Showing papers by "Alfonso Tafur published in 2019"

Perioperative Management of Patients With Atrial Fibrillation Receiving a Direct Oral Anticoagulant

Abstract: Importance Patients with atrial fibrillation (AF) who use a direct oral anticoagulant (DOAC) and request elective surgery or procedure present a common clinical situation yet perioperative management is uncertain. Objective To investigate the safety of a standardized perioperative DOAC management strategy. Design, Setting, and Participants The Perioperative Anticoagulation Use for Surgery Evaluation (PAUSE) cohort study conducted at 23 clinical centers in Canada, the United States, and Europe enrolled and screened patients from August 1, 2014, through July 31, 2018. Participants (n = 3007) had AF; were 18 years of age or older; were long-term users of apixaban, dabigatran etexilate, or rivaroxaban; were scheduled for an elective surgery or procedure; and could adhere to the DOAC therapy interruption protocol. Interventions A simple standardized perioperative DOAC therapy interruption and resumption strategy based on DOAC pharmacokinetic properties, procedure-associated bleeding risk, and creatinine clearance levels. The DOAC regimens were omitted for 1 day before a low–bleeding-risk procedure and 2 days before a high–bleeding-risk procedure. The DOAC regimens were resumed 1 day after a low–bleeding-risk procedure and 2 to 3 days after a high–bleeding-risk procedure. Follow-up of patients occurred for 30 days after the operation. Main Outcomes and Measures Major bleeding and arterial thromboembolism (ischemic stroke, systemic embolism, and transient ischemic attack) and the proportion of patients with an undetectable or minimal residual anticoagulant level ( Results The 3007 patients with AF (mean [SD] age of 72.5 [9.39] years; 1988 men [66.1%]) comprised 1257 (41.8%) in the apixaban cohort, 668 (22.2%) in the dabigatran cohort, and 1082 (36.0%) in the rivaroxaban cohort; 1007 patients (33.5%) had a high–bleeding-risk procedure. The 30-day postoperative rate of major bleeding was 1.35% (95% CI, 0%-2.00%) in the apixaban cohort, 0.90% (95% CI, 0%-1.73%) in the dabigatran cohort, and 1.85% (95% CI, 0%-2.65%) in the rivaroxaban cohort. The rate of arterial thromboembolism was 0.16% (95% CI, 0%-0.48%) in the apixaban cohort, 0.60% (95% CI, 0%-1.33%) in the dabigatran cohort, and 0.37% (95% CI, 0%-0.82%) in the rivaroxaban cohort. In patients with a high–bleeding-risk procedure, the rates of major bleeding were 2.96% (95% CI, 0%-4.68%) in the apixaban cohort and 2.95% (95% CI, 0%-4.76%) in the rivaroxaban cohort. Conclusions and Relevance In this study, patients with AF who had DOAC therapy interruption for elective surgery or procedure, a perioperative management strategy without heparin bridging or coagulation function testing was associated with low rates of major bleeding and arterial thromboembolism.

Venous thromboembolism prophylaxis using the Caprini score.

Abstract: Venous thromboembolism (VTE) including pulmonary embolism (PE) and deep vein thrombosis (DVT) is one of the leading causes of preventable cardiovascular disease in the United States (US) and is the number one preventable cause of death following a surgical procedure. Post-operative VTE is associated with multiple short and long-term complications. We will focus on reviewing the many faces of VTE in detail as they represent common challenging scenarios in clinical practice.

Direct Oral Factor Xa Inhibitors for the Treatment of Acute Cancer-Associated Venous Thromboembolism: A Systematic Review and Network Meta-analysis.

Abstract: Objective To explore the efficacy and safety of direct oral factor Xa inhibitors in the treatment of cancer-associated acute venous thromboembolism (VTE). Patients and Methods MEDLINE, CENTRAL (Cochrane Central Register of Controlled Trials), and Embase databases were searched for trials comparing direct oral anticoagulants (DOACs) to dalteparin for the management of cancer-associated acute VTE. Databases were searched from inception to September 19, 2018. A network meta-analysis using both frequentist and Bayesian methods was performed to analyze VTE recurrence and major and clinically relevant nonmajor bleeding. Results We identified 3 randomized controlled trials, at low risk of bias, that enrolled 1739 patients with cancer-associated VTE. Direct comparison revealed a lower rate of VTE recurrence in DOAC compared with dalteparin groups (odds ratio [OR], 0.48; 95% CI, 0.24-0.96; I2=46%). Indirect comparison suggested that apixaban had greater reduction in VTE recurrence compared with dalteparin (OR, 0.10; 95% CI, 0.01-0.82) but not rivaroxaban or edoxaban. Apixaban also had the highest probability of being ranked most effective. By direct comparisons, there was an increased likelihood of major bleeding in the DOAC group compared with dalteparin (OR, 1.70; 95% CI, 1.04-2.78). Clinically relevant nonmajor bleeding did not differ. Indirect estimates were imprecise. Subgroup analyses in gastrointestinal cancers suggested that dalteparin may have the lowest risk of bleeding, whereas estimates in urothelial cancer were imprecise. Conclusion Direct oral anticoagulants appear to lower the risk of VTE recurrence compared with dalteparin while increasing major bleeding. Apixaban may be associated with the lowest risk of VTE recurrence compared with the other DOACs.

Factor Xa Inhibitory Profile of Apixaban, Betrixaban, Edoxaban, and Rivaroxaban Does Not Fully Reflect Their Biologic Spectrum.

Abstract: The currently available oral anti-Xa agents are claimed to produce their anticoagulant and antithrombotic effects solely by the inhibition of factor Xa. This study profiled various anti-Xa drugs in routinely used laboratory assays to demonstrate that their effects are not solely related to the anti-Xa activities. Apixaban, betrixaban, edoxaban, and rivaroxaban were obtained commercially. Native and citrated whole blood was used for the activated clotting time (ACT) and thromboelastography (TEG). Citrated plasma was used for monitoring the prothrombin time (PT), activated partial thromboplastin time (aPTT), Heptest, and prothrombinase-induced clotting time (PiCT) tests. An amidolytic method was used for the determination of anti-Xa effects. Thrombin-induced fibrinokinetics was monitored optically. Thrombin generation studies were carried out using the calibrated automated thrombogram. All of the anti-Xa agents produced concentration- and assay-dependent effects. In the ACT at 2.5 μg/mL and TEG at 1.0 μg/mL, edoxaban exhibited the strongest anticoagulation effect. In the PiCT, PT, and aPTT assay at 1 μg/mL, edoxaban showed stronger effects than other agents. The half maximal inhibitory concentration of these agents for the inhibition of factor Xa ranged from 340 to >1000 ng/mL. In the thrombin generation inhibition assay, apixaban showed the strongest activity. In the fibrinokinetics, different anti-Xa agents produced varying degrees of inhibition. These results demonstrate that the measured anti-Xa activity alone does not fully reflect the overall biologic spectrum of these agents.

Reversal of Factor Xa Inhibitors by Andexanet Alfa May Increase Thrombogenesis Compared to Pretreatment Values.

Abstract: Recombinant coagulation factor Xa (FXa), inactivated Zh-zo, also known as andexanet alfa (AA), is a modified version of human FXa that has been developed to neutralize FXa inhibitors We studied the reversal effect of AA for these inhibitors in various anticoagulant and thrombin generation (TG) assays Individual aliquots of normal human plasma containing 1 µg/mL of apixaban, betrixaban, edoxaban, and rivaroxaban, were supplemented with saline or AA at a concentration of 100 µg/mL Clotting profiles include prothrombinase-induced clotting time, activated partial thromboplastin time, and prothrombin time Factor Xa activity was measured using an amidolytic method Thrombin generation was measured using a calibrated automated thrombogram Differential neutralization of all 4 anticoagulants was noted in the activated clotting time and other clotting tests The FXa activity reversal profile varied with an observed decrease in apixaban (22%), betrixaban (56%), edoxaban (28%), and rivaroxaban (49%) Andexanet alfa also led to an increased TG in comparison to saline The peak thrombin was higher (40%), area under the curve (AUC) increased (15%), whereas the lag time (LT) decreased (17%) Andexanet alfa added at 100 µg/mL to various FXa supplemented systems resulted in reversal of the inhibitory effects, restoring the TG profile; AUC, LT, and peak thrombin levels were comparable to those of unsupplemented samples Andexanet alfa is capable of reversing anti-Xa activity of different oral FXa inhibitors but overshoots thrombogenesis in both the saline and FXa inhibitor supplemented systems The degree of neutralization of Xa inhibitor is specific to each agent

Prediction of early mortality in patients with cancer-associated thrombosis in the RIETE Database.

Abstract: BACKGROUND Proper risk stratification of patients for early mortality after cancer-associated thrombosis may lead to personalized anticoagulation protocols. Therefore, we aimed to derive and validate a scoring system to predict early mortality in this population. To this end, we selected patients with active cancer and thrombosis from the Computerized Registry of Patients with Venous Thromboembolism database. METHODS The main outcome was all cause mortality within the month following a thrombotic event. We used a simple random selection to split are data in a derivation and a validation cohort. In the derivation cohort, we used recursive partitioning and binary logistic regression to identify groups at risk and to determine the likelihood of the primary outcome. The risk score was developed based on odds ratios from the final multivariate model, and then tested in the validation cohort. RESULTS In 10,025 eligible patients, we identified 6 predictors of 30-day mortality: leukocytosis ≥11.5x109/L; platelet count ≤160x109/L, metastasis, recent immobility, initial presentation as pulmonary embolism and Body Mass Index <18.5. The model divided the population into 3 risk categories: low (score 0-3), moderate (score 4-6), and high (score ≥7). The AUC for the overall score was 0.74, and using a cutoff ≥7 points, the model had a negative predictive value of 94.4%, a positive predictive value of 23.1%, a sensitivity of 73.3%, and a specificity of 64.6% in the validation cohort. CONCLUSIONS Our validated risk model may assist physicians in the selection of patients for outpatient management, and perhaps anticoagulant, considering expanding anticoagulation options.

Venous Thromboembolism in Patients with Liver Cirrhosis: Findings from the RIETE (Registro Informatizado de la Enfermedad TromboEmbolica) Registry.

Abstract: Patients with cirrhosis are not only at an increased risk of bleeding but also at risk of venous thromboembolism (VTE). We sought to determine the clinical characteristics, management, and outcomes after VTE in patients with cirrhosis. We used the data from RIETE (Registro Informatizado de la Enfermedad TromboEmbolica), an international registry of patients with VTE, to compare the outcomes in patients with and without cirrhosis. Main outcomes included all-cause mortality, pulmonary embolism (PE)-related mortality, recurrent VTE, and bleeding. Among 43,611 patients with acute VTE, 187 (0.4%) had cirrhosis. Of these, 184 (98.4%) received anticoagulation for a median of 109 days (interquartile range [IQR]: 43-201 days), most commonly with enoxaparin (median dose: 1.77 [IQR: 1.38-2.00] mg/kg/day). Compared with patients without cirrhosis, those with cirrhosis had a higher rate of all-cause mortality (10.7 vs. 3.4%; odds ratio [OR]: 3.41; 95% confidence interval [CI]: 2.03-5.46) and fatal bleeding (2.1 vs. 0.2%; OR: 13.94; 95% CI: 3.65-37.90) but similar rates of fatal PE (0.5 vs. 0.5%; OR: 1.17; 95% CI: 0.03-6.70). Patients with cirrhosis had a higher rate of all-cause mortality per 100 patient-years of follow-up (58.9 vs. 16.0; hazard ratio [HR]: 3.70; 95% CI: 2.69-4.91). One-year hazard ratio of clinically relevant bleeding (HR: 2.86; 95% CI: 1.91-4.27), fatal bleeding (HR: 8.51; 95% CI: 3.5-20.7), or recurrent VTE (HR: 2.08; 95% CI: 1.00-4.36) was higher in patients with cirrhosis. Cirrhosis is a challenging comorbidity in patients with VTE. Most patients were treated with anticoagulation and had an elevated risk of recurrence, similar risk of fatal PE, and a very high risk of bleeding including fatal bleeds.

Gaps of care in patients with venous thrombotic embolism: a qualitative study.

Abstract: Background Venous thromboembolism (VTE) includes pulmonary embolism (PE) and deep vein thrombosis (DVT), and results in 100,000 deaths annually in the United States. There is low global VTE awareness, including limited data regarding difficulties patients encounter during their management. This study aims to identify a patient's perspective on VTE gaps of care. Methods This is a qualitative study using semi-structured interviews with VTE patients, who had been previously diagnosed and treated for at least one VTE event in their lifetime. Participants were separated in five focused groups; sample size was defined by data saturation. Interviews were audio recorded, transcribed verbatim, and analyzed thematically using framework analysis based on data saturation evaluation. The study was approved by a local institutional review board. We used inductive framework analysis to interpret the data. Results Twenty participants were included in the analysis. Ten participants (50%) were men. Three major themes were identified: 1) concerned about limited disease knowledge; 2) VTE awareness in healthcare system; 3) incomplete communication during transitional and follow-up care. Conclusions Findings suggest that gaps of VTE care extend in different levels of the medical system, including: the patient, physicians, and medical teams. Patients were sensitive to a lack of disease awareness among healthcare providers. There was appreciation for subspecialty care recommended for VTE. In a qualitative study, using the patient perspective, we have detected frustrations and perceived areas of improvement of the care of the patient with VTE. These gaps are anchored in perceived lack of disease awareness and difficult transitional care.

Direct oral factor Xa inhibitors for the treatment of acute cancer-associated venous thromboembolism: A systematic review and network meta-analysis.

Abstract: e23156Background: A direct meta-analysis was performed to explore the efficacy and safety of direct oral factor Xa inhibitors with dalteparin in patients with cancer associated acute venous thrombo...

The Risk of Venous Thromboembolism is Not Equal for all Patients Who Undergo Total Joint Replacement

Abstract: Venous thromboembolism (VTE) is a well-recognized potential complication of several forms of orthopedic surgery. The current guidelines suggest extended use of VTE pharmacological prophylaxis for patients who undergo either total hip arthroplasty (THA) or total knee arthroplasty (TKA). However, the selection of an optimal prophylactic agent, risk stratification, and duration of the at-risk period remain poorly defined. Researchers have tried to adapt multiple assessment tools to bridge this gap. Krauss et al propose the use of the Caprini risk score in the postarthroplasty population. Moreover, Cronin et al complement this publication with concise guidelines for scoring that facilitates the implementation of proper VTE prophylaxis strategies. Ideally, a risk stratification methodology should be easy to implement, be capable to reliably discriminate patients with the highest risk of the development of postoperative VTE, and translate to the VTE risk reduction when used to define the optimal prophylaxis approach. To this end, the Caprini risk score has been extensively validated in surgical patients. In a meta-analysis of 14 776 patients by Pannucci et al, patients with a Caprini risk score > 8 had a significant reduction in thrombosis if they received prophylaxis (odds ratio: 0.41, 95% confidence interval: 0.26-0.65); conversely in patients with a score of less than 6 (75% of the total study population), chemoprophylaxis was not effective. This raises the question as to whether sole use of aspirin for lower risk patients is adequate; indeed the incidence of VTE at 90 days was only 0.64% among the patients randomized to aspirin in a recent randomized controlled trial among patients who underwent THA or TKA. However, all patients (n 1⁄4 3424) in this study received 10 mg of rivaroxaban for the first 5 days and 1.29% developed clinically important bleeding. There was no stratified analysis by VTE risk and risk groups were systematically excluded. In the current edition of The Journal, the idea of personalization of prophylaxis is studied in 1078 patients who underwent THA, THA revision, or TKA. Patients had their VTE risk quantified on the date of surgery. Patients with low risk received 6 weeks of aspirin 325 mg twice daily. The patients with a high risk score and who underwent THA or THA revision received 35 days of prophylactic rivaroxaban or apixaban, whereas those who underwent TKA or TKA revision were prescribed 2 weeks of direct oral anticoagulant followed by aspirin. The authors classified risk using an abbreviated, internally adopted, list of characteristics including: thrombophilia, prior VTE, malignancy, staged surgery, and morbid obesity. Key variables to derive the Caprini score were prospectively collected, which allowed the authors to retrospectively reclassify the entire group with Caprini scores according to the figure in the completion guidelines paper. The performance of the Caprini score in the postarthroplasty population was compared to the department-established guidelines. The key results were

Intermittent pneumatic compression in patients with ESRD. A systematic review

Abstract: Introduction Patients with end-stage renal disease (ESRD) experience frequent hemodialysis (HD) complications. Intradialytic hypotension (IDH) is a common complication presenting in approximately between 20 and 50% of HD sessions. Available interventions such as volume replacement or vasoactive medications are associated with significant side effects. Intermittent pneumatic compression (IPC) has been proposed as a feasible intervention for the prevention of IDH, treatment of peripheral arterial disease and venous ulcers. These devices apply intermittent pressure to the legs improving arterial blood flow, mobilization of pooled blood with an increase in venous return increasing the effective circulatory volume. Our goal was to identify the published clinical evidence on whether IPC has a circulatory benefit and is it well-tolerated among patients receiving HD. Methods We conducted a systematic review to identify studies assessing the efficacy and safety of IPC in patients with ESRD. Our primary outcome was IDH. Secondary outcomes such as HD comfort, ultrafiltration volume, and physical activity were collected. No restrictions where used and we included all observational and interventional studies. Two reviewers performed screening and study quality assessment. Findings We included seven studies. Out of the seven studies, five addressed IDH, and the rest were included for secondary outcomes such as physical capacity and HD comfort. In one randomized crossover trial comparing exercise against IPC, 21 patients were randomized to 3 different arms (no intervention, cycling, IPC) a decrease in the rates of IDH with IPC was described (43%, 38%, and 24% respectively P = 0.014). The smaller studies corroborated these results. All studies where at high risk of bias. Discussion IPC might offer significant benefits for patients undergoing HD not limited to prevention of IDH but also improvement of hemodialysis comfort and physical capacity. However, our results should be interpreted in the context of its limitations.

Rate and impact of venous thromboembolism in patients with ST-segment elevation myocardial infarction: Analysis of the Nationwide Inpatient Sample database 2003-2013.

Abstract: Venous thromboembolism (VTE) and coronary artery disease are major health issues that cause substantial morbidity and mortality. New data have emerged suggesting that these two conditions could have a close relationship. Thus, we sought to determine the trends in annual rate of VTE occurrence in patients with ST-segment elevation myocardial infarction (STEMI) and measure its impact on in-hospital mortality, bleeding complications, and cost and length of hospitalization. We queried the 2003-2013 Nationwide Inpatient Sample databases to identify adults with primary diagnosis of STEMI. VTE events were then allocated. Inpatient outcomes of patients with VTE were compared to those without VTE. Out of 2,495,757 hospitalizations for STEMI, VTE was diagnosed in 25,149 (1%) hospitalizations. Patients who experienced VTE were older (mean age: 67.5 vs 64.8, p < 0.01) and had a higher proportion of black patients (10.1% vs 7.7%, p < 0.001) and females (40.1% vs 35%, p < 0.001) compared to patients without VTE. There was an increasing trend in the rate of VTE during the study period (2003: 0.8% vs 2013: 1.0%, p < 0.001). Patients with VTE had a prolonged hospitalization (median: 9 vs 3 days, p < 0.001), increased cost, higher risk of gastrointestinal bleeding (OR: 2.13, p < 0.001), intracranial hemorrhage (OR: 2.14, p < 0.001), blood transfusions (OR: 1.94, p < 0.001), and mortality (OR: 1.39, p < 0.001). The rate of VTE occurrence in patients with STEMI in our study was 10 per 1000 admissions. VTE was associated with more bleeding complications, longer hospital stays, higher costs, and mortality. These findings suggest that a more aggressive approach for VTE prophylaxis may be warranted in this population.

Postoperative venous thromboembolism and mortality in patients with pancreatic surgery.

Abstract: BACKGROUND AND OBJECTIVES Pancreatic cancer is strongly associated with thrombosis. We investigated early postoperative venous thromboembolism (PVTE) mortality among patients with pancreatic surgery and compared outcomes in adenocarcinoma pancreatic cancer (ACPC) to non-adenocarcinoma pancreatic neoplasm (NACPN). METHODS We analyzed a prospectively collected database of patients who underwent pancreatic cancer or neoplasm-related surgery. As NACPN is underrepresented in other studies, we selected NACPN patients and a random sample of ACPC patients. PVTE was defined as VTE occurring within 3 months of surgical intervention. Statistical analysis was performed using Cox proportional hazards regression. RESULTS A total of 441 pancreatic surgery patients were included, with 331 ACPC and 110 NACPN. Median follow-up was 449 days during which 90 (20.4%) patients developed VTE. PVTE occurred in 53 (12.0%) patients, including 41 (12.4%) ACPC patients and 12 (10.9%) NACPN patients. Those with PVTE had 60% higher mortality rate. A multivariable analysis found that PVTE is an independent predictor of increased mortality (HR Adj, 1.6; 95% CI, 1.1-2.2; P < .01). The mortality impact was not consistent between ACPC (HR, 3.2; 95% CI, 1.3-7.9) and NACPN groups (HR, 1.3; 95% CI, 0.9-1.8). CONCLUSIONS Postoperative venous thromboembolism is an independent predictor of increased mortality in pancreatic surgery, specifically in adenocarcinoma pancreatic cancer surgery.

Pancreatic cancer thromboembolic outcomes: rate of thrombosis after adenocarcinoma and non-adenocarcinoma pancreatic cancer surgery

Abstract: Background The aim of this study was to define the association of non-adenocarcinoma pancreatic cancer (NACPC) as a risk factor for postoperative cancer-associated thrombosis (CAT). Methods We conducted analysis of prospectively collected data of pancreatic cancer surgery. Randomly collected NACPC cases were matched 1:3 to adenocarcinoma cases (ACPC). Variables included comorbidities, demographics, cancer extension, and preoperative Khorana score (KRS). Primary outcome was CAT, which included deep vein thrombosis and pulmonary embolism confirmed by imaging. Categorical variables are presented as percentages, continuous variables as median and range. SPSS, χ2, Cochran-Armitage, and logistic regression were use for analysis. Results The study included 441 patients. Age 65.9±11.5, male 57% (N.=252), 8% (N.=36) had metastasis. IPMN and neuroendocrine were the most common NACPC. Median follow-up was 449 days in which 90 (20%) patients developed CAT. The odds (Odds Ratio [OR] 1.1, 95% Confidence Interval [CI] 0.6- 1.9, P=0.7) and time to venous thromboembolism were not different between NACPC and ACPC. We analyzed for trends of prophylactic strategies by year of surgery; there was no trend for NACPC (P=0.4) or ACPC (P=0.06). KRS was not associated with CAT. In the multivariate analysis, peripheral artery disease (Adjusted Odds Ratio [ORadj] 5.4, 95% CI: 1.7-17.3), ASA class ≥4 (ORadj 3.6; 95% CI: 1.3-10.4), length of stay >9 days (ORadj: 1.9; 1.2-3.2), and cancer vascular invasion (ORadj: 2.9; 95% CI: 1.6-5.3) were associated with CAT. Conclusions The rate of VTE in NACPC after surgery was high and not different than ACPC. Histology type should not govern discrimination in thromboprophylaxis selection or extension.