management. The ABC pathway is now recommended in several clinical guidelines, including the recent European Society of Cardiology (ESC) AF management guidelines. We performed a systematic review of the current evidence for use of the ABC pathway on clinical outcomes. Methods We performed a systematic review and meta-analysis according to PRISMA Guidelines. Pubmed and EMBASE were searched for studies reporting the prevalence of ABC pathway adherent management in AF patients, and its impact on clinical outcomes (all-cause death, cardiovascular death, stroke, and major bleeding). Metanalysis of odds ratio (OR) was performed with random-effect models; subgroup analysis and meta-regression were performed to account for heterogeneity; a CHA2DS2-VASc-stratified sensitivity analysis was also performed. Results Among 2862 records retrieved from the literature search, 8 studies were included. The pooled prevalence of ABC adherent management was 21% (95% confidence intervals (CI), 13-34%), with a high grade of heterogeneity; in a multivariable meta-regression model, adherence to each criteria of the ABC pathway explained most part of the heterogeneity (R2 = 98.9%). Patients treated according to the ABC pathway showed a lower risk of all-cause death (OR:0.42, 95%CI 0.31-0.56), cardiovascular death (OR:0.37, 95%CI 0.23-0.58), stroke (OR:0.55, 95%CI 0.37-0.82) and major bleeding (OR:0.69, 95%CI 0.51-0.94), with moderate heterogeneity. Meta-regressions showed that the increasing prevalence of diabetes mellitus, coronary artery disease, chronic heart failure and history of stroke were associated with a reduced effectiveness of the ABC pathway for all-cause and cardiovascular death; each comorbidity was able to explain a significant proportion of heterogeneity at univariate meta-regression. Conversely, longer follow-up time was associated with more effectiveness of the ABC pathway for all outcomes. Adherence to ABC pathway was associated with a progressively greater reduction of the all-cause death risk amongst patients with higher CHA2DS2-VASc scores; no difference in ABC pathway effectiveness was found across CHA2DS2-VASc strata for CV death and stroke occurrence. Conclusions Adherence to the ABC pathway was suboptimal, being adopted in 1 in every 5 patients. Adherence to the ABC pathway was associated with a reduction in the risk of major adverse outcomes. Our data supports extensive application of the ABC pathway for the management of AF. Abstract Figure.

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Abstract 14648: Gender Differences in Procedural Complications Associated With Atrial Fibrillation Catheter Ablation: A Systematic Review and Meta-analysis of 244,353 Patients

Circulation ◽

10.1161/circ.142.suppl_3.14648 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Author(s):

Martin L Campbell ◽

John Larson ◽

Talha Farid ◽

Stacy Westerman ◽

Michael S Lloyd ◽

...

Keyword(s):

Atrial Fibrillation ◽

Systematic Review ◽

Catheter Ablation ◽

Gender Gap ◽

Major Bleeding ◽

Fixed Effects ◽

Meta Analysis ◽

Vascular Complications ◽

Increased Risk ◽

Procedural Complications

Introduction: Women undergoing atrial fibrillation catheter ablation (AFCA) have higher rates of vascular complications and major bleeding. However, studies have been underpowered to detect differences in rare complications such as stroke/transient ischemic attack (TIA) and procedural mortality. Methods: We performed a systematic review of databases (PubMed, World of Science, Embase) to identify studies published since 2010 reporting AFCA complications by gender. Six complications of interest were: 1) vascular/groin complications; 2) pericardial effusion/tamponade; 3) stroke/TIA; 4) permanent phrenic nerve injury; 5) major bleeding & 6) procedural mortality. For meta-analysis, random effects models were used when heterogeneity between studies was ≥ 50% (vascular complications, major bleeding) and fixed effects models for other endpoints. Results: Of 5716 citations, 19 studies met inclusion criteria, comprising 244,353 patients undergoing AFCA, of whom 33% were women. Women were older (65.3 ± 11.2 vs. 60.4 ± 13.2 years), more likely hypertensive (60.6 vs. 55.5%) and diabetic (18.3 vs. 16.5%) and had higher CHA 2 DS 2 -VASc scores (3.0 ± 1.8 vs. 1.4 ± 1.4) (p<0.0001 for all comparisons). The rates of all 6 complications were significantly higher in women (Table). However, despite statistically significant differences, the overall incidences of major complications were very low in both genders: stroke/TIA (women 0.51 vs. men 0.39%) and procedural mortality (women 0.25 vs. men 0.18%). Conclusion: Women experience significantly higher rates of AFCA complications. However, the incidence of major procedural complications is very low in both genders. The higher rate of complications in women may be partially attributable to older age and a higher prevalence of comorbidities at the time of ablation. More detailed studies are needed to better define the mechanisms of increased risk in women and to identify strategies for closing the gender gap.

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

Circulation ◽

10.1161/circ.142.suppl_3.15090 ◽

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.

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Risk of major bleeding during extended oral anticoagulation in patients with first unprovoked venous thromboembolism: a systematic review and meta-analysis protocol

Systematic Reviews ◽

10.1186/s13643-019-1175-5 ◽

2019 ◽

Vol 8 (1) ◽

Cited By ~ 1

Author(s):

Faizan Khan ◽

Miriam Kimpton ◽

Tobias Tritschler ◽

Grégoire Le Gal ◽

Brian Hutton ◽

...

Keyword(s):

Systematic Review ◽

Venous Thromboembolism ◽

Anticoagulant Therapy ◽

Major Bleeding ◽

Oral Anticoagulation ◽

Meta Analysis ◽

Controlled Trials ◽

Bleeding Events ◽

Major Bleeding Events

Abstract Background The optimal duration of anticoagulation after a first unprovoked venous thromboembolism (VTE) remains controversial. Deciding to stop or continue anticoagulant therapy indefinitely after completing 3 to 6 months of initial treatment requires balancing the long-term risk of recurrent VTE if anticoagulation is stopped against the long-term risk of major bleeding if anticoagulation is continued. However, knowledge of the long-term risk for major bleeding events during extended anticoagulation in this patient population is limited. We plan to conduct a systematic review and meta-analysis to quantify the risk for major bleeding events during extended oral anticoagulation in patients with first unprovoked VTE. Methods Electronic databases including MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials will be systematically searched with the assistance of an information specialist (from inception to March 1, 2019) to identify randomized controlled trials and prospective cohort studies reporting major bleeding during extended oral anticoagulation in patients with first unprovoked VTE, who have completed at least 3 months of initial anticoagulant therapy. Study selection, risk of bias assessment, and data extraction will be performed independently by at least two investigators. The number of major bleeding events and person-years of follow-up will be used to calculate the rate (events per 100 person-years) with its 95% confidence interval for each study cohort, during clinically relevant time periods of extended anticoagulant therapy. Results will be pooled using random effect meta-analysis. Discussion The planned systematic review and meta-analysis will provide reliable estimates of the risk for major bleeding events during extended anticoagulation. This information will help inform patient prognosis and assist clinicians with balancing the risks and benefits of treatment to guide management of unprovoked VTE. Systematic review registration PROSPERO CRD42019128597.

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Management of direct factor Xa inhibitor–related major bleeding with prothrombin complex concentrate: a meta-analysis

Blood Advances ◽

10.1182/bloodadvances.2018024133 ◽

2019 ◽

Vol 3 (2) ◽

pp. 158-167 ◽

Cited By ~ 41

Author(s):

Siavash Piran ◽

Rasha Khatib ◽

Sam Schulman ◽

Ammar Majeed ◽

Anne Holbrook ◽

...

Keyword(s):

Major Bleeding ◽

Prothrombin Complex Concentrate ◽

Meta Analysis ◽

Case Series ◽

Factor Xa ◽

The United States ◽

Effective Management ◽

Direct Factor ◽

All Cause Mortality ◽

Fxa Inhibitor

Abstract A targeted antidote for reversal of direct factor Xa (FXa) inhibitors is now available for clinical use in the United States, but it is costly and has limited availability. In a systematic review, we evaluated the safety and effectiveness of 4-factor prothrombin complex concentrate (4F-PCC) as an alternative for managing direct FXa inhibitor–related major bleeding. A systematic literature search was conducted using Medline, Embase, and the Cochrane Register of Controlled Trials up to September 2018. No comparative studies were found. Ten case series with 340 patients who received PCC for direct FXa inhibitor–related major bleeding were included. The pooled proportion of patients with effective management of major bleeding was 0.69 (95% confidence interval [CI], 0.61-0.76) in 2 studies using the International Society on Thrombosis and Haemostasis (ISTH) criteria and 0.77 (95% CI, 0.63-0.92) in 8 studies that did not use the ISTH criteria; all-cause mortality was 0.16 (95% CI, 0.07-0.26), and thromboembolism rate was 0.04 (95% CI, 0.01-0.08). On the basis of evidence with very low certainty from single-arm case series, it is difficult to determine whether 4F-PCC in addition to cessation of direct oral FXa inhibitor is more effective than cessation of direct oral FXa inhibitor alone in patients with direct FXa inhibitor–related major bleeding.

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Prophylactic anticoagulant therapy decreases the incidence of deep vein thrombosis in patients with solid tumors: A systematic review and meta-analysis

Journal of Solid Tumors ◽

10.5430/jst.v7n1p35 ◽

2017 ◽

Vol 7 (1) ◽

pp. 35

Author(s):

Yunjiao Zhou ◽

Gong Yang ◽

Chenglei Huang

Keyword(s):

Systematic Review ◽

Deep Vein Thrombosis ◽

Solid Tumors ◽

Risk Ratio ◽

Major Bleeding ◽

Meta Analysis ◽

Bleeding Events ◽

Vein Thrombosis ◽

And Control ◽

Deep Vein

It is not well understood the efficacy and safety of primary deep vein thrombosis (DVT) prophylaxis of anticoagulants in patients with solid tumors. This systematic review and meta-analysis of randomized controlled trials (RCT) determines the relative ratio of primary DVT, survival rate and bleeding events among patients with solid tumors treated with anticoagulants or placebo. Comprehensive literature searches were conducted through the Pubmed, Ovid MEDLINE and EMBASE databases published from January 1st, 1993 to December 31st, 2015. Statistical analysis was performed by RevMan 5.0 software. For DVT events, therisk ratio in 16 trials between the prophylactic and control patients was statistically significant at 0.45 [0.36-0.58]; for major bleeding events, the risk ratio in 18 trials between the prophylactic and control patients was not statistically significant at 1.33 [0.99-1.79], while that in 15 trials with clinically relevant non-major bleeding was statistically significant at 1.83 [1.46-2.30]; the risk ratio for the mortality rate of patients with solid tumors in 16 trials was not statistically significant at 0.97 [0.93-1.02]. Inconclusion, the risk ratio in this meta-analysis showed a significantly reduced incidence of DVT with anticoagulant use. Treatment to patients who had solid tumors with prophylactic anticoagulants enhanced the incidence rate of non-major bleeding but has no significant impact on the incidence rate of major bleeding. No significant differences were found in the mortality outcomes between anticoagulant and non-anticoagulant groups.

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