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2.
Can J Anaesth ; 2021 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-33624255

RESUMO

PURPOSE: This systematic review aimed to summarize reports of the incidence and long-term recurrence of new-onset atrial fibrillation (AF) associated with non-cardiac surgery. SOURCES: We searched CENTRAL, MEDLINE and EMBASE from inception to November 2019. We included studies that reported on the incidence of new-onset perioperative AF during hospitalization for non-cardiac surgery and/or AF recurrence in such patients following discharge. Reviewers screened articles and abstracted data independently and in duplicate. We assessed study quality by appraising methodology for collecting AF history, incident AF during hospitalization, and AF recurrence after discharge. PRINCIPAL FINDINGS: From 39,233 citations screened, 346 studies that enrolled a total of 5,829,758 patients met eligibility criteria. Only 27 studies used prospective, continuous inpatient electrocardiographic (ECG) monitoring to detect incident AF. Overall, the incidence of postoperative AF during hospitalization ranged from 0.004 to 50.3%, with a median [interquartile range] of 8.7 [3.8-15.0]%. Atrial fibrillation incidence varied with type of surgery. Prospective studies using continuous ECG monitoring reported significantly higher incidences of AF than those that did not (13.9% vs 1.9%, respectively; P < 0.001). A total of 13 studies (25,726 patients) with follow-up up to 5.4 years reported on AF recurrence following hospital discharge; only one study used a prospective systematic monitoring protocol. Recurrence rates ranged from 0 to 37.3%. CONCLUSIONS: Rates of AF incidence first detected following non-cardiac surgery and long-term AF recurrence vary markedly. Differences in the intensity of ECG monitoring and type of surgery may account for this variation. TRIAL REGISTRATION: PROSPERO (CRD42017068055); registered 1 September 2017.

4.
Can J Cardiol ; 2020 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-33271225

RESUMO

BACKGROUND: Atrial fibrillation (AF) is often detected during hospitalization for surgery or medical illness and is often assumed to be due to the acute condition. METHODS: ASSERT enrolled patients >65 years old without AF. Pacemakers or implantable cardioverter defibrillators recorded device-detected AF. We identified participants who were hospitalized and compared the prevalence of AF before and after hospitalization. RESULTS: Among 2580 participants, 436 (16.9%) had a surgical or medical hospitalization. In the 30 days following a first hospitalization, 43 participants (9.9%, 95% confidence interval [CI] 7.2%-13.1%) had >6 minutes of device-detected AF; 20 (4.6%, 95% CI 2.8%-7.0%) had >6 hours. More participants had AF >6 minutes in the 30 days following hospitalization, as compared to the period 30-60 days before hospitalization (9.9% versus 4.4%, P < 0.001). Similar results were observed for episodes >6 hours (4.6% versus 2.3%, P = 0.03). Roughly half of participants with device-detected AF in the 30 days following hospitalization had ≥1 episodes of the same duration in the 6 months prior (50% [95% CI 31.3%-68.7%] for >6 minutes; 68.8% [95% CI 41.3%-89.0%] for >6 hours). Those with AF in the 30 days following hospitalization were more likely to have had AF in the past (adjusted OR 7.2 95%CI 3.2-15.8 for episodes >6 minutes; adjusted OR 32.6, 95%CI 10.3-103.4 for >6 hours). CONCLUSIONS: The prevalence of device-detected AF increases around the time of hospitalization for non-cardiac surgery or medical illness. About half of patients with AF around the time of hospitalization previously had similar episodes.

6.
Intensive Care Med ; 2020 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-33079217

RESUMO

PURPOSE: With the publication of a large randomized-controlled trial (RCT) suggesting that tranexamic acid (TXA) may improve head-injury-related deaths, we aimed to determine the safety and efficacy of TXA in acute traumatic brain injury (TBI). METHODS: In this systematic review and meta-analysis, we searched MEDLINE, PubMed, EMBASE, CINHAL, ACPJC, Google Scholar, and unpublished sources from inception until June 24, 2020 for randomized-controlled trials comparing TXA and placebo in adults and adolescents (≥ 15 years of age) with acute TBI. We screened studies and extracted summary estimates independently and in duplicate. We assessed the quality of evidence using the grading of recommendations assessment, development, and evaluation approach. This study is registered with PROSPERO (CRD42020164232). RESULTS: Nine RCTs enrolled 14,747 patients. Compared to placebo, TXA had no effect on mortality (RR 0.95; 95% CI 0.88-1.02; RD 1.0% reduction; 95% CI 2.5% reduction to 0.4% increase, moderate certainty) or disability assessed by the Disability Rating Scale (MD, - 0.18 points; 95% CI - 0.43 to 0.08; moderate certainty). TXA may reduce hematoma expansion on subsequent imaging (RR 0.77; 95% CI 0.58-1.03, RD 3.6%, 95% CI 6.6% reduction to 0.5% increase, low certainty). Risks of adverse events (all moderate, low, or very low certainty) were similar between placebo and TXA. CONCLUSIONS: In patients with acute TBI, TXA probably has no effect on mortality or disability. TXA may decrease hematoma expansion on subsequent imaging; however, this outcome is likely of less importance to patients. The use of TXA probably does not increase the risk of adverse events.

7.
Pacing Clin Electrophysiol ; 43(11): 1373-1381, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33058175

RESUMO

BACKGROUND: Many patients undergoing cardiac device implantation are taking direct oral anticoagulation (DOAC). Continuing DOAC during device implantation may increase periprocedural bleeding risk; however, interrupting DOACs may increase thromboembolic risk. OBJECTIVE: To compare the incidence of clinically significant pocket hematoma and thromboembolism in patients who have their DOAC continued or interrupted for cardiac device implantation. METHODS: We searched MEDLINE, EMBASE, and randomized controlled trial (CENTRAL) until December 2019 and included randomized controlled trials (RCTs) and observational studies that compared outcomes after continuing or interrupting DOAC during cardiac device implantation. Independently and in duplicate, reviewers screened titles, abstracts, and full text of potentially eligible studies. They then evaluated risk of bias and abstracted data. RCT data were pooled using a fixed-effect model. Quality of evidence was assessed using grading of recommendations assessment, development and evaluation (GRADE). RESULTS: Two RCTs, representing 763 patients, and three observational studies met eligibility criteria. In RCTs, continuing DOAC for device implantation compared to interrupting DOAC resulted in no significant difference in clinically significant pocket hematoma (2.1% vs 1.8%; RR 1.15; 95% CI 0.44-3.05) or thromboembolism (0.03% vs 0.03%; RR 1.02; 95% CI 0.06-16.21). Quality of evidence for both outcomes was moderate due to imprecision. Observational studies showed similar results. CONCLUSIONS: Continuing DOACs for device implantation results in little to no difference in the incidence of clinically significant pocket hematoma or thromboembolism. Given the ease of stopping and restarting DOACs, interrupting DOACs may be the preferred strategy for most patients. However, whenever continuous therapeutic anticoagulation is desired, DOAC continuation should be preferred over bridging with parenteral anticoagulation.

8.
J Card Surg ; 2020 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-32985724

RESUMO

BACKGROUND: International guidelines currently recommend concomitant surgical ablation of atrial fibrillation (AF) in patients with AF undergoing cardiac surgery. However, a systematic review and meta-analysis of 23 randomized controlled trials (RCTs) showed no significant difference in mortality or stroke in patients who underwent surgical AF ablation compared with those who did not (moderate-quality evidence). METHODS: We estimated the Ontario-wide costs of surgical AF ablation between 2006 and 2017 using data from a systematic review and meta-analysis of RCTs, estimates of case volumes from Ontario Health Insurance Plan fee codes, the ongoing left atrial appendage occlusion study III trial (NCT01561651), institutional costs from large academic centers in Ontario, as well as professional fees based on the Ontario fee schedule. Device costs were obtained from Canadian industry data with expert input. RESULTS: We estimated the average extra cost of surgical AF ablation at $4,287 CAD (95% CI $4,113-4,619) per patient. Procedural costs (equipment costs and physician remuneration) comprise 82.2% of this, while smaller portions relate to the increased need for pacemaker (3.9%) and additional hospital length of stay (13.9%). Approximately 2,391 patients underwent surgical AF ablation between 2006 and 2017, corresponding to an estimated $10.2 million in incremental cost during that time span. CONCLUSION: Ontario taxpayers spend significant financial resources on surgical ablation of AF, a procedure lacking high-quality evidence demonstrating benefit in reducing mortality or stroke. Further large prospective studies examining clinically important outcomes are needed to justify its routine use in patient care and to guide allocation of healthcare funds.

9.
Interact Cardiovasc Thorac Surg ; 31(3): 354-363, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32772110

RESUMO

OBJECTIVES: Acetylsalicylic acid (ASA) monotherapy is the standard of care after coronary artery bypass grafting (CABG), but the benefits of more intense antiplatelet therapy, specifically dual antiplatelet therapy (DAPT), require further exploration in CABG patients. We performed a network meta-analysis to compare the effects of various antiplatelet regimens on saphenous vein graft patency, mortality, major adverse cardiovascular events and bleeding among CABG patients. METHODS: We searched Cochrane Central Register of Controlled Trials, Medical Literature Analysis and Retrieval Systems Online, Excerpta Medica Database, Cumulative Index to Nursing and Allied Health Literature, American College of Physicians Journal Club and conference proceedings for randomized controlled trials. Screening, data extraction, risk of bias assessment and Grading of Recommendations Assessment, Development and Evaluation were performed in duplicate. We conducted a random effect Bayesian network meta-analysis including both direct and indirect comparisons. RESULTS: We included 43 randomized controlled trials studying 15 511 patients. DAPT with low-dose ASA and ticagrelor [odds ratio (OR) 2.53, 95% credible interval (CrI) 1.35-4.72; I2 = 55; low certainty] or clopidogrel (OR 1.56, 95% CrI 1.02-2.39; I2 = 55; very low certainty) improved saphenous vein graft patency when compared to low-dose ASA monotherapy. DAPT with low-dose ASA and ticagrelor was associated with lower mortality (OR 0.52, 95% CrI 0.30-0.87; I2 = 14; high certainty) and lower major adverse cardiovascular events (OR 0.63, 95% CrI 0.44-0.91; I2 = 0; high certainty) when compared to low-dose ASA monotherapy. Based on moderate certainty evidence, DAPT was associated with an increase in major bleeding. CONCLUSIONS: Our results suggest that DAPT improves saphenous vein graft patency, mortality and major adverse cardiovascular event. As such, surgeons and physicians should consider re-initiating DAPT for acute coronary syndrome patients after their CABG, at the expense of an increased risk for major bleeding. CLINICAL TRIAL REGISTRATION: International Prospective Register of Systematic Reviews ID Number CRD42019127695.

10.
Artigo em Inglês | MEDLINE | ID: mdl-32803405

RESUMO

INTRODUCTION: Daily medication is the cornerstone of evidence-based therapy to reduce mortality and morbidity in patients with heart failure (HF). Up to 20% of Canadian patients pay for medications out of pocket. We sought to identify strategies that patients and prescribers can employ to reduce these costs. METHODS: We collected data from outpatient pharmacies in Hamilton, Ontario. We determined prices for different medications in each of the drug classes recommended for HF with reduced ejection fraction in the Canadian Cardiovascular Society's guidelines. We examined differences in dispensing and delivery fees and inquired about other cost-saving strategies. RESULTS: We collected data from 24 different pharmacies, including a selection of hospital-based, independent, and larger chain pharmacies. In the most extreme scenario (i.e., 90-day prescription instead of a 30-day prescription and the least expensive generic drug instead of the most expensive brand name drug), total medication costs can differ by up to $495.56 per month. Costs were affected by choice of agent within a drug class, generic versus brand-name drug, quantity dispensed, dispensing fee, and delivery cost. CONCLUSIONS: Prescription content, dispensing practice, and pharmacy choice can remarkably impact out-of-pocket costs for HF medications. Prescribers can reduce costs by writing 90-day prescriptions and choosing the lowest-cost generic drugs in each therapeutic class. Patients should consider the services received for their pharmacy dispensing fees, use free delivery services where needed, and request inexpensive generic drugs. Pharmacists can facilitate cost minimization without compromising therapeutic efficacy.

13.
Interact Cardiovasc Thorac Surg ; 31(2): 141-151, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-32642775

RESUMO

OBJECTIVES: The benefits of preoperative intravenous (IV) iron treatment in cardiac surgery patients with preoperative anaemia or iron deficiency have not been well-established. We performed a systematic review and meta-analysis to determine the effects of treating preoperative anaemia or iron deficiency with IV iron in adult cardiac surgery patients. METHODS: We searched Cochrane Central Register of Controlled Trials, Medical Literature Analysis and Retrieval Systems Online and Excerpta Medica Database for randomized controlled trials (RCTs) and observational studies comparing IV iron to oral iron or no iron. We performed title and abstract, full-text screening, data extraction and risk of bias assessment independently and in duplicate. We pooled data using a random effects model and evaluated the overall quality of evidence. RESULTS: We identified 4 RCTs and 7 observational studies. Pooled data from observational studies suggested a benefit of IV iron compared to no iron on mortality [relative risk 0.39, 95% confidence interval (CI) 0.23-0.65; P < 0.001, very low quality], units transfused per patient (mean difference -1.22, 95% CI -1.85 to -0.60; P < 0.001, very low quality), renal injury (relative risk 0.50, 95% CI 0.36-0.69; P < 0.001, very low quality) and hospital length of stay (mean difference -4.24 days, 95% CI -6.86 to -1.63; P = 0.001, very low quality). Pooled data from RCTs demonstrated a reduction in the number of patients transfused with IV iron compared to oral or no iron (relative risk 0.81, 95% CI 0.70-0.94; P = 0.005, moderate quality). The pooled estimates of effect from RCTs for mortality, hospital length of stay, units transfused per patient and renal injury were consistent in direction with observational studies. CONCLUSIONS: This meta-analysis suggests that IV iron improves postoperative morbidity in adult cardiac surgery patients with preoperative anaemia or iron deficiency. A large, rigorous, placebo-controlled, double-blinded, multicentre trial is needed to clarify the role of IV iron in this patient population. CLINICAL TRIAL REGISTRATION: International prospective register of systematic reviews ID Number CRD42019122844.

14.
Eur J Vasc Endovasc Surg ; 60(3): 469-478, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32620348

RESUMO

OBJECTIVE: In vascular and cardiac surgery, the ability to maintain haemostasis and seal haemorrhagic tissues is key. Fibrin and thrombin based sealants were introduced as a means to prevent or halt bleeding during surgery. Whether fibrin and thrombin sealants affect surgical outcomes is poorly established. A systematic review and meta-analysis was performed to examine the impact of fibrin or thrombin sealants on patient outcomes in vascular and cardiac surgery. DATA SOURCES: Cochrane CENTRAL, Embase, and MEDLINE, as well as trial registries, conference abstracts, and reference lists of included articles were searched from inception to December 2019. REVIEW METHODS: Studies comparing the use of fibrin or thrombin sealant with either an active (other haemostatic methods) or standard surgical haemostatic control in vascular and cardiac surgery were searched for. The Cochrane risk of bias tool and the ROBINS-I tool (Risk Of Bias In Non-randomised Studies - of Interventions) were used to assess the risk of bias of the included randomised and non-randomised studies; quality of evidence was assessed by the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework. Two reviewers screened studies, assessed risk of bias, and extracted data independently and in duplicate. Data from included trials were pooled using a random effects model. RESULTS: Twenty-one studies (n = 7 622 patients) were included: 13 randomised controlled trials (RCTs), five retrospective, and three prospective cohort studies. Meta-analysis of the RCTs showed a statistically significant decrease in the volume of blood lost (mean difference 120.7 mL, in favour of sealant use [95% confidence interval {CI} -150.6 - -90.7; p < .001], moderate quality). Time to haemostasis was also shown to be reduced in patients receiving sealant (mean difference -2.5 minutes [95% CI -4.0 - -1.1; p < .001], low quality). Post-operative blood transfusions, re-operation due to bleeding, and 30 day mortality were not significantly different for either RCTs or observational data. CONCLUSION: The use of fibrin and thrombin sealants confers a statistically significant but clinically small reduction in blood loss and time to haemostasis; it does not reduce blood transfusion. These Results may support selective rather than routine use of fibrin and thrombin sealants in vascular and cardiac surgery.


Assuntos
Perda Sanguínea Cirúrgica/prevenção & controle , Procedimentos Cirúrgicos Cardíacos , Adesivo Tecidual de Fibrina/administração & dosagem , Hemostasia , Hemostáticos/administração & dosagem , Hemorragia Pós-Operatória/prevenção & controle , Trombina/administração & dosagem , Adesivos Teciduais/administração & dosagem , Procedimentos Cirúrgicos Vasculares , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Adesivo Tecidual de Fibrina/efeitos adversos , Hemostáticos/efeitos adversos , Humanos , Hemorragia Pós-Operatória/etiologia , Fatores de Risco , Trombina/efeitos adversos , Fatores de Tempo , Adesivos Teciduais/efeitos adversos , Resultado do Tratamento , Procedimentos Cirúrgicos Vasculares/efeitos adversos
15.
Can J Anaesth ; 67(12): 1728-1737, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32671805

RESUMO

PURPOSE: The Impella® device is a form of mechanical circulatory support (MCS) used in critically ill adults with cardiogenic shock. We sought to evaluate short- and long-term outcomes following the use of Impella, including mortality, healthcare utilization, and costs. METHODS: Population-based, retrospective cohort study of adult patients (≥ 16 yr) receiving Impella in Ontario, Canada (1 April 2012-31March 2019). We captured outcomes through linkage to health administrative databases. The primary outcome was mortality during hospitalization. Secondary outcomes included mortality at 30 days, 90 days, and one year following Impella insertion. We analyzed health system costs in Canadian dollars in the year following the date of the index admission, including the costs of inpatient admission. RESULTS: We included 162 patients. Mean (standard deviation) age was 59.2 (14.5) yr, and 73.5% of patients were male. Median [interquartile range (IQR)] time to Impella insertion from date of hospital admission was 2 [1-9] days. In-hospital mortality was 56.8%, and a significant proportion of patients were bridged to a ventricular assist device (67.9%). Mortality at one year was 61.7%. Among hospital survivors, only 38.6% were discharged home independently. Median [IQR] total cost in the year following admission among all patients was $88,397 [32,718-225,628], of which $66,529 [22,789-183,165] was attributed to inpatient care. CONCLUSIONS: In-hospital mortality among patients with cardiogenic shock receiving Impella is high, but with minimal increase at one year. While Impella patients accrued substantial costs, these largely reflected inpatient costs, and not costs incurred following hospital discharge.

18.
J Neurotrauma ; 37(9): 1127-1139, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32024432

RESUMO

Interventions to optimize spinal cord perfusion via support of mean arterial pressure (MAP) or spinal cord perfusion pressure (SCPP) are thought to play a critical role in the management of patients with acute traumatic spinal cord injuries, but there is ongoing controversy about efficacy and safety. We aimed to determine the effects of optimizing spinal cord perfusion on neurological recovery and risks for adverse events. We searched multiple databases for published and unpublished reports. Two reviewers independently screened articles, extracted data, and evaluated risk of bias. We synthesized data and evaluated confidence in anticipated treatment effects according to the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) approach. We identified 20 eligible observational studies and 1 eligible randomized controlled trial. According to low or very low quality evidence, the effect of MAP support on neurological recovery after acute traumatic spinal cord injury is uncertain, and the use of vasopressors to support MAP may be associated with increased rates of predominantly cardiac adverse events. Increased SCPP appears likely to be associated with improved neurological recovery, but SCPP monitoring via intradural catheters at the anatomical site of injury may involve increased risks of cerebrospinal fluid leakage requiring revision surgery or pseudomeningocele. No study directly compared the effects of specific MAP goal ranges, SCPP ranges, SCPP monitoring techniques, or durations of treatment. Very low quality evidence suggests that norepinephrine may have less risk of adverse events than dopamine. The current literature is insufficient to make strong recommendations about interventions to support spinal cord perfusion via MAP or SCPP goals in patients with acute traumatic spinal cord injuries. Data are compatible with a variety of treatment decisions, and individualized approaches may be optimal. Further investigation to clarify the risks, benefits, and alternatives to MAP or SCPP support in this population is warranted.

19.
Trials ; 21(1): 92, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31941546

RESUMO

BACKGROUND: The optimal treatment duration for patients with bloodstream infection is understudied. The Bacteremia Antibiotic Length Actually Needed for Clinical Effectiveness (BALANCE) pilot randomized clinical trial (RCT) determined that it was feasible to enroll and randomize intensive care unit (ICU) patients with bloodstream infection to 7 versus 14 days of treatment, and served as the vanguard for the ongoing BALANCE main RCT. We performed this BALANCE-Ward pilot RCT to examine the feasibility and impact of potentially extending the BALANCE main RCT to include patients hospitalized on non-ICU wards. METHODS: We conducted an open pilot RCT among a subset of six sites participating in the ongoing BALANCE RCT, randomizing patients with positive non-Staphylococcus aureus blood cultures on non-ICU wards to 7 versus 14 days of antibiotic treatment. The co-primary feasibility outcomes were recruitment rate and adherence to treatment duration protocol. We compared feasibility outcomes, patient/pathogen characteristics, and overall outcomes among those enrolled in this BALANCE-Ward and prior BALANCE-ICU pilot RCTs. We estimated the sample size and non-inferiority margin impacts of expanding the BALANCE main RCT to include non-ICU patients. RESULTS: A total of 134 patients were recruited over 47 site-months (mean 2.9 patients/site-month, median 1.0, range 0.1-4.4 patients/site-month). The overall recruitment rate exceeded the BALANCE-ICU pilot RCT (mean 1.10 patients/site-month, p < 0.0001). Overall protocol adherence also exceeded the adherence in the BALANCE-ICU pilot RCT (125/134, 93% vs 89/115, 77%, p = 0.0003). BALANCE-Ward patients were older, with lower Sequential Organ Failure Assessment scores, and higher proportions of infections caused by Escherichia coli and genito-urinary sources of bloodstream infection. The BALANCE-Ward pilot RCT patients had an overall 90-day mortality rate of 17/133 (12.8%), which was comparable to the 90-day mortality rate in the ICU pilot RCT (17/115, 14.8%) (p = 0.65). Simulation models indicated there would be minimal sample size and non-inferiority margin implications of expanding enrolment to increasing proportions of non-ICU versus ICU patients. CONCLUSION: It is feasible to enroll non-ICU patients in a trial of 7 versus 14 days of antibiotics for bloodstream infection, and expanding the BALANCE RCT hospital-wide has the potential to improve the timeliness and generalizability of trial results. TRIAL REGISTRATION: Clinicaltrials.gov, NCT02917551. Registered on September 28, 2016.


Assuntos
Antibacterianos/uso terapêutico , Bacteriemia/tratamento farmacológico , Unidades de Terapia Intensiva/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Bacteriemia/microbiologia , Estudos de Casos e Controles , Protocolos Clínicos , Comorbidade , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mortalidade/tendências , Fatores de Tempo , Resultado do Tratamento
20.
Thromb Haemost ; 120(3): 484-494, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31940677

RESUMO

BACKGROUND: Western guidelines recommend an international normalized ratio (INR) range of 2 to 3 when using warfarin for stroke prevention in atrial fibrillation (AF), but lower INR ranges are frequently used in East Asia. We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) in AF patients comparing the effect of lower versus standard INR targets on thromboembolism, major bleeding, and mortality. METHODS: We searched Western databases including Cochrane CENTRAL, Medline, and Embase as well as Chinese databases including SinoMed, CNKI, and Wanfang Data. We pooled risk ratios (RRs) using random-effects model. We grouped INR targets in two ways: (1) any study-specific lower versus standard targets and (2) INR ranges of approximately 1.5 to 2 versus 2 to 3. RESULTS: Seventy-nine RCTs (n = 12,928) met eligibility criteria: 74 (n = 11,322) from East Asia and 5 (n = 1,606) from Western countries. Compared with standard targets, lower INR ranges were associated with higher rates of thromboembolism (76 RCTs, n = 12,577: 7.1% vs. 4.4%, RR 1.50, 95% confidence interval [CI] 1.29-1.74, I 2 = 0%), lower rates of major bleeding (61 RCTs, n = 10,815: 2.2% vs. 4.4%, RR 0.54, 95% CI 0.44-0.67, I 2 = 0%), and similar mortality (32 RCTs, n = 7,327: 4.8% vs. 5.2%, RR 1.00, 95% CI 0.85-1.19, I 2 = 0%). Results were similar when comparing target ranges of approximately 1.5 to 2 versus 2 to 3. CONCLUSION: Moderate quality evidence suggests lower INR targets reduce bleeding but increase thromboembolism in AF. The data are dominated by East-Asian studies, limiting generalizability to Western populations. Until higher quality data demonstrate otherwise, an INR range of 2 to 3 should remain standard for thromboembolic prophylaxis in AF.

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