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Medicina (Kaunas, Lithuania) Aug 2022Background and Objectives: Interest in artificial intelligence (AI) for outcome prediction has grown substantially in recent years. However, the prognostic role of AI... (Review)
Review
Background and Objectives: Interest in artificial intelligence (AI) for outcome prediction has grown substantially in recent years. However, the prognostic role of AI using advanced cardiac magnetic resonance imaging (CMR) remains unclear. This systematic review assesses the existing literature on AI in CMR to predict outcomes in patients with cardiovascular disease. Materials and Methods: Medline and Embase were searched for studies published up to November 2021. Any study assessing outcome prediction using AI in CMR in patients with cardiovascular disease was eligible for inclusion. All studies were assessed for compliance with the Checklist for Artificial Intelligence in Medical Imaging (CLAIM). Results: A total of 5 studies were included, with a total of 3679 patients, with 225 deaths and 265 major adverse cardiovascular events. Three methods demonstrated high prognostic accuracy: (1) three-dimensional motion assessment model in pulmonary hypertension (hazard ratio (HR) 2.74, 95%CI 1.73−4.34, p < 0.001), (2) automated perfusion quantification in patients with coronary artery disease (HR 2.14, 95%CI 1.58−2.90, p < 0.001), and (3) automated volumetric, functional, and area assessment in patients with myocardial infarction (HR 0.94, 95%CI 0.92−0.96, p < 0.001). Conclusion: There is emerging evidence of the prognostic role of AI in predicting outcomes for three-dimensional motion assessment in pulmonary hypertension, ischaemia assessment by automated perfusion quantification, and automated functional assessment in myocardial infarction.
Topics: Artificial Intelligence; Humans; Hypertension, Pulmonary; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Myocardial Infarction; Predictive Value of Tests; Prognosis; Risk Assessment
PubMed: 36013554
DOI: 10.3390/medicina58081087 -
Echocardiography (Mount Kisco, N.Y.) Dec 2021Heart failure (HF) complicating acute coronary syndrome (ACS) is a herald of adverse outcomes. In this systematic review, we investigated the prevalence of lung...
BACKGROUND
Heart failure (HF) complicating acute coronary syndrome (ACS) is a herald of adverse outcomes. In this systematic review, we investigated the prevalence of lung ultrasound (LUS) findings and their prognostic utility among patients with ACS.
METHODS
We searched the online databases PubMed, EMBASE, and Web of Science for studies (full-text articles, published in English) that used LUS in adult patients with ACS [ST-elevation myocardial infarction (STEMI), non-ST-elevation myocardial infarction (NSTEMI), and unstable angina].
RESULTS
Of 462 studies screened, five prospective, observational investigations published between 2010 and 2021 including 1087 patients met our inclusion criteria. Two studies employed 28-zone imaging protocols whereas three used eight-zone protocols. The proportion of patients with a prior HF diagnosis was ≤ 5% in all studies. The prevalence of B-lines was examined prior to or within 12 hours after coronary angiogram and reporting varied between studies due to different imaging protocols or quantification methods. A higher number of B-lines on admission was associated with an increased risk for developing symptomatic HF during the baseline hospitalization and with a higher in-hospital mortality rate using either 8 or 28-zone protocols. A higher number of B-lines at baseline was also associated with an increased risk of subsequent HF hospitalization or all-cause death.
CONCLUSIONS
Pulmonary congestion by LUS performed on admission appears to be a common finding among patients hospitalized for ACS and is associated with adverse in-hospital and long-term outcomes. Further investigations using standardized LUS protocols are warranted and have the potential to improve risk stratification in ACS.
Topics: Acute Coronary Syndrome; Adult; Humans; Lung; Prevalence; Prognosis; Prospective Studies
PubMed: 34845749
DOI: 10.1111/echo.15262 -
The Cochrane Database of Systematic... Jun 2023Following hip fracture, people sustain an acute blood loss caused by the injury and subsequent surgery. Because the majority of hip fractures occur in older adults,... (Review)
Review
BACKGROUND
Following hip fracture, people sustain an acute blood loss caused by the injury and subsequent surgery. Because the majority of hip fractures occur in older adults, blood loss may be compounded by pre-existing anaemia. Allogenic blood transfusions (ABT) may be given before, during, and after surgery to correct chronic anaemia or acute blood loss. However, there is uncertainty about the benefit-risk ratio for ABT. This is a potentially scarce resource, with availability of blood products sometimes uncertain. Other strategies from Patient Blood Management may prevent or minimise blood loss and avoid administration of ABT.
OBJECTIVES
To summarise the evidence from Cochrane Reviews and other systematic reviews of randomised or quasi-randomised trials evaluating the effects of pharmacological and non-pharmacological interventions, administered perioperatively, on reducing blood loss, anaemia, and the need for ABT in adults undergoing hip fracture surgery.
METHODS
In January 2022, we searched the Cochrane Library, MEDLINE, Embase, and five other databases for systematic reviews of randomised controlled trials (RCTs) of interventions given to prevent or minimise blood loss, treat the effects of anaemia, and reduce the need for ABT, in adults undergoing hip fracture surgery. We searched for pharmacological interventions (fibrinogen, factor VIIa and factor XIII, desmopressin, antifibrinolytics, fibrin and non-fibrin sealants and glue, agents to reverse the effects of anticoagulants, erythropoiesis agents, iron, vitamin B12, and folate replacement therapy) and non-pharmacological interventions (surgical approaches to reduce or manage blood loss, intraoperative cell salvage and autologous blood transfusion, temperature management, and oxygen therapy). We used Cochrane methodology, and assessed the methodological quality of included reviews using AMSTAR 2. We assessed the degree of overlap of RCTs between reviews. Because overlap was very high, we used a hierarchical approach to select reviews from which to report data; we compared the findings of selected reviews with findings from the other reviews. Outcomes were: number of people requiring ABT, volume of transfused blood (measured as units of packed red blood cells (PRC)), postoperative delirium, adverse events, activities of daily living (ADL), health-related quality of life (HRQoL), and mortality.
MAIN RESULTS
We found 26 systematic reviews including 36 RCTs (3923 participants), which only evaluated tranexamic acid and iron. We found no reviews of other pharmacological interventions or any non-pharmacological interventions. Tranexamic acid (17 reviews, 29 eligible RCTs) We selected reviews with the most recent search date, and which included data for the most outcomes. The methodological quality of these reviews was low. However, the findings were largely consistent across reviews. One review included 24 RCTs, with participants who had internal fixation or arthroplasty for different types of hip fracture. Tranexamic acid was given intravenously or topically during the perioperative period. In this review, based on a control group risk of 451 people per 1000, 194 fewer people per 1000 probably require ABT after receiving tranexamic acid (risk ratio (RR) 0.56, 95% confidence interval (CI) 0.46 to 0.68; 21 studies, 2148 participants; moderate-certainty evidence). We downgraded the certainty for possible publication bias. Review authors found that there was probably little or no difference in the risks of adverse events, reported as deep vein thrombosis (RR 1.16, 95% CI 0.74 to 1.81; 22 studies), pulmonary embolism (RR 1.01, 95% CI 0.36 to 2.86; 9 studies), myocardial infarction (RR 1.00, 95% CI 0.23 to 4.33; 8 studies), cerebrovascular accident (RR 1.45, 95% CI 0.56 to 3.70; 8 studies), or death (RR 1.01, 95% CI 0.70 to 1.46; 10 studies). We judged evidence from these outcomes to be moderate certainty, downgraded for imprecision. Another review, with a similarly broad inclusion criteria, included 10 studies, and found that tranexamic acid probably reduces the volume of transfused PRC (0.53 fewer units, 95% CI 0.27 to 0.80; 7 studies, 813 participants; moderate-certainty evidence). We downgraded the certainty because of unexplained high levels of statistical heterogeneity. No reviews reported outcomes of postoperative delirium, ADL, or HRQoL. Iron (9 reviews, 7 eligible RCTs) Whilst all reviews included studies in hip fracture populations, most also included other surgical populations. The most current, direct evidence was reported in two RCTs, with 403 participants with hip fracture; iron was given intravenously, starting preoperatively. This review did not include evidence for iron with erythropoietin. The methodological quality of this review was low. In this review, there was low-certainty evidence from two studies (403 participants) that there may be little or no difference according to whether intravenous iron was given in: the number of people who required ABT (RR 0.90, 95% CI 0.73 to 1.11), the volume of transfused blood (MD -0.07 units of PRC, 95% CI -0.31 to 0.17), infection (RR 0.99, 95% CI 0.55 to 1.80), or mortality within 30 days (RR 1.06, 95% CI 0.53 to 2.13). There may be little or no difference in delirium (25 events in the iron group compared to 26 events in control group; 1 study, 303 participants; low-certainty evidence). We are very unsure whether there was any difference in HRQoL, since it was reported without an effect estimate. The findings were largely consistent across reviews. We downgraded the evidence for imprecision, because studies included few participants, and the wide CIs indicated possible benefit and harm. No reviews reported outcomes of cognitive dysfunction, ADL, or HRQoL.
AUTHORS' CONCLUSIONS
Tranexamic acid probably reduces the need for ABT in adults undergoing hip fracture surgery, and there is probably little or no difference in adverse events. For iron, there may be little or no difference in overall clinical effects, but this finding is limited by evidence from only a few small studies. Reviews of these treatments did not adequately include patient-reported outcome measures (PROMS), and evidence for their effectiveness remains incomplete. We were unable to effectively explore the impact of timing and route of administration between reviews. A lack of systematic reviews for other types of pharmacological or any non-pharmacological interventions to reduce the need for ABT indicates a need for further evidence syntheses to explore this. Methodologically sound evidence syntheses should include PROMS within four months of surgery.
Topics: Humans; Aged; Tranexamic Acid; Erythrocyte Transfusion; Emergence Delirium; Systematic Reviews as Topic; Hip Fractures; Hemorrhage; Anemia; Iron
PubMed: 37294864
DOI: 10.1002/14651858.CD013737.pub2 -
World Journal of Cardiology Jun 2023ST-elevation myocardial infarction (STEMI) is the result of transmural ischemia of the myocardium and is associated with a high mortality rate. Primary percutaneous...
BACKGROUND
ST-elevation myocardial infarction (STEMI) is the result of transmural ischemia of the myocardium and is associated with a high mortality rate. Primary percutaneous coronary intervention (PPCI) is the recommended first-line treatment strategy for patients with STEMI. The timely delivery of PPCI became extremely challenging for STEMI patients during the coronavirus disease 2019 (COVID-19) pandemic, leading to a projected steep rise in mortality. These delays were overcome by the shift from first-line therapy and the development of modern fibrinolytic-based reperfusion. It is unclear whether fibrinolytic-based reperfusion therapy is effective in improving STEMI endpoints.
AIM
To determine the incidence of fibrinolytic therapy during the COVID-19 pandemic and its effects on STEMI clinical outcomes.
METHODS
PubMed, Google Scholar, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials were queried from January 2020 up to February 2022 to identify studies investigating the effect of fibrinolytic therapy on the prognostic outcome of STEMI patients during the pandemic. Primary outcomes were the incidence of fibrinolysis and the risk of all-cause mortality. Data were meta-analyzed using the random effects model to derive odds ratios (OR) and 95% confidence intervals. Quality assessment was carried out using the Newcastle-Ottawa scale.
RESULTS
Fourteen studies including 50136 STEMI patients ( = 15142 in the pandemic arm; = 34994 in the pre-pandemic arm) were included. The mean age was 61 years; 79% were male, 27% had type 2 diabetes, and 47% were smokers. Compared with the pre-pandemic period, there was a significantly increased overall incidence of fibrinolysis during the pandemic period [OR: 1.80 (1.18 to 2.75); = 78%; = 0.00; GRADE: Very low]. The incidence of fibrinolysis was not associated with the risk of all-cause mortality in any setting. The countries with a low-and middle-income status reported a higher incidence of fibrinolysis [OR: 5.16 (2.18 to 12.22); = 81%; = 0.00; GRADE: Very low] and an increased risk of all-cause mortality in STEMI patients [OR: 1.16 (1.03 to 1.30); = 0%; = 0.01; GRADE: Very low]. Meta-regression analysis showed a positive correlation of hyperlipidemia ( = 0.001) and hypertension ( < 0.001) with all-cause mortality.
CONCLUSION
There is an increased incidence of fibrinolysis during the pandemic period, but it has no effect on the risk of all-cause mortality. The low- and middle-income status has a significant impact on the all-cause mortality rate and the incidence of fibrinolysis.
PubMed: 37397830
DOI: 10.4330/wjc.v15.i6.309 -
Medicine Dec 2021Long term management of patients with stable coronary artery disease of >1 year after myocardial infarction (MI) or percutaneous coronary intervention and atrial... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Long term management of patients with stable coronary artery disease of >1 year after myocardial infarction (MI) or percutaneous coronary intervention and atrial fibrillation is unclear. Current guidelines recommend using oral anti-coagulation (OAC) alone although the recommendation is weak and there is low quality evidence. Two new randomized control trials (RCTs) were published recently. We conducted an updated meta-analysis to evaluate the effect of these studies on patient outcomes.
OBJECTIVE
To conduct a systematic review and meta-analysis of published RCTs and observational studies to compare OAC alone versus OAC plus single anti-platelet therapy.
METHODS
Electronic searches were conducted using appropriate terms from 3 databases. Relevant studies included. Data extracted and analysis were performed using STATA.
MEASUREMENTS
Summary statistics were pooled and measured for primary and secondary outcomes of both treatment arms.
MAIN RESULTS
Eight studies involving 10,120 patients were included for the analysis. Five thousand two hundred thirty-seven patients were on combination therapy while 4883 were on OAC alone. There was no statistically significant difference in the primary outcome of major adverse cardiac events (hazard ratio [HR] 1.067; 95% confidence interval [CI] 0.912-1.249; P value .417). There was no statistically significant difference even in the measured secondary outcomes namely all cause mortality (HR 1.048; 95% CI 0.830-1.323; P value .695), cardiovascular mortality (HR 0.863; 95% CI 0.593-1.254; P value .439). However, we found statistically significant difference between the 2 groups in the incidence of MI with higher incidence in mono therapy group (HR 1.229; 95% CI 1.011-1.495; P value .039) and higher incidence of major bleeding in the combination therapy group in the subgroup analysis (HR 0.649; 95% CI 0.464-0.907; P value .011).
CONCLUSION
We found no reduction of major adverse cardiac event between combination therapy and mono therapy. Although mono therapy showed increased risk of major bleeding overall, subgroup analysis of the RCTs showed increased risk of major bleeding in the combination therapy group. MI was higher in the mono therapy group compared to the combination therapy group, however this outcome was not reproducible in the subgroup analysis of the RCTs.
Topics: Anticoagulants; Atrial Fibrillation; Coronary Artery Disease; Hemorrhage; Humans; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Thrombosis
PubMed: 35049165
DOI: 10.1097/MD.0000000000027498 -
International Journal of Cardiology Sep 2021Cardiopulmonary exercise test (CPET) is indicated as part of the assessment in hypertrophic cardiomyopathy (HCM) patients and stress echocardiography is often used to...
BACKGROUND
Cardiopulmonary exercise test (CPET) is indicated as part of the assessment in hypertrophic cardiomyopathy (HCM) patients and stress echocardiography is often used to assess symptoms. However, the role of exercise testing for prognostic stratification in HCM is still not established.
AIMS
To systematically review the evidence on the role of exercise testing for prognostic stratification in hypertrophic cardiomyopathy.
METHODS
A systematic review was conducted for eligible publications, between 2010 and 2020, that included evaluation of outcomes and prognosis. In these studies, patients underwent exercise echocardiography and/or cardiopulmonary exercise testing, performed according to predefined protocols. Diverse parameters were assessed in order to determine which were relevant for the prognosis. Analyzed outcomes included death from any cause, sudden cardiac death (SCD) and equivalents, cardiovascular death, heart failure requiring hospitalization or progression to New York Heart Association classes III or IV, cardiac transplantation, non-sustained ventricular tachycardia, stroke, myocardial infarction and invasive septal reduction therapy.
RESULTS
Eighteen publications were included, corresponding to a total of 7525 patients. The mean follow-up period varied between 1 and 8 years. The main findings of these studies revealed that the major predictors of outcomes were abnormal heart rate recovery, abnormal blood pressure response exercise induced wall motion abnormalities, lower peak VO2, higher VE/VCO2, and pulmonary hypertension/exercise-induced pulmonary hypertension.
CONCLUSION
Although most studies concluded that exercise test results are useful to determine prognosis in HCM, further investigation is needed regarding whether it adds independent value to the current risk stratification strategies.
Topics: Cardiomyopathy, Hypertrophic; Death, Sudden, Cardiac; Echocardiography; Exercise Test; Humans; Prognosis
PubMed: 34214502
DOI: 10.1016/j.ijcard.2021.06.051 -
The American Journal of Surgical... May 2021Coronavirus Disease 2019 (COVID-19), caused by the novel Severe Acute Respiratory Syndrome-associated Coronavirus 2 (SARS-CoV-2), has become a global threat to public... (Meta-Analysis)
Meta-Analysis
Coronavirus Disease 2019 (COVID-19), caused by the novel Severe Acute Respiratory Syndrome-associated Coronavirus 2 (SARS-CoV-2), has become a global threat to public health. COVID-19 is more pathogenic and infectious than the prior 2002 pandemic caused by SARS-CoV-1. The pathogenesis of certain disease manifestations in COVID-19 such as diffuse alveolar damage (DAD) are thought to be similar to SARS-CoV-1. However, the exact pathogenesis of COVID-19 related deaths remains poorly understood. The aim of this article was to systematically summarize the rapidly emerging literature regarding COVID-19 autopsies. A meta-analysis was also conducted based on data accrued from preprint and published articles on COVID-19 (n=241 patients) and the results compared with postmortem findings associated with SARS-CoV-1 deaths (n=91 patients). Both autopsy groups included mostly adults of median age 70 years with COVID-19 and 50 years with SARS-CoV-1. Overall, prevalence of DAD was more common in SARS-CoV-1 (100.0%) than COVID-19 (80.9%) autopsies (P=0.001). Extrapulmonary findings among both groups were not statistically significant except for hepatic necrosis (P <0.001), splenic necrosis (P<0.006) and white pulp depletion (P <0.001) that were more common with SARS-CoV-1. Remarkable postmortem findings in association with COVID-19 apart from DAD include pulmonary hemorrhage, viral cytopathic effect within pneumocytes, thromboembolism, brain infarction, endotheliitis, acute renal tubular damage, white pulp depletion of the spleen, cardiac myocyte necrosis, megakaryocyte recruitment, and hemophagocytosis.
Topics: Autopsy; Brain; COVID-19; Case-Control Studies; Global Health; Humans; Kidney; Lung; Myocardium; Severe Acute Respiratory Syndrome; Spleen
PubMed: 33481385
DOI: 10.1097/PAS.0000000000001650 -
Harm Reduction Journal Nov 2020Electronic cigarettes (e-cigarettes) are widely promoted as harm-reduction products for smokers, and smokers commonly perceive them as less harmful than combustible... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Electronic cigarettes (e-cigarettes) are widely promoted as harm-reduction products for smokers, and smokers commonly perceive them as less harmful than combustible cigarettes. One of the key questions regarding public health consequences of e-cigarettes is the magnitude of harm reduction achievable by smokers who switch from combustible cigarettes to e-cigarettes. We conducted a systematic literature review of epidemiological studies that estimated odds of respiratory and cardiovascular outcomes among former smokers who use e-cigarettes compared to current smokers.
METHODS
This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) statement. We searched the PubMed and Embase databases in September 2020 to identify epidemiological studies that compared odds of cardiovascular and respiratory outcomes among former smokers who transitioned to e-cigarettes relative to odds among current smokers not using e-cigarettes (current exclusive smokers). We included studies that provided direct estimates of relevant odds ratios (ORs). We also included studies where indirect estimates of relevant ORs could be calculated based on published results. Two reviewers independently extracted data and conducted quality appraisals.
RESULTS
Six population-based studies with sample sizes ranging from 19,475 to 161,529 respondents met review inclusion criteria, five of which were cross-sectional and one longitudinal. Three studies reported respiratory outcomes and three reported cardiovascular outcomes. ORs of respiratory outcomes (including chronic obstructive pulmonary disease, chronic bronchitis, emphysema, asthma, and wheezing) in former smokers who transitioned to e-cigarettes versus current exclusive smokers were below 1.0, ranging from 0.58 (95%CI 0.36-0.94) to 0.66 (95%CI 0.50-0.87; all p < 0.05). All ORs for cardiovascular outcomes (including stroke, myocardial infarction, and coronary heart disease) did not differ significantly from 1.0.
CONCLUSION
Though our review included a small number of studies, it provided consistent results. Former smokers who transitioned to e-cigarettes showed ~ 40% lower odds of respiratory outcomes compared to current exclusive smokers. Switching from smoking to e-cigarette does not appear to significantly lower odds of cardiovascular outcomes. Since the utility of cross-sectional studies for causal inference remains limited, both randomized controlled trials and prospective cohort studies are needed to better evaluate contributions of e-cigarettes as harm reduction tools for smokers.
Topics: Cardiovascular Diseases; Cross-Sectional Studies; Electronic Nicotine Delivery Systems; Heart Disease Risk Factors; Humans; Prospective Studies; Risk Factors; Smokers; Vaping
PubMed: 33228671
DOI: 10.1186/s12954-020-00440-w -
ESC Heart Failure Aug 2019This study aims to assess the usefulness of strain-encoded magnetic resonance (SENC) for the quantification of myocardial deformation ('strain') in healthy volunteers...
This study aims to assess the usefulness of strain-encoded magnetic resonance (SENC) for the quantification of myocardial deformation ('strain') in healthy volunteers and for the diagnostic workup of patients with different cardiovascular pathologies. SENC was initially described in the year 2001. Since then, the SENC sequence has undergone several technical developments, aiming at the detection of strain during single-heartbeat acquisitions (fast-SENC). Experimental and clinical studies that used SENC and fast-SENC or compared SENC with conventional cine or tagged magnetic resonance in phantoms, animals, healthy volunteers, or patients were systematically searched for in PubMed. Using 'strain-encoded magnetic resonance and SENC' as keywords, three phantom and three animal studies were identified, along with 27 further clinical studies, involving 185 healthy subjects and 904 patients. SENC (i) enabled reproducible assessment of myocardial deformation in vitro, in animals and in healthy volunteers, (ii) showed high reproducibility and substantially lower time spent compared with conventional tagging, (iii) exhibited incremental value to standard cine imaging for the detection of inducible ischaemia and for the risk stratification of patients with ischaemic heart disease, and (iv) enabled the diagnostic classification of patients with transplant vasculopathy, cardiomyopathies, pulmonary hypertension, and diabetic heart disease. SENC has the potential to detect a wide range of myocardial diseases early, accurately, and without the need of contrast agent injection, possibly enabling the initiation of specific cardiac therapies during earlier disease stages. Its one-heartbeat acquisition mode during free breathing results in shorter cardiovascular magnetic resonance protocols, making its implementation in the clinical realm promising.
Topics: Animals; Cardiac Imaging Techniques; Cardiomyopathies; Coronary Artery Disease; Heart; Humans; Magnetic Resonance Imaging; Myocardial Infarction
PubMed: 31021534
DOI: 10.1002/ehf2.12442 -
The Cochrane Database of Systematic... Jan 2024Hip and knee replacement surgery is a well-established means of improving quality of life, but is associated with a significant risk of bleeding. One-third of people are... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Hip and knee replacement surgery is a well-established means of improving quality of life, but is associated with a significant risk of bleeding. One-third of people are estimated to be anaemic before hip or knee replacement surgery; coupled with the blood lost during surgery, up to 90% of individuals are anaemic postoperatively. As a result, people undergoing orthopaedic surgery receive 3.9% of all packed red blood cell transfusions in the UK. Bleeding and the need for allogeneic blood transfusions has been shown to increase the risk of surgical site infection and mortality, and is associated with an increased duration of hospital stay and costs associated with surgery. Reducing blood loss during surgery may reduce the risk of allogeneic blood transfusion, reduce costs and improve outcomes following surgery. Several pharmacological interventions are available and currently employed as part of routine clinical care.
OBJECTIVES
To determine the relative efficacy of pharmacological interventions for preventing blood loss in elective primary or revision hip or knee replacement, and to identify optimal administration of interventions regarding timing, dose and route, using network meta-analysis (NMA) methodology.
SEARCH METHODS
We searched the following databases for randomised controlled trials (RCTs) and systematic reviews, from inception to 18 October 2022: CENTRAL (the Cochrane Library), MEDLINE (Ovid), Embase (Ovid), CINAHL (EBSCOhost), Transfusion Evidence Library (Evidentia), ClinicalTrials.gov and WHO International Clinical Trials Registry Platform (ICTRP).
SELECTION CRITERIA
We included RCTs of people undergoing elective hip or knee surgery only. We excluded non-elective or emergency procedures, and studies published since 2010 that had not been prospectively registered (Cochrane Injuries policy). There were no restrictions on gender, ethnicity or age (adults only). We excluded studies that used standard of care as the comparator. Eligible interventions included: antifibrinolytics (tranexamic acid (TXA), aprotinin, epsilon-aminocaproic acid (EACA)), desmopressin, factor VIIa and XIII, fibrinogen, fibrin sealants and non-fibrin sealants.
DATA COLLECTION AND ANALYSIS
We performed the review according to standard Cochrane methodology. Two authors independently assessed trial eligibility and risk of bias, and extracted data. We assessed the certainty of the evidence using CINeMA. We presented direct (pairwise) results using RevMan Web and performed the NMA using BUGSnet. We were interested in the following primary outcomes: need for allogenic blood transfusion (up to 30 days) and all-cause mortality (deaths occurring up to 30 days after the operation), and the following secondary outcomes: mean number of transfusion episodes per person (up to 30 days), re-operation due to bleeding (within seven days), length of hospital stay and adverse events related to the intervention received.
MAIN RESULTS
We included a total of 102 studies. Twelve studies did not report the number of included participants; the other 90 studies included 8418 participants. Trials included more women (64%) than men (36%). In the NMA for allogeneic blood transfusion, we included 47 studies (4398 participants). Most studies examined TXA (58 arms, 56%). We found that TXA, given intra-articularly and orally at a total dose of greater than 3 g pre-incision, intraoperatively and postoperatively, ranked the highest, with an anticipated absolute effect of 147 fewer blood transfusions per 1000 people (150 fewer to 104 fewer) (53% chance of ranking 1st) within the NMA (risk ratio (RR) 0.02, 95% credible interval (CrI) 0 to 0.31; moderate-certainty evidence). This was followed by TXA given orally at a total dose of 3 g pre-incision and postoperatively (RR 0.06, 95% CrI 0.00 to 1.34; low-certainty evidence) and TXA given intravenously and orally at a total dose of greater than 3 g intraoperatively and postoperatively (RR 0.10, 95% CrI 0.02 to 0.55; low-certainty evidence). Aprotinin (RR 0.59, 95% CrI 0.36 to 0.96; low-certainty evidence), topical fibrin (RR 0.86, CrI 0.25 to 2.93; very low-certainty evidence) and EACA (RR 0.60, 95% CrI 0.29 to 1.27; very low-certainty evidence) were not shown to be as effective compared with TXA at reducing the risk of blood transfusion. We were unable to perform an NMA for our primary outcome all-cause mortality within 30 days of surgery due to the large number of studies with zero events, or because the outcome was not reported. In the NMA for deep vein thrombosis (DVT), we included 19 studies (2395 participants). Most studies examined TXA (27 arms, 64%). No studies assessed desmopressin, EACA or topical fibrin. We found that TXA given intravenously and orally at a total dose of greater than 3 g intraoperatively and postoperatively ranked the highest, with an anticipated absolute effect of 67 fewer DVTs per 1000 people (67 fewer to 34 more) (26% chance of ranking first) within the NMA (RR 0.16, 95% CrI 0.02 to 1.43; low-certainty evidence). This was followed by TXA given intravenously and intra-articularly at a total dose of 2 g pre-incision and intraoperatively (RR 0.21, 95% CrI 0.00 to 9.12; low-certainty evidence) and TXA given intravenously and intra-articularly, total dose greater than 3 g pre-incision, intraoperatively and postoperatively (RR 0.13, 95% CrI 0.01 to 3.11; low-certainty evidence). Aprotinin was not shown to be as effective compared with TXA (RR 0.67, 95% CrI 0.28 to 1.62; very low-certainty evidence). We were unable to perform an NMA for our secondary outcomes pulmonary embolism, myocardial infarction and CVA (stroke) within 30 days, mean number of transfusion episodes per person (up to 30 days), re-operation due to bleeding (within seven days), or length of hospital stay, due to the large number of studies with zero events, or because the outcome was not reported by enough studies to build a network. There are 30 ongoing trials planning to recruit 3776 participants, the majority examining TXA (26 trials).
AUTHORS' CONCLUSIONS
We found that of all the interventions studied, TXA is probably the most effective intervention for preventing bleeding in people undergoing hip or knee replacement surgery. Aprotinin and EACA may not be as effective as TXA at preventing the need for allogeneic blood transfusion. We were not able to draw strong conclusions on the optimal dose, route and timing of administration of TXA. We found that TXA given at higher doses tended to rank higher in the treatment hierarchy, and we also found that it may be more beneficial to use a mixed route of administration (oral and intra-articular, oral and intravenous, or intravenous and intra-articular). Oral administration may be as effective as intravenous administration of TXA. We found little to no evidence of harm associated with higher doses of tranexamic acid in the risk of DVT. However, we are not able to definitively draw these conclusions based on the trials included within this review.
Topics: Male; Female; Adult; Humans; Tranexamic Acid; Aprotinin; Deamino Arginine Vasopressin; Network Meta-Analysis; Hemorrhage; Aminocaproic Acid; Stroke; Orthopedic Procedures; Fibrin
PubMed: 38226724
DOI: 10.1002/14651858.CD013295.pub2