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British Journal of Clinical Pharmacology Feb 2022The results of associations between new oral anticoagulants (NOACs) and wound complications after total joint arthroplasty remain inconsistent. We conducted a systematic... (Meta-Analysis)
Meta-Analysis Review
Wound complications and bleeding with new oral anticoagulants in patients undergoing total joint arthroplasty: A systematic review and meta-analysis of randomized controlled trials.
AIMS
The results of associations between new oral anticoagulants (NOACs) and wound complications after total joint arthroplasty remain inconsistent. We conducted a systematic review and meta-analysis of randomized controlled trials to make comparisons with low molecular weight heparins (LMWH) on the clinical outcomes of total wound complications, together with other efficacy and safety endpoints to further evaluate the safety and efficacy of NOACs.
METHODS
This meta-analysis was conducted based on a published protocol (PROSPERO: CRD42019140841). We searched for available articles in PubMed, Embase and Cochrane Library through Jun 62 021. Random-effects meta-analyses, including subgroup analyses, were conducted to estimate the pooled relative risk (RR) and 95% confidence interval (CI) for specific doses of NOACs.
RESULTS
We retrieved 1683 studies, of which 20 were eligible for inclusion. We found that apixaban was associated with a lower incidence of total wound complications compared with LMWH (RR = 0.81; 95% CI: 0.65-1.00), while dabigatran and rivaroxaban did not increase the risk of total wound complications. In addition, apixaban was associated with a reduction in the risk of major/clinically relevant nonmajor bleeding events compared to LMWH (RR = 0.80, 95% CI: 0.65-0.99), while rivaroxaban increased the risk for major/clinically relevant nonmajor bleeding events (RR = 1.23, 95% CI: 1.02-1.50). Moreover, all 4 NOACs were associated with lower incidences of major venous thromboembolism compared with LMWH.
CONCLUSION
A lower risk of wound complications was detected for apixaban, while dabigatran and rivaroxaban did not increase the risk when compared with LMWH. The efficacy of 4 NOACs was broadly similar.
Topics: Administration, Oral; Anticoagulants; Arthroplasty; Dabigatran; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Randomized Controlled Trials as Topic; Rivaroxaban; Venous Thromboembolism
PubMed: 34322914
DOI: 10.1111/bcp.15005 -
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 -
Journal of Thrombosis and Haemostasis :... Sep 2022Obesity is a global epidemic and bariatric surgery is used with increasing frequency to treat its complications. The extent to which bariatric surgery alters the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Obesity is a global epidemic and bariatric surgery is used with increasing frequency to treat its complications. The extent to which bariatric surgery alters the efficacy, safety, and pharmacokinetics of direct oral anticoagulants (DOACs) is unknown.
AIMS
In this review, we summarize the evidence supporting the use of DOACs after bariatric surgery and apply our findings to resolve several clinical cases.
MATERIALS & METHODS
We systematically searched MEDLINE, EMBASE, Cochrane Library, CINAHL and ClinicalTrials.gov from January 1, 2000, to June 15, 2021 for randomized and non-randomized studies evaluating the use of DOACs for any indication after bariatric surgery. Two reviewers independently screened titles, abstracts, and full-text articles. Clinical and pharmacokinetic outcomes were pooled by random-effects meta-analysis with inverse variance weighting. We used the Newcastle-Ottawa scale to assess risk of bias in non-randomized studies and assessed the certainty of evidence with GRADE.
RESULTS
From 2519 records, we included 28 studies (n = 3229 patients): no randomized trials, 7 cohort studies, 6 case series, and 15 case reports. Incidence rates for arterial thromboembolism, venous thromboembolism and major bleeding were: 0.73 (95% confidence interval [CI]: 0.01-5.10), 2.45 (95% CI: 0.40-7.94), and 3.40 (95% CI: 0.80-9.36) events per 100 patient-years, respectively. The pooled proportion of peak direct oral anticoagulant drug levels within the expected range was 58% (95% CI: 39%-74%).
CONCLUSION
There appears be substantial risk of DOAC malabsorption after bariatric surgery that could affect clinical outcomes, however the certainty of evidence was very low.
PROSPERO
CRD42020202636.
Topics: Administration, Oral; Anticoagulants; Bariatric Surgery; Hemorrhage; Humans; Venous Thromboembolism
PubMed: 35844166
DOI: 10.1111/jth.15823 -
BMC Oral Health Oct 2023Direct oral anticoagulants (DOACs) were developed to overcome the drawbacks of oral anticoagulants. However, not much has been discussed about the perioperative...
BACKGROUND
Direct oral anticoagulants (DOACs) were developed to overcome the drawbacks of oral anticoagulants. However, not much has been discussed about the perioperative management of patients on DOACs during oral surgical procedures. Thus, we aim to determine the risk of perioperative and postoperative bleeding during oral surgical procedures in patients on DOACs.
METHODS
A detailed literature search was performed to find potentially relevant studies using the Cochrane Library, Clinical Key, ClinicalTrials.gov, Google Scholar, Ovid, ScienceDirect, and Scopus. Every article available for free in English literature for the past 10 years, between 2012 and 2022, was searched.
RESULTS
A total of 2792 abstracts were selected through a search strategy across various search engines. Based on inclusion and exclusion criteria, eleven clinical studies using DOACs as anticoagulants or studies comparing patients with and without DOACs under oral surgery procedures were found. The results were inconsistent and varied, with a few studies recommending DOAC administration with the bare minimum reported complications and others finding no statistically significant difference between discontinuation or continuation of drugs, especially across basic dental procedures.
CONCLUSION
Within the limitations of the study, it can be concluded that minor oral surgical procedures are safe for patients on DOAC therapy. However, the continuation or discontinuation of DOACs in patients undergoing oral surgical procedures remains controversial and requires further studies to extrapolate the results.
Topics: Humans; Anticoagulants; Postoperative Hemorrhage; Oral Surgical Procedures; Administration, Oral
PubMed: 37821865
DOI: 10.1186/s12903-023-03427-8 -
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 Clinical Medicine Jun 2020Adults with congenital heart disease (ACHD) experience more thromboembolic complications than the general population. We systematically searched and critically appraised... (Review)
Review
Adults with congenital heart disease (ACHD) experience more thromboembolic complications than the general population. We systematically searched and critically appraised all studies on the safety and efficacy of non-vitamin-K oral anticoagulants (NOACs) in adult patients with various forms of congenital heart disease. PubMed and the Cochrane Central Register of Controlled Trials (CENTRAL) were used, with duplicate extraction of data and risk of bias assessment. The Newcastle-Ottawa quality assessment scale was used to assess study quality. Three studies fulfilled the inclusion criteria and were analyzed. The total number of participants was 766, with a total follow-up of 923 patient-years. The majority of patients (77%) received a NOAC for atrial arrhythmias, while the remainder were prescribed NOACs for secondary (19%) or primary (4%) thromboprophylaxis. The annual rate of thromboembolic and major bleeding events was low: 0.98% (95% CI: 0.51-1.86) and 1.74% (95% CI: 0.86-3.49) respectively. In Fontan patients, the annual rate of thromboembolic and major bleeding events was 3.13% (95% CI: 1.18-8.03) and 3.17% (95% CI: 0.15-41.39) respectively. NOACs appear safe and effective in ACHD without mechanical prostheses. Additional studies are, however, needed to confirm their efficacy in complex ACHD, especially those with a Fontan-type circulation.
PubMed: 32526897
DOI: 10.3390/jcm9061794 -
Canadian Journal of Gastroenterology &... 2019Anticoagulants carry a significant risk of gastrointestinal bleeding. With the increase in use and availability of direct oral anticoagulants ("DOACs") more data are...
BACKGROUND
Anticoagulants carry a significant risk of gastrointestinal bleeding. With the increase in use and availability of direct oral anticoagulants ("DOACs") more data are available regarding the risks of these medications. With diverticular bleeds being common, and hospitalization associated with gastrointestinal bleed increasing 30-day mortality, it is paramount to better understand the potential risks of using DOACs in this population.
METHODS
A systematic review of the literature was undertaken, using the databases PubMed, EMBASE, Cochrane Library, and CINAHL. Two reviewers independently searched the literature, and initial screening was performed through title and abstract reading. Search terms included "direct" AND "anticoagulant" AND "diverticular bleed" OR "diverticular hemorrhage". The references of the selected studies were manually reviewed for any further relevant articles.
RESULTS
Literature search across the databases garnered 182 articles-157 unique abstracts after duplicate removal. Based on inclusion and exclusion criteria, 6 studies were deemed relevant. The selected studies' reference lists yielded no further relevant articles.
DISCUSSION
Across the 6 studies, the incidence of diverticular bleeding in patients using DOACs was extremely low. Of 23,990 patients taking DOACs identified from two separate institutions, only 60 were found to have diverticular hemorrhage. Similarly, among 15,056 patients with diverticular hemorrhage, only 246 (1.6%) among them were taking DOACs. Generally, the studies found no increased diverticular bleeding rate between patients taking DOACs and those who were taking other anticoagulants, such as warfarin, or the general population. The studies also did not find an increased risk of rebleeding with DOAC continuation.
CONCLUSION
The evidence suggests the risk of diverticular bleed among DOAC users is equivocal to those not taking DOACs, and the overall incidence of diverticular bleed in the DOAC population is low. As it stands, the risk of thrombotic events from not starting DOACs apparently outweighs the risk of diverticular bleed.
Topics: Administration, Oral; Anticoagulants; Diverticulum; Gastrointestinal Hemorrhage; Humans; Risk Factors
PubMed: 31316948
DOI: 10.1155/2019/9851307 -
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 -
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 -
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