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Circulation Jul 2015Evidence regarding the use of direct oral anticoagulants (DOACs) in the elderly, particularly bleeding risks, is unclear despite the presence of greater comorbidities,... (Meta-Analysis)
Meta-Analysis Review
Efficacy and Harms of Direct Oral Anticoagulants in the Elderly for Stroke Prevention in Atrial Fibrillation and Secondary Prevention of Venous Thromboembolism: Systematic Review and Meta-Analysis.
BACKGROUND
Evidence regarding the use of direct oral anticoagulants (DOACs) in the elderly, particularly bleeding risks, is unclear despite the presence of greater comorbidities, polypharmacy, and altered pharmacokinetics in this age group.
METHODS AND RESULTS
We performed a systematic review and meta-analysis of randomized trials of DOACs (dabigatran, apixaban, rivaroxaban, and edoxaban) for efficacy and bleeding outcomes in comparison with vitamin K antagonists (VKA) in elderly participants (aged ≥75 years) treated for acute venous thromboembolism or stroke prevention in atrial fibrillation. Nineteen studies were eligible for inclusion, but only 11 reported data specifically for elderly participants. The efficacy in managing thrombotic risks for each DOAC was similar or superior to VKA in elderly patients. A nonsignificantly higher risk of major bleeding than with VKA was observed with dabigatran 150 mg (odds ratio, 1.18; 95% confidence interval, 0.97-1.44) but not with the 110-mg dose. Significantly higher gastrointestinal bleeding risks with dabigatran 150 mg (1.78, 1.35-2.35) and dabigatran 110 mg (1.40, 1.04-1.90) and lower intracranial bleeding risks than VKA for dabigatran 150 mg (0.43, 0.26-0.72) and dabigatran 110 mg (0.36, 0.22-0.61) were also observed. A significantly lower major bleeding risk in comparison with VKA was observed for apixaban (0.63, 0.51-0.77), edoxaban 60 mg (0.81, 0.67-0.98), and 30 mg (0.46, 0.38-0.57), whereas rivaroxaban showed similar risks.
CONCLUSIONS
DOACs demonstrated at least equal efficacy to VKA in managing thrombotic risks in the elderly, but bleeding patterns were distinct. In particular, dabigatran was associated with a higher risk of gastrointestinal bleeding than VKA. Insufficient published data for apixaban, edoxaban, and rivaroxaban indicate that further work is needed to clarify the bleeding risks of these DOACs in the elderly.
SYSTEMATIC REVIEW REGISTRATION
http://www.crd.york.ac.uk/PROSPERO. Unique identifier: PROSPERO CRD42014007171/.
Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Hemorrhage; Humans; Randomized Controlled Trials as Topic; Secondary Prevention; Stroke; Venous Thromboembolism
PubMed: 25995317
DOI: 10.1161/CIRCULATIONAHA.114.013267 -
Journal of Thrombosis and Haemostasis :... 2014New direct oral anticoagulants (NOACs) constitute a novel treatment option for acute venous thromboembolism (VTE), with practical advantages. Individual studies have... (Meta-Analysis)
Meta-Analysis Review
Effectiveness and safety of novel oral anticoagulants as compared with vitamin K antagonists in the treatment of acute symptomatic venous thromboembolism: a systematic review and meta-analysis.
INTRODUCTION
New direct oral anticoagulants (NOACs) constitute a novel treatment option for acute venous thromboembolism (VTE), with practical advantages. Individual studies have demonstrated comparable efficacy to that of vitamin K antagonists (VKAs) and have suggested a more favorable safety profile . We performed a meta-analysis to determine the efficacy and safety of NOACs as compared with those of VKAs in patients with acute VTE.
METHODS
We searched MEDLINE, EMBASE, the Cochrane Database of Systematic Reviews and the Clinical Trials Registry up to October 2013. Eligible studies included phase 3 trials comparing NOACs with VKAs in patients with acute VTE. Relative risks (RRs), absolute risk differences and numbers needed to treat (NNTs) to prevent one event were calculated for recurrent VTE, fatal pulmonary embolism (PE), overall mortality, major bleeding, and other bleeding complications, with random-effects models.
RESULTS
Five studies were included, investigating four NOACs (rivaroxaban, dabigatran, apixaban, and edoxaban) in 24 455 patients with acute VTE. RRs for recurrent VTE, fatal PE and overall mortality for NOACs vs. VKAs were 0.88 (95% confidence interval [CI] 0.74-1.05), 1.02 (95% CI 0.39-5.96), and 0.97 (95% CI 0.83-1.14), respectively. The RR for major bleeding was 0.60 (95% CI 0.41-0.88). The NNT with NOACs instead of VKA to prevent one major bleed was 149. The RR and NNT for fatal bleeding were 0.36 (95% CI 0.15-0.87) and 1111. A fixed-effect network analysis did not demonstrate significant differences between individual NOACs and rivaroxaban.
CONCLUSIONS
NOACs have comparable efficacy to that of VKAs, and are associated with a significantly lower risk of bleeding complications, although the NNT to prevent one major bleed was relatively high.
Topics: Administration, Oral; Anticoagulants; Benzimidazoles; Dabigatran; Female; Hemorrhage; Humans; Male; Morpholines; Pyrazoles; Pyridines; Pyridones; Randomized Controlled Trials as Topic; Risk Factors; Rivaroxaban; Thiazoles; Thiophenes; Treatment Outcome; Venous Thromboembolism; Vitamin K; beta-Alanine
PubMed: 24330006
DOI: 10.1111/jth.12485 -
Cardiovascular Therapeutics 2022Rivaroxaban and apixaban are the most widely used nonvitamin K oral anticoagulants (NOACs) in patients with venous thromboembolism (VTE). This meta-analysis evaluates... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Rivaroxaban and apixaban are the most widely used nonvitamin K oral anticoagulants (NOACs) in patients with venous thromboembolism (VTE). This meta-analysis evaluates the effectiveness and safety of both NOACs versus standard of care (SoC) in real-world practice.
METHODS
Real-world evidence (RWE) studies were identified through a systematic literature review conducted between January 2012 and July 2020, using Embase, MEDLINE, and the websites of cardiological, hematological, and oncological associations. Eligible RWE studies recruited adult patients with deep vein thrombosis and/or pulmonary embolism and presented a comparison between rivaroxaban and apixaban versus SoC, consisting either of vitamin K antagonists, heparins, or combinations thereof. Hazard ratios (HRs) for the comparison between NOACs and SoC were extracted from the relevant studies or estimated based on the reported binary data. The between-treatment contrasts were reported as HRs with associated 95% confidence intervals.
RESULTS
A total of 65 RWE studies were identified and considered relevant for the meta-analysis. Compared with SoC, both rivaroxaban and apixaban were associated with reduced risks of recurrent VTE and a lower rate of major bleeding events. Patients treated with rivaroxaban were at a lower risk of all-cause death compared with those receiving SoC (HR = 0.56 [0.39-0.80]), while evidence for apixaban from the identified studies was insufficient to demonstrate a statistically significant change in mortality (HR = 0.66 [0.30-1.47]).
CONCLUSION
This analysis indicates that in real-world practice, rivaroxaban and apixaban are associated with a lower risk of recurrent VTE and major bleeding events compared with SoC. Survival benefit in patients treated with rivaroxaban was also observed.
Topics: Administration, Oral; Anticoagulants; Hemorrhage; Humans; Pyrazoles; Pyridones; Rivaroxaban; Treatment Outcome; Venous Thromboembolism
PubMed: 35801133
DOI: 10.1155/2022/2756682 -
Stroke Oct 2022For patients with atrial fibrillation who survive an intracranial hemorrhage (ICrH), the decision to offer oral anticoagulation (OAC) is challenging and necessitates... (Meta-Analysis)
Meta-Analysis
BACKGROUND
For patients with atrial fibrillation who survive an intracranial hemorrhage (ICrH), the decision to offer oral anticoagulation (OAC) is challenging and necessitates balancing risk of thromboembolic events with risk of recurrent ICrH.
METHODS
This systematic review assesses the effectiveness and safety of OAC and/or antiplatelets in patients with atrial fibrillation with nontraumatic ICrH. Bibliographic databases CENTRAL, MEDLINE, EMBASE, and CINAHL were searched. Articles on adults with atrial fibrillation with spontaneous ICrH (intracerebral, subdural, and subarachnoid), receiving antithrombotic therapy for stroke prevention were eligible for inclusion.
RESULTS
Twenty articles (50 470 participants) included 2 randomized controlled trials (n=304)' 8 observational studies, 8 cohort studies, and 2 studies that meta-analyzed individual-level data from observational studies. OAC therapy was associated with a significant reduction in thromboembolic events (summary relative risk [sRR], 0.51 [95% CI, 0.30-0.86], heterogeneity I=2%; =0.39, n=5 studies) and all-cause mortality (sRR, 0.52 [95% CI, 0.38-0.71], heterogeneity I=0; =0.44, n=3 studies). OAC therapy was not associated with an increased risk of recurrent ICrH (sRR, 1.44 [95% CI, 0.38-5.46], heterogeneity I=70%, =0.02, n=5 studies). Nonvitamin K antagonist OACs were more effective at reducing the risk of thromboembolic events (sRR, 0.65 [95% CI, 0.44-0.97], heterogeneity I=72%, =0.03, n=3 studies) and were associated with a lower risk of recurrent ICrH (sRR, 0.52 [95% CI, 0.40-0.67], heterogeneity I=0%, =0.43, n=3 studies) than warfarin.
CONCLUSIONS
In nontraumatic ICrH survivors with atrial fibrillation, OAC therapy is associated with a reduced risk of thromboembolic events and all-cause mortality without significantly increasing risk of recurrent ICrH. This finding is primarily based on observational data, and further larger randomized controlled trials are needed to corroborate or refute these findings.
Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Fibrinolytic Agents; Hemorrhage; Humans; Intracranial Hemorrhages; Stroke; Thromboembolism; Warfarin
PubMed: 35862238
DOI: 10.1161/STROKEAHA.122.038752 -
British Journal of Clinical Pharmacology Nov 2022The evidence of a protective effect of proton-pump inhibitor (PPI) in oral anticoagulant (OAC)-treated patients against gastrointestinal bleeding (GIB) is still lacking.... (Meta-Analysis)
Meta-Analysis Review
AIMS
The evidence of a protective effect of proton-pump inhibitor (PPI) in oral anticoagulant (OAC)-treated patients against gastrointestinal bleeding (GIB) is still lacking. We conducted a meta-analysis to estimate the risk of GIB in patients with OAC and PPI cotherapy.
METHODS
A systematic search of PubMed, EMBASE, Cochrane and Scopus databases was performed for studies reporting GIB risk in OAC and PPI cotherapy. Primary outcomes were total GIB and major GIB events. Pooled estimates of GIB risk were calculated by a random-effect meta-analysis and reported as odds ratios and 95% confidence interval.
RESULTS
A total of 10 studies and 1 970 931 patients were included. OAC and PPI cotherapy were associated with a lower odds of total and major GIB; odds ratio (95% confidence interval) was 0.67 (0.62-0.74) for total and 0.68 (0.63-0.75) for major GIB, respectively. No differences in the GIB of PPI cotherapy were observed between Asians and non-Asians (P-for-difference, total GIB = .70, major GIB = .75, respectively). For all kinds of OAC except for edoxaban, PPI cotreatment was related to lower odds of GIB by 24-44%. The protective effect of PPI on total GIB was more significant in concurrent antiplatelets or nonsteroidal anti-inflammatory drug users and those with high bleeding risks: patients with previous GIB history, HAS-BLED ≥3 or underlying gastrointestinal diseases.
CONCLUSION
In patients who receive OAC, PPI cotherapy is associated with a lower total and major GIB irrespective of ethnic group and OAC type, except for edoxaban. PPI cotherapy can be considered particularly in patients with high risk of GIB.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Anticoagulants; Gastrointestinal Hemorrhage; Humans; Proton Pump Inhibitors; Pyridines; Thiazoles
PubMed: 35921204
DOI: 10.1111/bcp.15478 -
Medicina (Kaunas, Lithuania) Oct 2023: Venous thromboembolism (VTE) is common in cancer patients. Anticoagulant therapy with low-molecular-weight heparins (LMWHs) and direct oral anticoagulants (DOACs),... (Meta-Analysis)
Meta-Analysis Review
: Venous thromboembolism (VTE) is common in cancer patients. Anticoagulant therapy with low-molecular-weight heparins (LMWHs) and direct oral anticoagulants (DOACs), such as dalteparin and apixaban, have demonstrated efficacy and safety. However, more comparative research of these drugs is still needed. This study aimed to synthesize evidence on the efficacy of apixaban compared to dalteparin in reducing recurrent VTE, major bleeding, and clinically relevant non-major bleeding associated with cancer. : We systematically searched the PubMed, Scopus, Web of Science, Embase, Cochrane Library, and ClinicalTrials databases up to 5 January 2023, for randomized controlled trials comparing apixaban versus dalteparin as treatment for cancer-associated VTE. Five studies were included. Effects according to meta-analyses were reported as relative risks (RRs) and their 95% confidence intervals (CIs). : It was found that 33 of 734 (4.5%) patients treated with apixaban and 56 of 767 (7.3%) with dalteparin had recurrent VTE as the efficacy outcome (RR 0.49, 95% CI 0.15-1.58, I 38%). Major bleeding occurred in 25 of 734 patients treated with apixaban (3.4%) and 27 of 767 with dalteparin (3.5%) (RR 1.29, 95% CI 0.31-5.27, I 59%). Likewise, clinically relevant non-major bleeding occurred in 64 of 734 patients treated with apixaban (8.7%) and 46 of 767 (5.9%) with dalteparin (RR 1.52, 95% CI 1.05-2.19, I 0%). : Apixaban showed a lower risk of recurrent VTE than dalteparin in patients with cancer-associated VTE, albeit with no statistical difference. Statistical significance was observed for no major clinically relevant bleeding but not for major bleeding.
Topics: Humans; Dalteparin; Venous Thromboembolism; Anticoagulants; Hemorrhage; Neoplasms
PubMed: 37893585
DOI: 10.3390/medicina59101867 -
Journal of Thrombosis and Haemostasis :... Jul 2017Essentials Hemorrhagic risk of antiplatelet drugs is generally thought to be lower than anticoagulants. We systematically reviewed trials comparing antiplatelet and... (Meta-Analysis)
Meta-Analysis Review
UNLABELLED
Essentials Hemorrhagic risk of antiplatelet drugs is generally thought to be lower than anticoagulants. We systematically reviewed trials comparing antiplatelet and anticoagulant drugs in older patients. Overall, the risk of major bleeding was similar with antiplatelet and with anticoagulant drugs. In elderly patients, risks and benefits of antiplatelet drugs should be carefully weighted.
SUMMARY
Background The hemorrhagic risk of antiplatelet drugs in older patients could be higher than is usually assumed. Objective To compare the bleeding risk of antiplatelet drugs and oral anticoagulants in elderly patients. Methods We carried out a systematic review and meta-analysis. We searched PubMed, EMBASE and the Cochrane Library up to January 2016 for randomized and non-randomized controlled trials (RCTs) and parallel cohorts comparing antiplatelet drugs and oral anticoagulants in patients aged 65 years or older. Two independent authors assessed studies for inclusion. The pooled relative risk (RR) of major bleeding was estimated using a random model. Results Seven RCTs (4550 patients) and four cohort studies (38 649 patients) met the inclusion criteria. The risk of major bleeding when on aspirin or clopidogrel was equal to that when on warfarin in RCTs (RR, 1.01; 95% confidence interval (95% CI), 0.69-1.48; moderate-quality evidence), lower than when on warfarin in non-randomized cohort studies (RR, 0.87; 95% CI, 0.77-0.99; low-quality evidence) and not different when all studies were combined (RR, 0.86; 95% CI, 0.73-1.01). Bleeding of any severity (RR, 0.70; 95% CI, 0.57-0.86) and intracranial bleeding (RR, 0.46; 95% CI, 0.30-0.73) were less frequent with antiplatelet drugs than with warfarin. All-cause mortality was similar (RR, 0.99). Subgroup analysis suggested that major bleeding might be higher with warfarin than with aspirin in patients over 80 years old. Conclusion Elderly patients treated with aspirin or clopidogrel suffer less any-severity bleeding but have a risk of major bleeding similar to that of oral anticoagulants, with the exception of intracranial bleeding.
Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Aspirin; Atrial Fibrillation; Clopidogrel; Cohort Studies; Female; Hemorrhage; Humans; Intracranial Hemorrhages; Male; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Risk; Stroke; Ticlopidine; Treatment Outcome; Vitamin K; Warfarin
PubMed: 28393461
DOI: 10.1111/jth.13697 -
International Journal of Surgery... Oct 2017The aim of the present study was to compare the efficacy and safety of oral tranexamic acid (TXA) with controls or intravenous TXA in patients undergoing total joint... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
The aim of the present study was to compare the efficacy and safety of oral tranexamic acid (TXA) with controls or intravenous TXA in patients undergoing total joint arthroplasty (TJA) in a systematic review and meta-analysis.
METHODS
We systematically searched randomized controlled trials (RCTs) from PubMed, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science and Google databases. Any studies comparing oral TXA versus a control group or intravenous TXA for patients prepared for TJA were included. The outcomes included the need for transfusion, hemoglobin drops, length of hospital stay and drain volume. We calculated the risk ratio (RR) with a 95% confidence interval (CI) for the need of transfusion and the weighted mean difference (WMD) with a 95% CI for hemoglobin drop, length of hospital stay and drain blood loss. Stata 12.0 was used for the meta-analysis.
RESULTS
Five clinical trials (5 RCTs) involving 333 patients were finally included in this meta-analysis. When compared with the control group, oral TXA was associated with less need for transfusion, fewer hemoglobin drops, less drain volume and a shorter length of hospital stay (P < 0.05). When compared with IV TXA, oral TXA was associated with more hemoglobin drops (P < 0.05). However, there was no significant difference between the need for transfusion, drain volume and the length of hospital stay between oral TXA and IV TXA.
CONCLUSION
Oral TXA has comparable hemostatic effects with IV TXA and may reduce the costs for patients prepared for TJA. However, considering the limited quality and number of the included studies, more high-quality and multi-center RCTs are still needed to recommend oral TXA for routine administration.
Topics: Administration, Intravenous; Administration, Oral; Aged; Antifibrinolytic Agents; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Blood Transfusion; Female; Hemostatics; Humans; Male; Middle Aged; Postoperative Hemorrhage; Randomized Controlled Trials as Topic; Tranexamic Acid; Treatment Outcome
PubMed: 28797918
DOI: 10.1016/j.ijsu.2017.08.009 -
Cureus Apr 2021Background There are no clear consensus guidelines on the indications and types of anticoagulation therapies in patients with bio-prosthetic valves either with...
Background There are no clear consensus guidelines on the indications and types of anticoagulation therapies in patients with bio-prosthetic valves either with concomitant atrial fibrillation (AF) or sinus rhythm. In our meta-analysis, we assessed the safety and efficacy of DOACs as compared to the standard treatment with warfarin in patients with AF and bioprosthetic valves. Methods We included randomized controlled trials (RCTs), cohort studies in the English language, and studies reporting patients with valvular heart disease that included bioprosthetic valvular disease. A systematic literature review using Embase, PubMed, and Web of Science was performed using the terms "Direct Acting Oral Anticoagulant," "Oral Anticoagulants," "Non-Vitamin K Antagonist Oral Anticoagulant," "Atrial Fibrillation," "Bioprosthetic Valve" for literature published prior to January 2021. Extraction of data from included studies was carried out independently by three reviewers from Covidence. We assessed the methodical rigor of the included studies using the modified Downs and Black checklist. Results Four RCTs and one observational study (n=1776) were included in our study. A random-effect model using RevMan (version 5.4; The Nordic Cochrane Centre, The Cochrane Collaboration, Copenhagen) was used for data analysis. The pooled data showed that there was a non-significant reduction in the incidence of stroke and systemic embolism in the patients taking DOACs as compared to warfarin (HR 0.69; 95% CI, 0.29, 1.67; I = 50%). The incidence of major bleeding was lower in the DOACs group; the difference was statistically significant (HR 0.42; 95% CI, 0.26, 0.67; I = 7%). The difference was not statistically significant for all-cause mortality in both groups (HR 1.24; 95% CI, 0.91, 1.67; I = 0%). Conclusion Our results showed that there was no difference in the outcomes of stroke and systemic embolism between DOACs and warfarin but there were statistically significantly lower major bleeding events. We conclude that larger clinical trials are needed to assess the true safety and efficacy of DOACs in patients with AF and bioprosthetic valves.
PubMed: 34046282
DOI: 10.7759/cureus.14651 -
International Journal of Cardiology Jun 2018Use of oral anticoagulant (OAC) therapy in atrial fibrillation (AF) is associated with an inherited risk of bleeding. Benefits and risks of OAC restarting after a major... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Use of oral anticoagulant (OAC) therapy in atrial fibrillation (AF) is associated with an inherited risk of bleeding. Benefits and risks of OAC restarting after a major bleeding are still uncertain. We aimed to assess effectiveness and safety of restarting OAC in AF patients after a major bleeding event.
METHODS
We performed a systematic review and meta-analysis of all studies reporting data about AF patients that sustained a major bleeding, reporting data on restarting or not restarting OAC therapy.
RESULTS
A total of seven studies were included, involving 5685 patients. No significant difference was found in "any stroke" occurrence between OAC restarters and non-restarters (odds ratio [OR]: 0.75, 95% confidence interval [CI]: 0.37-1.51), with a significant 46% relative risk reduction (RRR) (p < 0.00001) for "any thromboembolism" in OAC restarters, with consistent results when the index bleeding event was an intracranial or gastrointestinal bleeding. A significantly higher risk of recurrent major bleeding was seen (OR: 1.85, 95% CI: 1.48-2.30), but no difference in risk for recurrence of index event. OAC restarters had a 10.8% absolute risk reduction for all-cause death (OR: 0.38, 95% CI: 0.24-0.60); p < 0.00001). Net clinical benefit (NCB) analysis demonstrated that restarting OAC therapy after a major bleeding was significantly associated with a clinical advantage (NCB: 0.11, 95% CI: 0.09-0.14; p < 0.001).
CONCLUSIONS
Restarting OAC therapy after a major bleeding event in AF was associated with a positive clinical benefit when compared to non-restarting OAC, with a significant reduction in any thromboembolism and all-cause mortality.
Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Drug Administration Schedule; Hemorrhage; Humans; Observational Studies as Topic; Risk Factors
PubMed: 29572080
DOI: 10.1016/j.ijcard.2018.03.053