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Journal of Gastroenterology Apr 2021The Japanese Society of Gastroenterology (JSGE) revised the third edition of evidence-based clinical practice guidelines for peptic ulcer disease in 2020 and created an...
The Japanese Society of Gastroenterology (JSGE) revised the third edition of evidence-based clinical practice guidelines for peptic ulcer disease in 2020 and created an English version. The revised guidelines consist of nine items: epidemiology, hemorrhagic gastric and duodenal ulcers, Helicobacter pylori (H. pylori) eradication therapy, non-eradication therapy, drug-induced ulcers, non-H. pylori, and nonsteroidal anti-inflammatory drug (NSAID) ulcers, remnant gastric ulcers, surgical treatment, and conservative therapy for perforation and stenosis. Therapeutic algorithms for the treatment of peptic ulcers differ based on ulcer complications. In patients with NSAID-induced ulcers, NSAIDs are discontinued and anti-ulcer therapy is administered. If NSAIDs cannot be discontinued, the ulcer is treated with proton pump inhibitors (PPIs). Vonoprazan (VPZ) with antibiotics is recommended as the first-line treatment for H. pylori eradication, and PPIs or VPZ with antibiotics is recommended as a second-line therapy. Patients who do not use NSAIDs and are H. pylori negative are considered to have idiopathic peptic ulcers. Algorithms for the prevention of NSAID- and low-dose aspirin (LDA)-related ulcers are presented in this guideline. These algorithms differ based on the concomitant use of LDA or NSAIDs and ulcer history or hemorrhagic ulcer history. In patients with a history of ulcers receiving NSAID therapy, PPIs with or without celecoxib are recommended and the administration of VPZ is suggested for the prevention of ulcer recurrence. In patients with a history of ulcers receiving LDA therapy, PPIs or VPZ are recommended and the administration of a histamine 2-receptor antagonist is suggested for the prevention of ulcer recurrence.
Topics: Humans; Anti-Bacterial Agents; Evidence-Based Practice; Japan; Peptic Ulcer; Proton Pump Inhibitors
PubMed: 33620586
DOI: 10.1007/s00535-021-01769-0 -
Annals of the Rheumatic Diseases Mar 2017Develop recommendations for women's health issues and family planning in systemic lupus erythematosus (SLE) and/or antiphospholipid syndrome (APS).
EULAR recommendations for women's health and the management of family planning, assisted reproduction, pregnancy and menopause in patients with systemic lupus erythematosus and/or antiphospholipid syndrome.
OBJECTIVES
Develop recommendations for women's health issues and family planning in systemic lupus erythematosus (SLE) and/or antiphospholipid syndrome (APS).
METHODS
Systematic review of evidence followed by modified Delphi method to compile questions, elicit expert opinions and reach consensus.
RESULTS
Family planning should be discussed as early as possible after diagnosis. Most women can have successful pregnancies and measures can be taken to reduce the risks of adverse maternal or fetal outcomes. Risk stratification includes disease activity, autoantibody profile, previous vascular and pregnancy morbidity, hypertension and the use of drugs (emphasis on benefits from hydroxychloroquine and antiplatelets/anticoagulants). Hormonal contraception and menopause replacement therapy can be used in patients with stable/inactive disease and low risk of thrombosis. Fertility preservation with gonadotropin-releasing hormone analogues should be considered prior to the use of alkylating agents. Assisted reproduction techniques can be safely used in patients with stable/inactive disease; patients with positive antiphospholipid antibodies/APS should receive anticoagulation and/or low-dose aspirin. Assessment of disease activity, renal function and serological markers is important for diagnosing disease flares and monitoring for obstetrical adverse outcomes. Fetal monitoring includes Doppler ultrasonography and fetal biometry, particularly in the third trimester, to screen for placental insufficiency and small for gestational age fetuses. Screening for gynaecological malignancies is similar to the general population, with increased vigilance for cervical premalignant lesions if exposed to immunosuppressive drugs. Human papillomavirus immunisation can be used in women with stable/inactive disease.
CONCLUSIONS
Recommendations for women's health issues in SLE and/or APS were developed using an evidence-based approach followed by expert consensus.
Topics: Antiphospholipid Syndrome; Contraceptives, Oral, Hormonal; Delphi Technique; Early Detection of Cancer; Estrogen Replacement Therapy; Family Planning Services; Female; Fertility Preservation; Fetal Monitoring; Genital Neoplasms, Female; Humans; Lupus Erythematosus, Systemic; Menopause; Preconception Care; Pregnancy; Pregnancy Complications; Reproductive Techniques, Assisted; Risk Assessment
PubMed: 27457513
DOI: 10.1136/annrheumdis-2016-209770 -
JAMA Jan 2019The role for aspirin in cardiovascular primary prevention remains controversial, with potential benefits limited by an increased bleeding risk. (Meta-Analysis)
Meta-Analysis
IMPORTANCE
The role for aspirin in cardiovascular primary prevention remains controversial, with potential benefits limited by an increased bleeding risk.
OBJECTIVE
To assess the association of aspirin use for primary prevention with cardiovascular events and bleeding.
DATA SOURCES
PubMed and Embase were searched on Cochrane Library Central Register of Controlled Trials from the earliest available date through November 1, 2018.
STUDY SELECTION
Randomized clinical trials enrolling at least 1000 participants with no known cardiovascular disease and a follow-up of at least 12 months were included. Included studies compared aspirin use with no aspirin (placebo or no treatment).
DATA EXTRACTION AND SYNTHESIS
Data were screened and extracted independently by both investigators. Bayesian and frequentist meta-analyses were performed.
MAIN OUTCOMES AND MEASURES
The primary cardiovascular outcome was a composite of cardiovascular mortality, nonfatal myocardial infarction, and nonfatal stroke. The primary bleeding outcome was any major bleeding (defined by the individual studies).
RESULTS
A total of 13 trials randomizing 164 225 participants with 1 050 511 participant-years of follow-up were included. The median age of trial participants was 62 years (range, 53-74), 77 501 (47%) were men, 30 361 (19%) had diabetes, and the median baseline risk of the primary cardiovascular outcome was 9.2% (range, 2.6%-15.9%). Aspirin use was associated with significant reductions in the composite cardiovascular outcome compared with no aspirin (57.1 per 10 000 participant-years with aspirin and 61.4 per 10 000 participant-years with no aspirin) (hazard ratio [HR], 0.89 [95% credible interval, 0.84-0.95]; absolute risk reduction, 0.38% [95% CI, 0.20%-0.55%]; number needed to treat, 265). Aspirin use was associated with an increased risk of major bleeding events compared with no aspirin (23.1 per 10 000 participant-years with aspirin and 16.4 per 10 000 participant-years with no aspirin) (HR, 1.43 [95% credible interval, 1.30-1.56]; absolute risk increase, 0.47% [95% CI, 0.34%-0.62%]; number needed to harm, 210).
CONCLUSIONS AND RELEVANCE
The use of aspirin in individuals without cardiovascular disease was associated with a lower risk of cardiovascular events and an increased risk of major bleeding. This information may inform discussions with patients about aspirin for primary prevention of cardiovascular events and bleeding.
Topics: Aspirin; Cardiovascular Diseases; Diabetes Complications; Diabetes Mellitus; Female; Hemorrhage; Humans; Male; Platelet Aggregation Inhibitors; Primary Prevention; Risk
PubMed: 30667501
DOI: 10.1001/jama.2018.20578 -
BMJ (Clinical Research Ed.) Apr 2016To develop a practical evidence based list of clinical risk factors that can be assessed by a clinician at ≤ 16 weeks' gestation to estimate a woman's risk of... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To develop a practical evidence based list of clinical risk factors that can be assessed by a clinician at ≤ 16 weeks' gestation to estimate a woman's risk of pre-eclampsia.
DESIGN
Systematic review and meta-analysis of cohort studies.
DATA SOURCES
PubMed and Embase databases, 2000-15.
ELIGIBILITY CRITERIA FOR SELECTING STUDIES
Cohort studies with ≥ 1000 participants that evaluated the risk of pre-eclampsia in relation to a common and generally accepted clinical risk factor assessed at ≤ 16 weeks' gestation.
DATA EXTRACTION
Two independent reviewers extracted data from included studies. A pooled event rate and pooled relative risk for pre-eclampsia were calculated for each of 14 risk factors.
RESULTS
There were 25,356,688 pregnancies among 92 studies. The pooled relative risk for each risk factor significantly exceeded 1.0, except for prior intrauterine growth restriction. Women with antiphospholipid antibody syndrome had the highest pooled rate of pre-eclampsia (17.3%, 95% confidence interval 6.8% to 31.4%). Those with prior pre-eclampsia had the greatest pooled relative risk (8.4, 7.1 to 9.9). Chronic hypertension ranked second, both in terms of its pooled rate (16.0%, 12.6% to 19.7%) and pooled relative risk (5.1, 4.0 to 6.5) of pre-eclampsia. Pregestational diabetes (pooled rate 11.0%, 8.4% to 13.8%; pooled relative risk 3.7, 3.1 to 4.3), prepregnancy body mass index (BMI) >30 (7.1%, 6.1% to 8.2%; 2.8, 2.6 to 3.1), and use of assisted reproductive technology (6.2%, 4.7% to 7.9%; 1.8, 1.6 to 2.1) were other prominent risk factors.
CONCLUSIONS
There are several practical clinical risk factors that, either alone or in combination, might identify women in early pregnancy who are at "high risk" of pre-eclampsia. These data can inform the generation of a clinical prediction model for pre-eclampsia and the use of aspirin prophylaxis in pregnancy.
Topics: Aspirin; Body Mass Index; Chronic Disease; Cohort Studies; Early Diagnosis; Female; Humans; Hypertension, Pregnancy-Induced; Platelet Aggregation Inhibitors; Pre-Eclampsia; Pregnancy; Pregnancy Trimester, First; Pregnancy Trimester, Second; Pregnancy in Diabetics; Prenatal Diagnosis; Randomized Controlled Trials as Topic; Reproductive Techniques, Assisted; Risk Factors
PubMed: 27094586
DOI: 10.1136/bmj.i1753 -
JAMA Internal Medicine Mar 2020Patients undergoing total hip replacement (THR) and total knee replacement (TKR) receive venous thromboembolism (VTE) pharmacoprophylaxis. It is unclear which... (Meta-Analysis)
Meta-Analysis
Clinical Effectiveness and Safety of Aspirin for Venous Thromboembolism Prophylaxis After Total Hip and Knee Replacement: A Systematic Review and Meta-analysis of Randomized Clinical Trials.
IMPORTANCE
Patients undergoing total hip replacement (THR) and total knee replacement (TKR) receive venous thromboembolism (VTE) pharmacoprophylaxis. It is unclear which anticoagulant is preferable. Observational data suggest aspirin provides effective VTE prophylaxis.
OBJECTIVE
To assess the effectiveness and safety of aspirin for VTE prophylaxis after THR and TKR.
DATA SOURCES
A systematic review and meta-analysis was performed of randomized clinical trials (RCTs), with no language restrictions, from inception to September 19, 2019, using MEDLINE, Embase, Web of Science, Cochrane Library, and bibliographic searches. The computer-based searches combined terms and combinations of keywords related to the population (eg, hip replacement, knee replacement, hip arthroplasty, and knee arthroplasty), drug intervention (eg, aspirin, heparin, clexane, dabigatran, rivaroxaban, and warfarin), and outcome (eg, venous thromboembolism, deep vein thrombosis, pulmonary embolism, and bleeding) in humans.
STUDY SELECTION
This study included RCTs assessing the effectiveness and safety of aspirin for VTE prophylaxis compared with other anticoagulants in adults undergoing THR and TKR. The RCTs with a placebo control group were excluded. The searches and study selection were independently performed.
DATA EXTRACTION AND SYNTHESIS
This study followed PRISMA recommendations and used the Cochrane Collaboration's risk of bias tool. Data were screened and extracted independently by both reviewers. Study-specific relative risks (RRs) were aggregated using random-effects models. Quality of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach.
MAIN OUTCOMES AND MEASURES
The primary outcome was any postoperative VTE (asymptomatic or symptomatic). Secondary outcomes were adverse events associated with therapy, including bleeding.
RESULTS
Of 437 identified articles, 13 RCTs were included (6060 participants; 3466 [57.2%] women; mean age, 63.0 years). The RR of VTE after THR and TKR was 1.12 (95% CI, 0.78-1.62) for aspirin compared with other anticoagulants. Comparable findings were observed for deep vein thrombosis (DVT) (RR, 1.04; 95% CI, 0.72-1.51) and pulmonary embolism (PE) (RR, 1.01; 95% CI, 0.68-1.48). The risk of adverse events, including major bleeding, wound hematoma, and wound infection, was not statistically significantly different in patients receiving aspirin vs other anticoagulants. When analyzing THRs and TKRs separately, there was no statistically significant difference in the risk of VTE, DVT, and PE between aspirin and other anticoagulants. Aspirin had a VTE risk not statistically significantly different from low-molecular-weight heparin (RR, 0.76; 95% CI, 0.37-1.56) or rivaroxaban (RR, 1.52; 95% CI, 0.56-4.12). The quality of the evidence ranged from low to high.
CONCLUSIONS AND RELEVANCE
In terms of clinical effectiveness and safety profile, aspirin did not differ statistically significantly from other anticoagulants used for VTE prophylaxis after THR and TKR. Future trials should focus on noninferiority analysis of aspirin compared with alternative anticoagulants and cost-effectiveness.
Topics: Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Aspirin; Fibrinolytic Agents; Humans; Postoperative Complications; Treatment Outcome; Venous Thromboembolism
PubMed: 32011647
DOI: 10.1001/jamainternmed.2019.6108 -
JAMA Neurology Feb 2022Dual antiplatelet therapy (DAPT) with clopidogrel and aspirin is effective in preventing recurrent strokes after minor ischemic stroke or transient ischemic attack... (Comparative Study)
Comparative Study Meta-Analysis
IMPORTANCE
Dual antiplatelet therapy (DAPT) with clopidogrel and aspirin is effective in preventing recurrent strokes after minor ischemic stroke or transient ischemic attack (TIA). However, there is emerging evidence for the use of ticagrelor and aspirin, and the 2 DAPT regimens have not been compared directly.
OBJECTIVE
To compare ticagrelor and aspirin with clopidogrel and aspirin in patients with acute minor ischemic stroke or TIA in the prevention of recurrent strokes or death.
DATA SOURCES
MEDLINE, Embase, and Cochrane from database inception until February 2021.
STUDY SELECTION
Randomized clinical trials that enrolled adults with acute minor ischemic stroke or TIA and provided the mentioned interventions within 72 hours of symptom onset, with a minimum follow-up of 30 days.
DATA EXTRACTION AND SYNTHESIS
PRISMA guidelines for network meta-analyses were followed. Two reviewers independently extracted data and appraised risk of bias. Fixed-effects models were fit using a bayesian approach to network meta-analysis. Between-group comparisons were estimated using hazard ratios (HRs) with 95% credible intervals (95% CrIs). Surface under the cumulative rank curve plots were produced.
MAIN OUTCOMES AND MEASURES
The primary outcome was a composite of recurrent stroke or death up to 90 days. Secondary outcomes include major bleeding, mortality, adverse events, and functional disability. A sensitivity analysis was performed at 30 days for the primary outcome.
RESULTS
A total of 4014 citations were screened; 5 randomized clinical trials were included. Data from 22 098 patients were analyzed, including 5517 in the clopidogrel and aspirin arm, 5859 in the ticagrelor and aspirin arm, and 10 722 in the aspirin arm. Both clopidogrel and aspirin (HR, 0.74; 95% CrI, 0.65-0.84) and ticagrelor and aspirin (HR, 0.79; 95% CrI, 0.68-0.91) were superior to aspirin in the prevention of recurrent stroke and death. There was no statistically significant difference between clopidogrel and aspirin compared with ticagrelor and aspirin (HR, 0.94; 95% CrI, 0.78-1.13). Both DAPT regimens had higher rates of major hemorrhage than aspirin alone. Clopidogrel and aspirin was associated with a decreased risk of functional disability compared with aspirin alone (HR, 0.82; 95% CrI, 0.74-0.91) and ticagrelor and aspirin (HR, 0.85; 95% CrI, 0.75-0.97).
CONCLUSIONS AND RELEVANCE
DAPT combining aspirin with either ticagrelor or clopidogrel was superior to aspirin alone, but there was no statistically significant difference found between the 2 regimens for the primary outcome.
Topics: Aspirin; Clopidogrel; Drug Therapy, Combination; Dual Anti-Platelet Therapy; Humans; Ischemic Attack, Transient; Ischemic Stroke; Network Meta-Analysis; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Recurrence; Ticagrelor
PubMed: 34870698
DOI: 10.1001/jamaneurol.2021.4514 -
Advances in Therapy Jan 2020International guidelines support the use of low molecular weight heparins for the treatment of thromboembolism and thromboprophylaxis during pregnancy. However, evidence... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
International guidelines support the use of low molecular weight heparins for the treatment of thromboembolism and thromboprophylaxis during pregnancy. However, evidence of the benefit and harm associated with specific low molecular weight heparins such as enoxaparin is dated. No current systematic review and meta-analysis describing the safety and efficacy of enoxaparin for thromboembolism and thromboprophylaxis during pregnancy exists.
METHODS
PubMed, Embase, and Cochrane databases were searched on August 17, 2018 for clinical trials or observational studies in pregnant women receiving enoxaparin; patients with a prosthetic heart valve were excluded. Risk ratios (RR) with 95% confidence intervals (CI) were calculated using a random effects model, and heterogeneity was measured using the I statistic.
RESULTS
Of the 485 records identified in the search, 24 studies published clinical trials, and observational studies were found dating back to 2000. Only one observational cohort and one randomized control trial focused on the use of enoxaparin for thromboprophylaxis and therefore efficacy was not assessed; the other studies included women with recurrent pregnancy loss (15 studies), history of placental vascular complications (five studies), and recurrent in vitro fertilization failure (two studies) and were therefore analyzed in terms of safety only. Bleeding events were non-significantly more often reported for enoxaparin compared to untreated controls (RR 1.35 [0.88-2.07]) but less often reported for enoxaparin versus aspirin (RR 0.93 [0.62-1.39]); thromboembolic events, thrombocytopenia, and teratogenicity were rarely reported events; in patients with a history of recurrent pregnancy loss, encouragingly the rates of pregnancy loss were significantly lower for enoxaparin compared to untreated controls (RR 0.58 [0.34-0.96]) and enoxaparin + aspirin versus aspirin alone (RR 0.42 [0.32-0.56]) as well as observably lower for enoxaparin versus aspirin alone (RR 0.39 [0.15-1.01]), though significant heterogeneity was observed (I > 60).
CONCLUSION
Literature on the efficacy and safety of enoxaparin for thromboembolism and thromboprophylaxis remains scanty, and therefore efficacy was not assessed; in terms of safety, when including other indications for enoxaparin in pregnancy, we found that enoxaparin was associated with significantly lower complications than aspirin. Given differences in study design and study heterogeneity, pregnancy loss results should be interpreted with caution. Moreover, reports of thromboembolic events, thrombocytopenia, and congenital malformations were rare.
FUNDING
Sanofi.
Topics: Anticoagulants; Aspirin; Enoxaparin; Female; Hemorrhage; Humans; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Venous Thromboembolism
PubMed: 31673991
DOI: 10.1007/s12325-019-01124-z -
European Journal of Cardiovascular... Jan 2018Nurses are pivotal in the provision of high quality care in acute hospitals. However, the optimal dosing of the number of nurses caring for patients remains elusive. In... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Nurses are pivotal in the provision of high quality care in acute hospitals. However, the optimal dosing of the number of nurses caring for patients remains elusive. In light of this, an updated review of the evidence on the effect of nurse staffing levels on patient outcomes is required.
AIM
To undertake a systematic review and meta-analysis examining the association between nurse staffing levels and nurse-sensitive patient outcomes in acute specialist units.
METHODS
Nine electronic databases were searched for English articles published between 2006 and 2017. The primary outcomes were nurse-sensitive patient outcomes.
RESULTS
Of 3429 unique articles identified, 35 met the inclusion criteria. All were cross-sectional and the majority utilised large administrative databases. Higher staffing levels were associated with reduced mortality, medication errors, ulcers, restraint use, infections, pneumonia, higher aspirin use and a greater number of patients receiving percutaneous coronary intervention within 90 minutes. A meta-analysis involving 175,755 patients, from six studies, admitted to the intensive care unit and/or cardiac/cardiothoracic units showed that a higher nurse staffing level decreased the risk of inhospital mortality by 14% (0.86, 95% confidence interval 0.79-0.94). However, the meta-analysis also showed high heterogeneity (I=86%).
CONCLUSION
Nurse-to-patient ratios influence many patient outcomes, most markedly inhospital mortality. More studies need to be conducted on the association of nurse-to-patient ratios with nurse-sensitive patient outcomes to offset the paucity and weaknesses of research in this area. This would provide further evidence for recommendations of optimal nurse-to-patient ratios in acute specialist units.
Topics: Hospital Mortality; Hospital Units; Humans; Nurse-Patient Relations; Nursing Staff, Hospital; Personnel Staffing and Scheduling; Quality of Health Care
PubMed: 28718658
DOI: 10.1177/1474515117721561 -
The Journal of Allergy and Clinical... Apr 2022Chronic rhinosinusitis with nasal polyposis (CRSwNP) is an inflammatory condition of the upper airways. Optimal management is unclear. (Meta-Analysis)
Meta-Analysis
Comparative efficacy and safety of monoclonal antibodies and aspirin desensitization for chronic rhinosinusitis with nasal polyposis: A systematic review and network meta-analysis.
BACKGROUND
Chronic rhinosinusitis with nasal polyposis (CRSwNP) is an inflammatory condition of the upper airways. Optimal management is unclear.
OBJECTIVE
We compared the effects of mAbs and aspirin desensitization (ASA-D) for treatment of CRSwNP.
METHODS
We searched the Medline, Embase, Cochrane Central Register of Controlled Trials, International Clinical Trials Registry Platform, US Food and Drug Administration, and the European Medicines Agency databases from inception to August 4, 2021, for randomized controlled trials comparing the effects of mAbs and ASA-D for CRSwNP. We conducted network meta-analysis of sinusitis symptoms, heath-related quality of life, rescue oral corticosteroids and surgery, endoscopic and radiologic scores, and adverse events. We used the Grades of Recommendation Assessment, Development and Evaluation (GRADE) approach to assess certainty of evidence. PROSPERO CRD42020177334.
RESULTS
Twenty-nine randomized controlled trials evaluating 8 treatments (n = 3461) were included in the network meta-analysis. Compared to placebo, moderate to high certainty evidence showed that health-related quality of life (SNOT-22) improved with dupilumab (mean difference [MD] -19.91 [95% confidence interval (CI) -22.50, -17.32]), omalizumab (MD -16.09 [95% CI -19.88, -12.30]), mepolizumab (MD -12.89 [95% CI -16.58, -9.19], ASA-D (MD -10.61 [95% CI -14.51, -6.71]), and benralizumab (MD -7.68 [95% CI -12.09, -3.27]). The risk of rescue nasal polyp surgery likely decreased with dupilumab (risk difference [RD] -16.35% [95% CI -18.13, -13.48]), omalizumab (RD -7.40% [95% CI -11.04, -2.43]), mepolizumab (RD -12.33% [95% CI -15.56, -7.22]), and ASA-D (RD -16.00% [95% CI -19.79, 0.21]; all moderate certainty). Comparisons among agents show with moderate to high certainty that dupilumab ranks among the most beneficial for 7 of 7 outcomes, omalizumab for 2 of 7, mepolizumab for 1 of 7, and ASA-D for 1 of 7.
CONCLUSIONS
Multiple biologics and ASA-D credibly improve patient-important outcomes, with clinically important differences in effects among agents; dupilumab uniquely ranks among the most beneficial for all outcomes studied.
Topics: Antibodies, Monoclonal; Antineoplastic Agents, Immunological; Aspirin; Chronic Disease; Humans; Nasal Polyps; Network Meta-Analysis; Omalizumab; Quality of Life; Sinusitis
PubMed: 34543652
DOI: 10.1016/j.jaci.2021.09.009 -
Health Technology Assessment... Mar 2017Warfarin is effective for stroke prevention in atrial fibrillation (AF), but anticoagulation is underused in clinical care. The risk of venous thromboembolic disease... (Meta-Analysis)
Meta-Analysis Review
Oral anticoagulants for primary prevention, treatment and secondary prevention of venous thromboembolic disease, and for prevention of stroke in atrial fibrillation: systematic review, network meta-analysis and cost-effectiveness analysis.
BACKGROUND
Warfarin is effective for stroke prevention in atrial fibrillation (AF), but anticoagulation is underused in clinical care. The risk of venous thromboembolic disease during hospitalisation can be reduced by low-molecular-weight heparin (LMWH): warfarin is the most frequently prescribed anticoagulant for treatment and secondary prevention of venous thromboembolism (VTE). Warfarin-related bleeding is a major reason for hospitalisation for adverse drug effects. Warfarin is cheap but therapeutic monitoring increases treatment costs. Novel oral anticoagulants (NOACs) have more rapid onset and offset of action than warfarin, and more predictable dosing requirements.
OBJECTIVE
To determine the best oral anticoagulant/s for prevention of stroke in AF and for primary prevention, treatment and secondary prevention of VTE.
DESIGN
Four systematic reviews, network meta-analyses (NMAs) and cost-effectiveness analyses (CEAs) of randomised controlled trials.
SETTING
Hospital (VTE primary prevention and acute treatment) and primary care/anticoagulation clinics (AF and VTE secondary prevention).
PARTICIPANTS
Patients eligible for anticoagulation with warfarin (stroke prevention in AF, acute treatment or secondary prevention of VTE) or LMWH (primary prevention of VTE).
INTERVENTIONS
NOACs, warfarin and LMWH, together with other interventions (antiplatelet therapy, placebo) evaluated in the evidence network.
MAIN OUTCOME MEASURES
Stroke, symptomatic VTE, symptomatic deep-vein thrombosis and symptomatic pulmonary embolism. Major bleeding, clinically relevant bleeding and intracranial haemorrhage. We also considered myocardial infarction and all-cause mortality and evaluated cost-effectiveness.
DATA SOURCES
MEDLINE and PREMEDLINE In-Process & Other Non-Indexed Citations, EMBASE and The Cochrane Library, reference lists of published NMAs and trial registries. We searched MEDLINE and PREMEDLINE In-Process & Other Non-Indexed Citations, EMBASE and The Cochrane Library. The stroke prevention in AF review search was run on the 12 March 2014 and updated on 15 September 2014, and covered the period 2010 to September 2014. The search for the three reviews in VTE was run on the 19 March 2014, updated on 15 September 2014, and covered the period 2008 to September 2014.
REVIEW METHODS
Two reviewers screened search results, extracted and checked data, and assessed risk of bias. For each outcome we conducted standard meta-analysis and NMA. We evaluated cost-effectiveness using discrete-time Markov models.
RESULTS
Apixaban (Eliquis, Bristol-Myers Squibb, USA; Pfizer, USA) [5 mg bd (twice daily)] was ranked as among the best interventions for stroke prevention in AF, and had the highest expected net benefit. Edoxaban (Lixiana, Daiichi Sankyo, Japan) [60 mg od (once daily)] was ranked second for major bleeding and all-cause mortality. Neither the clinical effectiveness analysis nor the CEA provided strong evidence that NOACs should replace postoperative LMWH in primary prevention of VTE. For acute treatment and secondary prevention of VTE, we found little evidence that NOACs offer an efficacy advantage over warfarin, but the risk of bleeding complications was lower for some NOACs than for warfarin. For a willingness-to-pay threshold of > £5000, apixaban (5 mg bd) had the highest expected net benefit for acute treatment of VTE. Aspirin or no pharmacotherapy were likely to be the most cost-effective interventions for secondary prevention of VTE: our results suggest that it is not cost-effective to prescribe NOACs or warfarin for this indication.
CONCLUSIONS
NOACs have advantages over warfarin in patients with AF, but we found no strong evidence that they should replace warfarin or LMWH in primary prevention, treatment or secondary prevention of VTE.
LIMITATIONS
These relate mainly to shortfalls in the primary data: in particular, there were no head-to-head comparisons between different NOAC drugs.
FUTURE WORK
Calculating the expected value of sample information to clarify whether or not it would be justifiable to fund one or more head-to-head trials.
STUDY REGISTRATION
This study is registered as PROSPERO CRD42013005324, CRD42013005331 and CRD42013005330.
FUNDING
The National Institute for Health Research Health Technology Assessment programme.
Topics: Age Distribution; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Blood Pressure; Cost-Benefit Analysis; Electrocardiography; Female; Humans; Male; Markov Chains; Mass Screening; Models, Econometric; Network Meta-Analysis; Observational Studies as Topic; Primary Health Care; Pulse; Secondary Prevention; Sensitivity and Specificity; State Medicine; Stroke; United Kingdom; Venous Thromboembolism
PubMed: 28279251
DOI: 10.3310/hta21090