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Frontiers in Cardiovascular Medicine 2022Several studies have summarized the clinical performance of direct oral anticoagulants (DOACs) in atrial fibrillation (AF) patients with mitral stenosis or aortic...
BACKGROUND
Several studies have summarized the clinical performance of direct oral anticoagulants (DOACs) in atrial fibrillation (AF) patients with mitral stenosis or aortic stenosis. The significance of this review was to provide clinicians the latest update of the clinical application of DOACs in managing this specific population.
METHODS
Literatures from the PubMed database up to July 2022 were screened for inclusion. Studies on the effect of DOACs in patients suffering from AF with mitral or aortic stenosis were assessed for further selection.
RESULTS
Results from four studies were gathered: the RISE MS trial, the DAVID-MS study, and two observational studies. In the Korean observational study with a 27-month follow-up duration and a sample population consisted of patients with mitral stenosis and AF, the thromboembolic events happened at a rate of 2.22%/ year in the DOAC group and 4.19%/year in the warfarin group (adjusted hazard ratio: 0.28; 95% CI: 0.18-0.45). Intracranial hemorrhage occurred at rates of 0.49% and 0.93% in the DOAC and the warfarin groups, respectively (adjusted hazard ratio: 0.53; 95% CI: 0.22-1.26). In the Danish observational study, which had a sample pool with AF patients with aortic stenosis, reported that the adjusted hazard ratios for thromboembolism and major bleeding were 1.62 (95% CI, 1.08-2.45) and 0.73 (95% CI, 0.59-0.91) for DOACs compared with warfarin during 3 years of follow-up. In the RISE-MS trial involving AF patients with mitral stenosis, there were no differences in ischemic stroke, systemic embolic events, or major bleeding between the rivaroxaban vs. warfarin groups during a 1-year follow-up as well as equal rate of increased thrombogenicity in the left atrial appendage at 6 months. The rate of silent cerebral ischemia at 12 months was higher in the warfarin group (17.6%) than that in the rivaroxaban group (13.3%).
CONCLUSIONS
Current published studies supported DOACs' effectiveness in preventing thromboembolism in patients of AF with mitral or aortic stenosis. Further clinical trials could confirm these findings.
PubMed: 36465442
DOI: 10.3389/fcvm.2022.1070806 -
Cerebrovascular Diseases (Basel,... 2023This meta-analysis assessed the predictors of symptomatic intracranial hemorrhage (sICH) after endovascular thrombectomy (EVT) for patients with acute ischemic stroke. (Meta-Analysis)
Meta-Analysis
INTRODUCTION
This meta-analysis assessed the predictors of symptomatic intracranial hemorrhage (sICH) after endovascular thrombectomy (EVT) for patients with acute ischemic stroke.
METHODS
PubMed, Embase, the Cochrane Central Register of Controlled Trials, and Web of Science were searched for studies published from inception to February 16, 2021. We included studies that evaluated the predictors of sICH after EVT. The random-effect model or fixed-effect model was used to pool the estimates according to the heterogeneity.
RESULTS
A total of 25 cohort studies, involving 15,324 patients, were included in this meta-analysis. The total incidence of sICH was 6.72 percent. Age (MD = 2.57, 95% CI: 1.53-3.61; p < 0.00001), higher initial NIHSS score (MD = 1.71, 95% CI: 1.35-2.08, p < 0.00001), higher initial systolic blood pressure (MD = 7.40, 95% CI: 5.11-9.69, p < 0.00001), diabetes mellitus (OR = 1.36, 95% CI: 1.10-1.69, p = 0.005), poor collaterals (OR = 3.26, 95% CI: 2.35-4.51; p < 0.0001), internal carotid artery occlusion (OR = 1.55, 95% CI: 1.26-1.90; p < 0.0001), longer procedure time (MD = 18.92, 95% CI: 11.49-26.35; p < 0.0001), and passes of retriever >3 (OR = 3.39, 95% CI: 2.45-4.71; p < 0.0001) were predictors of sICH, while modified thrombolysis in cerebral infarction score ≥2b (OR = 0.61, 95% CI: 0.46-0.79; p = 0.0002) was associated with a decreased risk of sICH. There were no significant differences in the female gender, initial serum glucose, initial ASPECT score, atrial fibrillation, oral anticoagulants, antiplatelet therapy, intravenous thrombolysis, general anesthesia, neutrophil-to-lymphocyte ratio, and emergent stenting.
CONCLUSIONS
This study identified many predictors of sICH. Some of the results lack robust evidence given the limitations of the study. Therefore, larger cohort studies are needed to confirm these predictors.
Topics: Humans; Female; Stroke; Ischemic Stroke; Intracranial Hemorrhages; Thrombectomy; Cohort Studies
PubMed: 36423584
DOI: 10.1159/000527193 -
Journal of Psychiatric Research Dec 2022A systematic review was conducted to investigate prevalence, management and outcomes of atrial fibrillation (AF) in people with Serious Mental Illnesses (SMI) versus the... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
A systematic review was conducted to investigate prevalence, management and outcomes of atrial fibrillation (AF) in people with Serious Mental Illnesses (SMI) versus the general population.
DATA SOURCES
MEDLINE, EMBASE, and PsycINFO were searched for primary research written in English and published between 2004 and 2022.
STUDY SELECTION
A total of 1459 studies were identified in the initial search of which 16 met the inclusion criteria. Studies (n = 4) reporting on ischaemic stroke and major bleeding events were included in the meta-analysis.
DATA EXTRACTION
Two independent reviewers extracted data and assessed risk of bias using the Newcastle-Ottawa Scale. Discrepancies were resolved by consulting a third reviewer.
RESULTS
Low rates of AF were reported among people with SMI suggesting under-recognition or recording gaps. People with SMI and AF were less likely to receive oral anticoagulation therapy compared to the general population. When receiving warfarin, those with bipolar disorder experienced poor anticoagulation control as measured by time in INR therapeutic range. Pooled analysis of risk estimates showed that in patients with identified AF, SMI was not significantly associated with an increased risk of stroke (HR: 1.09; 95%CI: 0.85 to 1.40; I = 60%, p = 0.04) or major bleeding (HR: 1.11; 95%CI: 0.95 to 1.28; I = 57%, p = 0.03) when adjusted for underlying stroke and bleeding risks using the CHA2DS2VASc and HASBLED scales respectively.
CONCLUSION
More research is needed to examine the prevalence, management and outcomes of AF in this population, and to evaluate the effect of the introduction of the novel anti-coagulants on these metrics over time.
Topics: Humans; Atrial Fibrillation; Brain Ischemia; Stroke; Hemorrhage; Anticoagulants; Mental Disorders
PubMed: 36417811
DOI: 10.1016/j.jpsychires.2022.11.002 -
The Cochrane Database of Systematic... Nov 2022Venous thromboembolism (VTE), which comprises deep vein thrombosis (DVT) and pulmonary embolism (PE), is the leading cause of preventable death in hospitalised people... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Venous thromboembolism (VTE), which comprises deep vein thrombosis (DVT) and pulmonary embolism (PE), is the leading cause of preventable death in hospitalised people and the third most common cause of mortality in surgical patients. People undergoing bariatric surgery have the additional risk factor of being overweight. Although VTE prophylaxis in surgical patients is well established, the best way to prevent VTE in those undergoing bariatric surgery is less clear.
OBJECTIVES
To evaluate the benefits and harms of pharmacological interventions (alone or in combination) on venous thromboembolism and other health outcomes in people undergoing bariatric surgery compared to the same pharmacological intervention administered at a different dose or frequency, the same pharmacological intervention or started at a different time point, another pharmacological intervention, no intervention or placebo.
SEARCH METHODS
We used standard, extensive Cochrane search methods. The latest search date was 1 November 2021.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) and quasi-RCTs in males and females of any age undergoing bariatric surgery comparing pharmacological interventions for VTE (alone or in combination) with the same pharmacological intervention administered at a different dose or frequency, the same pharmacological intervention started at a different time point, a different pharmacological intervention, no treatment or placebo.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methods. Our primary outcomes were 1. VTE and 2. major bleeding. Our secondary outcomes were 1. all-cause mortality, 2. VTE-related mortality, 3. PE, 4. DVT, 5. adverse effects and 6. quality of life. We used GRADE to assess certainty of evidence for each outcome.
MAIN RESULTS
We included seven RCTs with 1045 participants. Data for meta-analysis were available from all participants. Four RCTs (597 participants) compared higher-dose heparin to standard-dose heparin: one of these studies (139 participants) used unfractionated heparin (UFH) and the other three (458 participants) used low-molecular-weight heparin (LMWH). One study compared heparin versus pentasaccharide (198 participants), and one study compared starting heparin before versus after bariatric surgery (100 participants). One study (150 participants) compared combined mechanical and pharmacological (enoxaparin) prophylaxis versus mechanical prophylaxis alone. The duration of the interventions ranged from seven to 15 days, and follow-up ranged from 10 to 180 days. Higher-dose heparin versus standard-dose heparin Compared to standard-dose heparin, higher-dose heparin may result in little or no difference in the risk of VTE (RR 0.55, 95% CI 0.05 to 5.99; 4 studies, 597 participants) or major bleeding (RR 1.19, 95% CI 0.48 to 2.96; I = 8%; 4 studies, 597 participants; low-certainty) in people undergoing bariatric surgery. The evidence on all-cause mortality, VTE-related mortality, PE, DVT and adverse events (thrombocytopenia) is uncertain (effect not estimable or very low-certainty evidence). Heparin versus pentasaccharide Heparin compared to a pentasaccharide after bariatric surgery may result in little or no difference in the risk of VTE (RR 0.83, 95% CI 0.19 to 3.61; 1 study, 175 participants) or DVT (RR 0.83, 95% CI 0.19 to 3.61; 1 study, 175 participants). The evidence on major bleeding, PE and mortality is uncertain (effect not estimable or very low-certainty evidence). Heparin started before versus after the surgical procedure Starting prophylaxis with heparin 12 hours before surgery versus after surgery may result in little or no difference in the risk of VTE (RR 0.11, 95% CI 0.01 to 2.01; 1 study, 100 participants) or DVT (RR 0.11, 95% CI 0.01 to 2.01; 1 study, 100 participants). The evidence on major bleeding, all-cause mortality and VTE-related mortality is uncertain (effect not estimable or very low-certainty evidence). We were unable to assess the effect of this intervention on PE or adverse effects, as the study did not measure these outcomes. Combined mechanical and pharmacological prophylaxis versus mechanical prophylaxis alone Combining mechanical and pharmacological prophylaxis (started 12 hours before surgery) may reduce VTE events in people undergoing bariatric surgery compared to mechanical prophylaxis alone (RR 0.05, 95% CI 0.00 to 0.89; number needed to treat for an additional beneficial outcome (NNTB) = 9; 1 study, 150 participants; low-certainty). We were unable to assess the effect of this intervention on major bleeding or morality (effect not estimable), or on PE or adverse events (not measured). No studies measured quality of life.
AUTHORS' CONCLUSIONS
Higher-dose heparin may make little or no difference to venous thromboembolism or major bleeding in people undergoing bariatric surgery when compared to standard-dose heparin. Heparin may make little or no difference to venous thromboembolism in people undergoing bariatric surgery when compared to pentasaccharide. There are inadequate data to draw conclusions about the effects of heparin compared to pentasaccharide on major bleeding. Starting prophylaxis with heparin 12 hours before bariatric surgery may make little or no difference to venous thromboembolism in people undergoing bariatric surgery when compared to starting heparin after bariatric surgery. There are inadequate data to draw conclusions about the effects of heparin started before versus after surgery on major bleeding. Combining mechanical and pharmacological prophylaxis (started 12 hours before surgery) may reduce VTE events in people undergoing bariatric surgery when compared to mechanical prophylaxis alone. No data are available relating to major bleeding. The certainty of the evidence is limited by small sample sizes, few or no events, and risk of bias concerns. Future trials must be sufficiently large to enable analysis of relevant clinical outcomes, and should standardise the time of treatment and follow-up. They should also address the effect of direct oral anticoagulants and antiplatelets, preferably grouping them according to the type of intervention.
Topics: Female; Humans; Male; Anticoagulants; Bariatric Surgery; Hemorrhage; Heparin; Pulmonary Embolism; Venous Thromboembolism; Randomized Controlled Trials as Topic
PubMed: 36413425
DOI: 10.1002/14651858.CD013683.pub2 -
The Cochrane Database of Systematic... Nov 2022Rebleeding is an important cause of death and disability in people with aneurysmal subarachnoid haemorrhage. Rebleeding is probably related to the dissolution of the... (Review)
Review
BACKGROUND
Rebleeding is an important cause of death and disability in people with aneurysmal subarachnoid haemorrhage. Rebleeding is probably related to the dissolution of the blood clot at the site of the aneurysm rupture by natural fibrinolytic activity. This review is an update of previously published Cochrane Reviews.
OBJECTIVES
To assess the effects of antifibrinolytic treatment in people with aneurysmal subarachnoid haemorrhage.
SEARCH METHODS
We searched the Cochrane Stroke Group Trials Register (May 2022), CENTRAL (in the Cochrane Library 2021, Issue 1), MEDLINE (December 2012 to May 2022), and Embase (December 2012 to May 2022). In an effort to identify further published, unpublished, and ongoing studies, we searched reference lists and trial registers, performed forward tracking of relevant references, and contacted drug companies (the latter in previous versions of this review).
SELECTION CRITERIA
Randomised trials comparing oral or intravenous antifibrinolytic drugs (tranexamic acid, epsilon amino-caproic acid, or an equivalent) with control in people with subarachnoid haemorrhage of suspected or proven aneurysmal cause.
DATA COLLECTION AND ANALYSIS
Two review authors (MRG & WJD) independently selected trials for inclusion, and extracted the data for the current update. In total, three review authors (MIB & MRG in the previous update; MRG & WJD in the current update) assessed risk of bias. For the primary outcome, we dichotomised the outcome scales into good and poor outcome, with poor outcome defined as death, vegetative state, or (moderate) severe disability, assessed with either the Glasgow Outcome Scale or the Modified Rankin Scale. We assessed death from any cause, rates of rebleeding, delayed cerebral ischaemia, and hydrocephalus per treatment group. We expressed effects as risk ratios (RR) with 95% confidence intervals (CI). We used random-effects models for all analyses. We assessed the quality of the evidence with GRADE.
MAIN RESULTS
We included one new trial in this update, for a total of 11 included trials involving 2717 participants. The risk of bias was low in six studies. Five studies were open label, and we rated them at high risk of performance bias. We also rated one of these studies at high risk for attrition and reporting bias. Five trials reported on poor outcome (death, vegetative state, or (moderate) severe disability), with a pooled risk ratio (RR) of 1.03 (95% confidence interval (CI) 0.94 to 1.13; P = 0.53; 5 trials, 2359 participants; high-quality evidence), which showed no difference between groups. All trials reported on death from all causes, which showed no difference between groups, with a pooled RR of 1.02 (95% CI 0.90 to 1.16; P = 0.77; 11 trials, 2717 participants; high-quality evidence). In trials that combined short-term antifibrinolytic treatment (< 72 hours) with preventative measures for delayed cerebral ischaemia, the RR for poor outcome was 0.98 (95% CI 0.81 to 1.18; P = 0.83; 2 trials, 1318 participants; high-quality evidence). Antifibrinolytic treatment reduced the risk of rebleeding, reported at the end of follow-up (RR 0.65, 95% CI 0.47 to 0.91; P = 0.01; 11 trials, 2717 participants; absolute risk reduction 7%, 95% CI 3 to 12%; moderate-quality evidence), but there was heterogeneity (I² = 59%) between the trials. The pooled RR for delayed cerebral ischaemia was 1.27 (95% CI 1.00 to 1.62; P = 0.05; 7 trials, 2484 participants; moderate-quality evidence). However, this effect was less extreme after the implementation of ischaemia preventative measures and < 72 hours of treatment (RR 1.10, 95% CI 0.83 to 1.46; P = 0.49; 2 trials, 1318 participants; high-quality evidence). Antifibrinolytic treatment showed no effect on the reported rate of hydrocephalus (RR 1.09, 95% CI 0.99 to 1.20; P = 0.09; 6 trials, 1992 participants; high-quality evidence).
AUTHORS' CONCLUSIONS
The current evidence does not support the routine use of antifibrinolytic drugs in the treatment of people with aneurysmal subarachnoid haemorrhage. More specifically, early administration with concomitant treatment strategies to prevent delayed cerebral ischaemia does not improve clinical outcome. There is sufficient evidence from multiple randomised controlled trials to incorporate this conclusion in treatment guidelines.
Topics: Humans; Subarachnoid Hemorrhage; Antifibrinolytic Agents; Persistent Vegetative State; Brain Ischemia; Hydrocephalus
PubMed: 36350005
DOI: 10.1002/14651858.CD001245.pub3 -
JAMA Network Open Nov 2022Direct oral anticoagulant (DOAC)-associated intracranial hemorrhage (ICH) has high morbidity and mortality. The safety and outcome data of DOAC reversal agents in ICH... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Direct oral anticoagulant (DOAC)-associated intracranial hemorrhage (ICH) has high morbidity and mortality. The safety and outcome data of DOAC reversal agents in ICH are limited.
OBJECTIVE
To evaluate the safety and outcomes of DOAC reversal agents among patients with ICH.
DATA SOURCES
PubMed, MEDLINE, The Cochrane Library, Embase, EBSCO, Web of Science, and CINAHL databases were searched from inception through April 29, 2022.
STUDY SELECTION
The eligibility criteria were (1) adult patients (age ≥18 years) with ICH receiving treatment with a DOAC, (2) reversal of DOAC, and (3) reported safety and anticoagulation reversal outcomes. All nonhuman studies and case reports, studies evaluating patients with ischemic stroke requiring anticoagulation reversal or different dosing regimens of DOAC reversal agents, and mixed study groups with DOAC and warfarin were excluded.
DATA EXTRACTION AND SYNTHESIS
Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines were used for abstracting data and assessing data quality and validity. Two reviewers independently selected the studies and abstracted data. Data were pooled using the random-effects model.
MAIN OUTCOMES AND MEASURES
The primary outcome was proportion with anticoagulation reversed. The primary safety end points were all-cause mortality and thromboembolic events after the reversal agent.
RESULTS
A total of 36 studies met criteria for inclusion, with a total of 1832 patients (967 receiving 4-factor prothrombin complex concentrate [4F-PCC]; 525, andexanet alfa [AA]; 340, idarucizumab). The mean age was 76 (range, 68-83) years, and 57% were men. For 4F-PCC, anticoagulation reversal was 77% (95% CI, 72%-82%; I2 = 55%); all-cause mortality, 26% (95% CI, 20%-32%; I2 = 68%), and thromboembolic events, 8% (95% CI, 5%-12%; I2 = 41%). For AA, anticoagulation reversal was 75% (95% CI, 67%-81%; I2 = 48%); all-cause mortality, 24% (95% CI, 16%-34%; I2 = 73%), and thromboembolic events, 14% (95% CI, 10%-19%; I2 = 16%). Idarucizumab for reversal of dabigatran had an anticoagulation reversal rate of 82% (95% CI, 55%-95%; I2 = 41%), all-cause mortality, 11% (95% CI, 8%-15%, I2 = 0%), and thromboembolic events, 5% (95% CI, 3%-8%; I2 = 0%). A direct retrospective comparison of 4F-PCC and AA showed no differences in anticoagulation reversal, proportional mortality, or thromboembolic events.
CONCLUSIONS AND RELEVANCE
In the absence of randomized clinical comparison trials, the overall anticoagulation reversal, mortality, and thromboembolic event rates in this systematic review and meta-analysis appeared similar among available DOAC reversal agents for managing ICH. Cost, institutional formulary status, and availability may restrict reversal agent choice, particularly in small community hospitals.
Topics: Male; Adult; Humans; Aged; Adolescent; Female; Hemorrhage; Retrospective Studies; Anticoagulant Reversal Agents; Anticoagulation Reversal; Anticoagulants; Intracranial Hemorrhages; Thromboembolism
PubMed: 36331504
DOI: 10.1001/jamanetworkopen.2022.40145 -
Journal of the American College of... Jan 2023The efficacy and safety of direct oral anticoagulants (DOACs) for patients with thrombotic antiphospholipid syndrome remain controversial. (Meta-Analysis)
Meta-Analysis
BACKGROUND
The efficacy and safety of direct oral anticoagulants (DOACs) for patients with thrombotic antiphospholipid syndrome remain controversial.
OBJECTIVES
The authors performed a systematic review and meta-analysis of randomized controlled trials that compared DOACs with vitamin K antagonists (VKAs).
METHODS
We searched PubMed, EMBASE, and Cochrane Central Register of Controlled Trials through April 9, 2022. The 2 main efficacy outcomes were a composite of arterial thrombotic events and venous thromboembolic events (VTEs). The main safety outcome was major bleeding. Random effects models with inverse variance were used.
RESULTS
Our search retrieved 253 studies. Four open-label randomized controlled trials involving 472 patients were included (mean control-arm time-in-therapeutic-range 60%). All had proper random sequence generation and adequate allocation concealment. Overall, the use of DOACs compared with VKAs was associated with increased odds of subsequent arterial thrombotic events (OR: 5.43; 95% CI: 1.87-15.75; P < 0.001, I = 0%), especially stroke, and the composite of arterial thrombotic events or VTE (OR: 4.46; 95% CI: 1.12-17.84; P = 0.03, I = 0%). The odds of subsequent VTE (OR: 1.20; 95% CI: 0.31-4.55; P = 0.79, I = 0%), or major bleeding (OR: 1.02; 95% CI: 0.42-2.47; P = 0.97; I = 0%) were not significantly different between the 2 groups. Most findings were consistent within subgroups.
CONCLUSIONS
Patients with thrombotic antiphospholipid syndrome randomized to DOACs compared with VKAs appear to have increased risk for arterial thrombosis. No significant differences were observed between patients randomized to DOACs vs VKAs in the risk of subsequent VTE or major bleeding.
Topics: Humans; Administration, Oral; Anticoagulants; Antiphospholipid Syndrome; Fibrinolytic Agents; Hemorrhage; Randomized Controlled Trials as Topic; Thrombosis; Venous Thromboembolism; Vitamin K
PubMed: 36328154
DOI: 10.1016/j.jacc.2022.10.008 -
European Journal of Clinical... Dec 2022This systematic review and meta-analysis aimed to determine whether tramadol intake increases the risk of bleeding in patients receiving oral anticoagulants. (Meta-Analysis)
Meta-Analysis Review
PURPOSE
This systematic review and meta-analysis aimed to determine whether tramadol intake increases the risk of bleeding in patients receiving oral anticoagulants.
METHODS
This systematic review was registered on PROSPERO, CRD42022327230. We searched PubMed and Embase up to 14 April 2022, and references and citations of included studies were screened. Comparative and non-comparative studies exploring bleeding complications among adult patients on oral anticoagulants and tramadol were included. Risk of bias was assessed using an adaptation of the Drug Interaction Probability Scale for case reports and case series and the Newcastle-Ottawa Scale for comparative studies. A meta-analysis was performed for the risk of serious bleeding (leading to hospitalisation or death) associated with tramadol in patients on vitamin K antagonists.
RESULTS
A total of 17 studies were included: 1 case series, 12 case reports, 2 case-control studies and 2 cohort studies. Most of the studies described tramadol-vitamin K antagonists' concomitant use; one case-control study also assessed dabigatran and rivaroxaban; one case report involved dabigatran. Among case reports/series, a total of 33 patients had a bleeding complication while using tramadol and an oral anticoagulant. The 4 comparative studies reported an increased bleeding risk during tramadol and vitamin K antagonist intake which was statistically significant in one study; the pooled risk ratio of serious bleeding was 2.68 [95% CI: 1.45 to 4.96; p < 0.001].
CONCLUSION
This systematic review confirms an association between tramadol use and risk of bleeding in patients on vitamin K antagonists. Evidence is too limited to assess whether this risk extends to patients on direct oral anticoagulants, and further studies are needed.
Topics: Adult; Humans; Dabigatran; Tramadol; Case-Control Studies; Administration, Oral; Anticoagulants; Rivaroxaban; Hemorrhage; Fibrinolytic Agents; Vitamin K; Atrial Fibrillation
PubMed: 36323905
DOI: 10.1007/s00228-022-03411-1 -
Heart (British Cardiac Society) Jan 2023There has been limited systematic evaluation of outcomes and drivers of inappropriate non-vitamin K antagonist oral anticoagulants (NOACs) dosing among patients with... (Meta-Analysis)
Meta-Analysis
Outcomes and drivers of inappropriate dosing of non-vitamin K antagonist oral anticoagulants (NOACs) in patients with atrial fibrillation: a systematic review and meta-analysis.
OBJECTIVE
There has been limited systematic evaluation of outcomes and drivers of inappropriate non-vitamin K antagonist oral anticoagulants (NOACs) dosing among patients with atrial fibrillation (AF). This review identified and systematically evaluated literature on clinical and economic outcomes of inappropriate NOAC dosing and associated patient characteristics.
METHODS
MEDLINE, Embase, Cochrane Library, International Pharmaceutical Abstracts, Econlit, PubMed and NHS EEDs databases were searched for English language observational studies from all geographies published between 2008 and 2020, examining outcomes of, or factors associated with, inappropriate NOAC dosing in adult patients with AF.
RESULTS
One hundred and six studies were included in the analysis. Meta-analysis showed that compared with recommended NOAC dosing, off-label underdosing was associated with a null effect on stroke outcomes (ischaemic stroke and stroke/transient ischaemic attack (TIA), stroke/systemic embolism (SE) and stroke/SE/TIA). Meta-analysis of 15 studies examining clinical outcomes of inappropriate NOAC dosing found a null effect of underdosing on bleeding outcomes (major bleeding HR=1.04, 95% CI 0.90 to 1.19; p=0.625) but an increased risk of all-cause mortality (HR=1.28, 95% CI 1.10 to 1.49; p=0.006). Overdosing was associated with an increased risk of major bleeding (HR=1.41, 95% CI 1.07 to 1.85; p=0.013). No studies were found examining economic outcomes of inappropriate NOAC dosing. Narrative synthesis of 12 studies examining drivers of inappropriate NOAC dosing found that increased age, history of minor bleeds, hypertension, congestive heart failure and low creatine clearance (CrCl) were associated with an increased risk of underdosing. There was insufficient evidence to assess drivers of overdosing.
CONCLUSIONS
Our analysis suggests that off-label underdosing of NOACs does not reduce bleeding outcomes. Patients prescribed off-label NOAC doses are at an increased risk of all-cause mortality. These data underscore the importance of prescriber adherence to NOAC dosing guidelines to achieve optimal clinical outcomes for patients with AF.
PROSPERO REGISTRATION NUMBER
CRD42020219844.
Topics: Adult; Humans; Anticoagulants; Atrial Fibrillation; Stroke; Administration, Oral; Brain Ischemia; Ischemic Attack, Transient; Hemorrhage; Embolism
PubMed: 36316100
DOI: 10.1136/heartjnl-2022-321114 -
Frontiers in Neurology 2022In clinical practice, nimodipine is used to control cerebral vasospasm (CVS), which is one of the major causes of severe disability and mortality in patients with...
OBJECTIVE
In clinical practice, nimodipine is used to control cerebral vasospasm (CVS), which is one of the major causes of severe disability and mortality in patients with aneurysmal subarachnoid hemorrhage (aSAH). However, the exact efficacy of nimodipine use for patients with aSAH is still controversial due to the lack of sufficient and up-to-date evidence.
METHODS
In this meta-analysis, the latest databases of the Cochrane Central Register of Controlled Trials, PubMed-Medline, Web of Science, Embase, Scopus, and OVID-Medline were comprehensively searched for retrieving all randomized controlled trials (RCTs) regarding the efficacy of nimodipine in patients with aSAH. The primary outcome was a poor outcome, and the secondary outcomes were mortality and cerebral vasospasm (CVS). After detailed statistical analysis of different outcome variables, further evidence quality evaluation and recommendation grade assessment were carried out.
RESULTS
Approximately 13 RCTs met the inclusion criteria, and a total of 1,727 patients were included. Meta-analysis showed that a poor outcome was significantly reduced in the nimodipine group [RR, 0.69 (0.60-0.78); I = 29%]. Moreover, nimodipine also dramatically decreased the mortality [RR, 0.50 (0.32-0.78); I = 62%] and the incidence of CVS [RR, 0.68 (0.46-0.99); I = 57%]. Remarkably, we found a poor outcome and mortality were both significantly lower among patients with aSAH, with the mean age < 50 than that mean age ≥ 50 by subgroup analysis. Furthermore, the evidence grading of a poor outcome and its age subgroup in this study was assessed as high.
CONCLUSION
Nimodipine can significantly reduce the incidence of a poor outcome, mortality, and CVS in patients with aSAH. Moreover, we strongly recommend that patients with aSAH, especially those younger than 50 years old, should use nimodipine as early as possible in order to achieve a better clinical outcome, whether oral medication or endovascular direct medication.
SYSTEMATIC REVIEW REGISTRATION
www.york.ac.uk/inst/crd, identifier: CRD42022334619.
PubMed: 36212656
DOI: 10.3389/fneur.2022.982498