BACKGROUND Limited data are available on the role of direct oral anticoagulants (DOACs) for the t... more BACKGROUND Limited data are available on the role of direct oral anticoagulants (DOACs) for the treatment of upper extremities deep vein thrombosis (UEDVT). OBJECTIVES The aim of this study was to assess the effectiveness and safety of DOACs in the treatment of UEDVT. METHODS Patients with an objectively confirmed acute UEDVT treated with DOACs were merged from prospective cohorts to a collaborative database. Primary study outcomes were recurrent venous thromboembolism (VTE) and major bleeding occurring during DOAC treatment. RESULTS Overall, 188 patients were included in the study: mean age 52.4 ± 20.4 years, males 43.6%, patients with active cancer 29.2%. Twenty-nine percent of patients had 2 or more risk factors for VTE, 33.0% had catheter-related or pacemaker-related UEDVT. In 13.8% of patients, DOACs were started one month after UEDVT diagnosis or later. Active cancer was an independent predictor for delayed initiation of DOACs (OR 8.1, 95% CI 3.0-22.2). Mean duration of treatment with DOACs was 5.1 ± 2.8 months. During treatment with DOACs, recurrent VTE occurred in 0.9 per 100 patient-year, major bleeding in 1.7 and all-cause deaths in 6.0 per 100 patient-year. No fatal bleeding or fatal VTE recurrence were observed. During 232.1 patient-years of follow-up after DOAC withdrawal, recurrent VTE occurred in 3.0 per 100 patient-year. The 2019 ESC categories for risk of VTE recurrences were able to discriminate patient groups at different risk of events in the on and off-treatment periods. CONCLUSIONS Our data support the feasibility as well as the effectiveness and safety of DOACs for the treatment of acute UEDVT.
BACKGROUND The long-term risk for major bleeding in patients receiving extended (beyond the initi... more BACKGROUND The long-term risk for major bleeding in patients receiving extended (beyond the initial 3 to 6 months) anticoagulant therapy for a first unprovoked venous thromboembolism (VTE) is uncertain. PURPOSE To determine the incidence of major bleeding during extended anticoagulation of up to 5 years among patients with a first unprovoked VTE, overall, and in clinically important subgroups. DATA SOURCES MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials from inception to 23 July 2021. STUDY SELECTION Randomized controlled trials (RCTs) and prospective cohort studies reporting major bleeding among patients with a first unprovoked VTE who were to receive oral anticoagulation for a minimum of 6 additional months after completing at least 3 months of initial anticoagulant treatment. DATA EXTRACTION Two reviewers independently abstracted data and assessed study quality. Unpublished data required for analyses were obtained from authors of included studies. DATA SYNTHESIS Among the 14 RCTs and 13 cohort studies included in the analysis, 9982 patients received a vitamin K antagonist (VKA) and 7220 received a direct oral anticoagulant (DOAC). The incidence of major bleeding per 100 person-years was 1.74 events (95% CI, 1.34 to 2.20 events) with VKAs and 1.12 events (CI, 0.72 to 1.62 events) with DOACs. The 5-year cumulative incidence of major bleeding with VKAs was 6.3% (CI, 3.6% to 10.0%). Among patients receiving either a VKA or a DOAC, the incidence of major bleeding was statistically significantly higher among those who were older than 65 years or had creatinine clearance less than 50 mL/min, a history of bleeding, concomitant use of antiplatelet therapy, or a hemoglobin level less than 100 g/L. The case-fatality rate of major bleeding was 8.3% (CI, 5.1% to 12.2%) with VKAs and 9.7% (CI, 3.2% to 19.2%) with DOACs. LIMITATION Data were insufficient to estimate incidence of major bleeding beyond 1 year of extended anticoagulation with DOACs. CONCLUSION In patients with a first unprovoked VTE, the long-term risks and consequences of anticoagulant-related major bleeding are considerable. This information will help inform patient prognosis and guide decision making about treatment duration for unprovoked VTE. PRIMARY FUNDING SOURCE Canadian Institutes of Health Research. (PROSPERO: CRD42019128597).
European Heart Journal: Acute Cardiovascular Care, 2020
Background: Current strategies for prognostic stratification in haemodynamically stable patients ... more Background: Current strategies for prognostic stratification in haemodynamically stable patients with acute pulmonary embolism require improvement. The aims of this study in haemodynamically stable patients with acute pulmonary embolism were (a) to evaluate the prognostic value of a novel respiratory index (oxygen saturation in air to respiratory rate ratio) and (b) to derive a risk model which includes the respiratory index and evaluate its value in predicting 30-day mortality. Methods: Prospective cohorts of haemodynamically stable patients with acute pulmonary embolism were merged to a collaborative database that served to create two subsequent derivation and validation cohorts based on a temporal criterion. The study outcome was 30-day all-cause death. Results: Thirty-day all-cause death occurred in 7.5% and in 6.9% of patients in the derivation and validation cohorts (each composed of 319 patients). In the derivation cohort, the respiratory index (odds ratio 0.66, 95% confidenc...
Results: HFD rats had obesity and insulin resistance, whereas subsequent orchiectomy did not aggr... more Results: HFD rats had obesity and insulin resistance, whereas subsequent orchiectomy did not aggravate metabolic impairment. Vildagliptin and combined drugs effectively reduced insulin resistance, and TRT and combined drugs restored plasma testosterone levels in HFO, compared with NDS and HFS. LV dysfunction was observed in NDOV, HFS, and HFOV, in which the severity was greatest in HFOV. TRT, vildagliptin, and combined drugs had similar efficacy in increasing LV ejection fraction in both NDO and HFO, compared with sham. Additionally, in NDO and HFO, all pharmacological interventions attenuated mitochondrial oxidative stress, reduced mitochondrial membrane depolarization and mitochondrial swelling, and increased mitochondrial respiration, compared with sham. Furthermore, cardiac apoptosis was decreased in all treatment groups. However, there were no synergistic effects of combined low-dose TRT and vildagliptin on LV function, mitochondrial function, and apoptosis in NDO and HFO (Figure). Figure 1 Conclusion: Combined low-dose TRT with vildagliptin and TRT shared similar efficacy in improving LV function via reducing mitochondrial dysfunction and apoptosis in obese-insulin resistant rats with testosterone deprivation. Therefore, this combined drug could be considered as an alternative intervention for those who have cardiovascular risk from testosterone therapy.
Introduction The interaction between sex and specific provoking risk factors for venous thromboem... more Introduction The interaction between sex and specific provoking risk factors for venous thromboembolism (VTE) may influence initial presentation and prognosis. Purpose We investigated the impact of sex on the risk of recurrence across subgroups of patients with first VTE classified according to baseline risk factors. Methods PREFER in VTE was an international, non-interventional registry (2013–2015) including patients with a first episode of acute symptomatic objectively diagnosed VTE. We studied the risk of recurrence in patients classified according to baseline provoking risk factors for VTE consisted of i) major transient (major surgery/trauma, >5 days in bed), ii) minor transient (pregnancy or puerperium, estroprogestinic therapy, prolonged immobilization, current infection or bone fracture/soft tissue trauma); iii) unprovoked events, iv) active cancer-associated VTE. Results A total of 3,455 patients diagnosed with first acute VTE were identified, of whom 1,623 (47%) were wo...
The data presented in this article are related to the research article entitled "Patients aged 90... more The data presented in this article are related to the research article entitled "Patients aged 90 years or older with atrial fibrillation treated with oral anticoagulants: A multicentre observational study" [1]. This article unveils original data of a cohort of 546 patients aged 90 years or older with non-valvular atrial fibrillation treated with oral anticoagulants. Here, we describe the time course of ischemic stroke and systemic embolism and of major bleeding according to the presence of outcome predictors and report the causes of permanent discontinuation and of death. Furthermore, we report data on the incidence of ischemic stroke and systemic embolism, of major bleeding, of permanent discontinuation and of all-cause death comparing i) oral anticoagulant naïve users vs. long-term oral anticoagulant users, ii) patients on anticoagulant therapy for less than 2 years (new users) vs. patients on anticoagulant therapy for more than 2 years. The material of this data article provides a better understanding on the use of oral anticoagulants in this fragile population and facilitates further critical analysis. Moreover, it aims at highlighting the importance of increasing knowledge in patients aged 90 years or older. These
Background: Limited data are available on the use of direct oral anticoagulants (DOACs) in patien... more Background: Limited data are available on the use of direct oral anticoagulants (DOACs) in patients with cancer and atrial fibrillation (AF). Methods: Consecutive patients with non-valvular AF treated with DOACs were enrolled in a prospective cohort with the aim of evaluating thromboembolic (ischemic stroke or transient ischemic attack or systemic embolism) and major bleeding (MB) events according to presence and type of cancer. The risk of study outcomes over time was compared using Kaplan-Meier method and log-rank test or Cox proportional hazards regression. Results: 2304 patients with non-valvular AF receiving DOACs were enrolled and 16 excluded: 2288 analysed of whom 289 (12.6%) had cancer. Gastrointestinal (21%), genitourinary (15%), prostate (15%), haematological (14%), breast (13%), and lung (8%) were the more frequent sites of cancer. After a mean follow-up of 451 days, thromboembolic events occurred in 2.1% and 0.8% patient-year of cancer and non-cancer patients (adjusted-HR 2.58, 95% CI 1.08-6.16, p = 0.033). The rate of MB was 6.6% and 3.0% patientyear in cancer and non-cancer patients (adjusted-HR 2.02, 95% CI 1.25-3.27, p = 0.004). The differences in bleeding were mainly accounted for by bleeding at gastrointestinal and genitourinary sites. No significant differences were found concerning the rates of non-cancer-related mortality, fatal bleeding or fatal thrombotic events. Conclusions: In this study, the higher bleeding risk found in cancer compared to non-cancer patients was mainly due to an excess of bleeding at gastrointestinal and at genitourinary sites. Larger studies on the optimal management of cancer patients with AF are needed.
Background: Persistence to treatment affects clinical outcomes in patients with chronic disease s... more Background: Persistence to treatment affects clinical outcomes in patients with chronic disease such as atrial fibrillation (AF). Methods: This prospective cohort study included consecutive non-valvular AF patients prescribed with non-vitamin K oral anticoagulants (NOACs) and investigated for any permanent discontinuation at 1-year of this therapy, as well as any reasons for discontinuation. Results: Overall, 1305 patients were prescribed with dabigatran (N = 473), rivaroxaban (N = 425) or apixaban (N = 407). Of these, 201 patients (15.4%) discontinued NOACs during the first year of treatment. More than 60% of these discontinuations occurred during the first 6 months. Reasons for discontinuation included: dyspepsia or abdominal pain in 38 patients (2.9%) and bleeding in 59 (4.5%). Discontinuation for the former occurred earlier (50% within 2 months) compared to the latter (66% after the first 4 months). The prescription of reduced NOAC doses resulted being an independent predictor of discontinuation (OR 1.74, 95% CI 1.23-2.45, p = 0.002). Regarding the use of dabigatran, rivaroxaban and apixaban, the following were observed: discontinuers were 22.0% (95% CI 18.5-25.9), 14.4% (95% CI 11.3-18.0) and 8.8% (95% CI 6.5-12.0), the risk of discontinuation associated with bleeding was 20.2%, 44.3% and 30.6% and dyspepsia or abdominal pain was 35.6%, 1.6% and 0%, respectively. Conclusion: Discontinuation of NOACs in AF patients was relatively common and more than often occurred in the first six months after prescription. Patients treated with reduced doses of NOACs had a higher probability to discontinue compared to those who were prescribed conventional doses.
Giornale italiano di cardiologia (2006), Sep 1, 2016
The new oral anticoagulants (NOACs) have radically changed the approach to the treatment and prev... more The new oral anticoagulants (NOACs) have radically changed the approach to the treatment and prevention of thromboembolic pulmonary embolism. The authors of this position paper face, in succession, issues concerning NOACs, including 1) their mechanism of action, pharmacodynamics and pharmacokinetics; 2) the use in the acute phase with the "double drug single dose" approach or with "single drug double dose"; 3) the use in the extended phase with demonstrated efficacy and with low incidence of bleeding events; 4) the encouraging use of NOACs in particular subgroups of patients such as those with cancer, the ones under- or overweight, with renal insufficiency (creatinine clearance >30 ml/min), the elderly (>75 years); 5) they propose a possible laboratory clinical pathway for follow-up; 6) carry out an examination on the main drug interactions, their potential bleeding risk, and the way to deal with some bleeding complications. The authors conclude that the us...
BACKGROUND Current guidelines recommend vitamin K antagonists (VKAs) or non-vitamin K antagonist ... more BACKGROUND Current guidelines recommend vitamin K antagonists (VKAs) or non-vitamin K antagonist oral anticoagulants (NOACs) for stroke prevention in patients with non-valvular atrial fibrillation (AF). METHODS We compared the clinical features of consecutive in- and out-patients with non-valvular AF newly-treated with NOACs or on treatment with VKAs. RESULTS Overall, 1314 patients newly-treated with NOACs and 1024 on treatment with VKAs were included in the study. The mean CHA2DS2-VASc score was 4.3±1.5 and 4.0±1.5 and the mean HAS-BLED score was 2.8±1.2 and 2.2±1.1 in the two groups, respectively (both p<0.001). Hypertension, previous stroke, female gender, vascular diseases and previous bleeding were more prevalent in NOACs patients. Renal failure, age ≥75years and congestive heart failure were more prevalent in VKAs patients. Among NOACs patients, 438 were given dabigatran, 463 rivaroxaban and 413 apixaban (33%, 35% and 31%, respectively). The mean CHA2DS2-VASc and HAS-BLED scores were higher in rivaroxaban or apixaban patients compared with dabigatran (both p<0.001) and VKAs patients (both p<0.001). A lower mean age was observed in patients newly-treated with dabigatran. Patients newly-treated with reduced doses of NOACs (599 patients, 45.5%) had a higher CHA2DS2-VASc (4.8±1.4 vs. 3.9±1.5 vs. 4.0±1.5) and HAS-BLED (2.9±1.1 vs. 2.8±1.2 vs. 2.2±1.1) scores compared with those treated with regular doses of NOACs or VKAs. CONCLUSION Patients given rivaroxaban and apixaban in clinical practice have a higher thrombotic and hemorrhagic risk in comparison with patients given dabigatran or VKAs. A considerable proportion of patients receive reduced doses of NOACs.
The efficacy and safety of primary prophylaxis in advanced pancreatic cancer (APC) has been demon... more The efficacy and safety of primary prophylaxis in advanced pancreatic cancer (APC) has been demonstrated in randomized controlled studies. Current guidelines suggest use of primary prophylaxis in high risk ambulatory cancer patients. The VTE in cancer working group in our centre reviewed our experience with FRAGEM and relevant literature. Observations: (1) Dose: (a) conventional prophylactic dosing is not established in APC (b) 200IU/kg followed by 150IU/kg dalteparin may be superior to 1mg/kg followed by 40mg enoxaparin. (2) Duration of treatment: (a) FRAGEM observed a rapid increase in VTE events after the 3-month treatment period. Transfer to 40mg enoxaparin in CONKO-04 after 3 months also demonstrated reduced efficacy. (3) Recognition that bleeding in metastatic incurable pancreatic cancer is not uncommon even without anticoagulation. Cumulative incidence rates of major bleeding over the first 3 months were: 4.5% vs. 3.4% (NS) in CONKO-04 and 3.4% vs. 3.1 % (NS) in FRAGEM (treatment vs observation arms respectively). aim: This abstract describes our interpretation and experience on implementing available evidence for primary prophylaxis in ambulatory APC patients. materials and methods: A simplified body weight-adjusted schedule for thromboprophylaxis with Dalteparin for the ambulant APC patient was agreed as follows: <50kg: 7500 IU, 50-80kg: 10,000 IU, >80kg: 12,500 IU. Eligible patients: All patients with advanced / metastatic pancreatic cancer undergoing palliative chemotherapy. Dalteparin treatment was initiated at least one day prior to the first administration of chemotherapy and continued until death or unacceptable toxicity (bleeding). This guideline was implemented in May 2009. A departmental audit was conducted for patients treated till December 2012 to assess efficacy and safety. results: Results of the audit have been presented in an analysis including 67 patients. The compound adverse outcome (CAE) in this cohort was 24% (VTE: 13%, bleeding: 11%). For patients with no prior exposure to anticoagulation CAE rate was 18% (VTE: 7%, bleeding: 11%) with a median duration of LMWH treatment of 8 months. The majority of the bleeding events observed were due to cancer related lesions (duodenal infiltration or varices). VTE and bleeding rates were similar to published experience with extended duration therapeutic LMWH in cancer-related VTE. VTE risk appeared improved compared to the 3-month regimen of FRAGEM. Conclusions: In our opinion, thromboprophylaxis in ambulatory APC is a pragmatic evidence-based approach trying to deal with a serious cancer related complication that affects these patients. It is expected that data from further randomised trials (e.g SELECT-D and CASSINI) will provide further evidence in this area.
The European Society of Cardiology (ESC) has proposed an updated risk stratification model for de... more The European Society of Cardiology (ESC) has proposed an updated risk stratification model for death in patients with acute pulmonary embolism based on clinical scores (Pulmonary Embolism Severity Index (PESI) or simplified PESI (sPESI)), right ventricle dysfunction (RVD) and elevated serum troponin (2014 ESC model).We assessed the ability of the 2014 ESC model to predict 30-day death after acute pulmonary embolism. Consecutive patients with symptomatic, confirmed pulmonary embolism included in prospective cohorts were merged in a collaborative database. Patients’ risk was classified as high (shock or hypotension), intermediate-high (RVD and elevated troponin), intermediate-low (RVD or increased troponin or none) and low (sPESI 0). Study outcomes were death and pulmonary embolism-related death at 30 days.Among 906 patients (mean±sd age 68±16, 489 females), death and pulmonary embolism-related death occurred in 7.2% and 4.1%, respectively. Death rate was 22% in “high-risk” (95% CI 14...
We examined the impact of sentinel lymph node (SLN) biopsy among patients with primary melanoma t... more We examined the impact of sentinel lymph node (SLN) biopsy among patients with primary melanoma that exceeded 4.0 mm in Breslow thickness, treated in our Institution from 1998 until 2009. According to Kaplan-Meier statistics, overall survival (OS) and disease-free survival (DFS) were assessed in patients with: i) disseminated disease at diagnosis with respect to patients undergoing SLN biopsy and ii) positive SLN and negative SLN. The effect of age, thickness and number of positive SLN on survival was also calculated. Forty-three patients with thick melanoma were included (29 men and 14 women; mean age 65 ± 17 years, tumor thickness ranging from 4 to 20 mm). Thirteen patients (30%) were not eligible for SLN biopsy due to metastatic disease or poor clinical condition. Biopsy was performed on 30 patients: 14 with positive SLN (46.7%, group A) and 16 with negative SLN (53.3%, group B). Seven patients (50%) died in group A and 2 patients (13%) in group B (mean follow-up 28 and 59 months...
Combined antiplatelet and anticoagulant therapy has been suggested for those clinical conditions ... more Combined antiplatelet and anticoagulant therapy has been suggested for those clinical conditions in which conventional antithrombotic regimens have shown suboptimal efficacy, and in patients with indication for both: antiplatelet and anticoagulant therapy. Clinical trials aimed at assessing the clinical benefit of the association with respect to mono-therapy have been conducted in patients with atrial fibrillation, in patients with recent myocardial infarction, and in patients with prosthetic heart valves. Overall, a favorable benefit-risk profile of combined therapy in comparison to anticoagulant alone has been observed in patients with mechanical prosthetic heart valves and in those with coronary artery disease while no clear advantage has been shown in patients with atrial fibrillation. In almost all these studies, however, a higher risk of major bleeding has been observed in patients receiving combined therapy in comparison to patients receiving warfarin alone. Thus, a combined regimen of anticoagulant and antiplatelet therapy should be reserved for selected patients at high risk of thromboembolic events who have a low risk of bleeding.
Introduction: Direct oral anticoagulants (DOACs) are increasingly used for anticoagulation or pre... more Introduction: Direct oral anticoagulants (DOACs) are increasingly used for anticoagulation or prevention of thromboembolic events in conditions that may co-occur with pregnancy. However, evidence regarding efficacy and safety during pregnancy is scarce. Aim: To review the current literature concerning the efficacy, safety and outcome of DOACs during pregnancy in humans. Methods: We systematically searched the MedLine public database for all studies describing the use of DOACs during pregnancy published up to July 4th 2017. Results: 236 cases of DOAC use during pregnancy were reported. Rivaroxaban was the most reported DOAC (n = 178). DOACs were mostly used for prophylaxis or treatment of venous thromboembolism (n = 91). DOACs were discontinued within the first 2 months of pregnancy in 84%, maximum reported duration of use was 26 weeks. Pregnancy outcome data were available for 140 pregnancies. Thirty-nine pregnancies were electively terminated. In the remaining 101 pregnancies total miscarriage rate was 31% (n = 31) and live birth rate was 68% (n = 69, 1 missing). Foetal and neonatal abnormalities were reported in 8 pregnancies, of which at least half were suspected to be related to rivaroxaban use during the 1st trimester of pregnancy. In only 18% of cases (n = 42), the presence or absence of thrombotic and bleeding complications was reported. Conclusion: The limited available evidence raises concern regarding embryo-foetal safety, with high incidence of miscarriages and a 4% rate of anomalies with the use of rivaroxaban. Not enough data are available to judge safety and efficacy of the use of DOACs during pregnancy.
BACKGROUND: Direct oral anticoagulants (DOAs) have been shown to be as eff ective and at least as... more BACKGROUND: Direct oral anticoagulants (DOAs) have been shown to be as eff ective and at least as safe as conventional anticoagulation for the prevention of recurrences in patients with VTE. Whether this is the case in patients with cancer-associated VTE remains undefi ned. METHODS: We performed a meta-analysis of randomized controlled trials with the aim of assessing the effi cacy and safety of DOAs in patients with VTE and cancer. MEDLINE, EMBASE, and CENTRAL were searched up to December 2013 with no language restriction. Th e primary outcome of the analysis was recurrent VTE. Data on major bleeding (MB) and clinically relevant nonmajor bleeding were analyzed. Data were pooled and compared by ORs and 95% CIs. RESULTS: Overall, 10 studies comparing DOAs with conventional anticoagulation for treatment of VTE including patients with cancer were included in the review. Six studies were included in the meta-analysis (two with dabigatran, two with rivaroxaban, one with edoxaban, and one with apixaban), accounting for a total of 1,132 patients. VTE recurred in 23 of 595 (3.9%) and in 32 of 537 (6.0%) patients with cancer treated with DOAs and conventional treatment, respectively (OR, 0.63; 95% CI, 0.37-1.10; I 2 , 0%). MB occurred in 3.2% and 4.2% of patients receiving DOAs and conventional treatment, respectively (OR, 0.77; 95% CI, 0.41-1.44; I 2 , 0%). CONCLUSIONS: DOAs seem to be as eff ective and safe as conventional treatment for the prevention of VTE in patients with cancer. Further clinical trials in patients with cancer-associated VTE should be performed to confi rm these results.
Journal of Hepato-Biliary-Pancreatic Sciences, 2014
Laparoscopic cholecystectomy (LC) has largely replaced conventional cholecystectomy in the past d... more Laparoscopic cholecystectomy (LC) has largely replaced conventional cholecystectomy in the past decade. However, there are still limited data about the value of prophylactic sub-hepatic drainage for elective uncomplicated LC. We carried out a systematic review of the literature in order to perform a meta-analysis about this issue. An unrestricted search in MEDLINE, EMBASE and Cochrane Library up to 31 December 2013 was performed. Overall, seven high-methodological quality randomized controlled trials (RCTs) were included in the meta-analysis, resulting in 1310 patients totally. The incidence of abdominal collections, wound infection and overall mortality according to the presence or absence of the sub-hepatic drainage were meta-analyzed. Sub-hepatic drainage showed an increase in the abdominal collection rate in patients who underwent elective uncomplicated LC (OR 1.56, 95% CI 1.00-2.43) if compared to patients without drainage. A non-significant correlation was found in overall mortality and infection rates. The meta-analysis shows that the presence of the sub-hepatic drainage does not reduce the incidence of abdominal collection after uncomplicated LC, whereas it does not influence wound infection and mortality rates, postoperative pain and hospital stay.
Heparin, fondaparinux and vitamin K antagonists (VKAs) are effective for the prevention and treat... more Heparin, fondaparinux and vitamin K antagonists (VKAs) are effective for the prevention and treatment of venous thromboembolism. VKAs reduce by almost 60% the rate of cardioembolic complications in patients with atrial fibrillation. The risk for bleeding and the inconvenience for laboratory monitoring, dose adjustment and drug or food interactions are the main limits for VKAs while parenteral administration is the main limit for heparin and fondaparinux. New oral anticoagulants with more predictable anticoagulant response and no need for laboratory monitoring have been shown to be effective for the prevention and treatment of venous thromboembolism and for the prevention of stroke and systemic embolism in patients with atrial fibrillation. The pharmacokinetic and pharmacodynamic profile of the new agents differ for mechanisms of actionmainly anti Xa and one antithrombin agent-bioavailability, half life, renal or live clearance. Drug interactions have been described with the new agents and inhibitors or inducers of P-gp or CYP3A4. Overall, in the prevention of venous thromboembolism after major elective orthopaedic surgery dabigatran was shown to be non-inferior, rivaroxaban and apixaban to be superior to enoxaparin. Both, rivaroxaban and dabigatran were shown to be non-inferior to low-molecular weight heparin and VKAs for the treatment of venous thromboembolism. Dabigatran 150 mg twice daily reduced the incidence of both ischemic and hemorrhagic stroke in patients with atrial fibrillation respect to warfarin. In these patients rivaroxaban and apixaban reduced the incidence of hemorrhagic stroke with a similar incidence of ischemic stroke. No bleeding concern emerged with the new anticoagulant agents in this indication.
BACKGROUND Limited data are available on the role of direct oral anticoagulants (DOACs) for the t... more BACKGROUND Limited data are available on the role of direct oral anticoagulants (DOACs) for the treatment of upper extremities deep vein thrombosis (UEDVT). OBJECTIVES The aim of this study was to assess the effectiveness and safety of DOACs in the treatment of UEDVT. METHODS Patients with an objectively confirmed acute UEDVT treated with DOACs were merged from prospective cohorts to a collaborative database. Primary study outcomes were recurrent venous thromboembolism (VTE) and major bleeding occurring during DOAC treatment. RESULTS Overall, 188 patients were included in the study: mean age 52.4 ± 20.4 years, males 43.6%, patients with active cancer 29.2%. Twenty-nine percent of patients had 2 or more risk factors for VTE, 33.0% had catheter-related or pacemaker-related UEDVT. In 13.8% of patients, DOACs were started one month after UEDVT diagnosis or later. Active cancer was an independent predictor for delayed initiation of DOACs (OR 8.1, 95% CI 3.0-22.2). Mean duration of treatment with DOACs was 5.1 ± 2.8 months. During treatment with DOACs, recurrent VTE occurred in 0.9 per 100 patient-year, major bleeding in 1.7 and all-cause deaths in 6.0 per 100 patient-year. No fatal bleeding or fatal VTE recurrence were observed. During 232.1 patient-years of follow-up after DOAC withdrawal, recurrent VTE occurred in 3.0 per 100 patient-year. The 2019 ESC categories for risk of VTE recurrences were able to discriminate patient groups at different risk of events in the on and off-treatment periods. CONCLUSIONS Our data support the feasibility as well as the effectiveness and safety of DOACs for the treatment of acute UEDVT.
BACKGROUND The long-term risk for major bleeding in patients receiving extended (beyond the initi... more BACKGROUND The long-term risk for major bleeding in patients receiving extended (beyond the initial 3 to 6 months) anticoagulant therapy for a first unprovoked venous thromboembolism (VTE) is uncertain. PURPOSE To determine the incidence of major bleeding during extended anticoagulation of up to 5 years among patients with a first unprovoked VTE, overall, and in clinically important subgroups. DATA SOURCES MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials from inception to 23 July 2021. STUDY SELECTION Randomized controlled trials (RCTs) and prospective cohort studies reporting major bleeding among patients with a first unprovoked VTE who were to receive oral anticoagulation for a minimum of 6 additional months after completing at least 3 months of initial anticoagulant treatment. DATA EXTRACTION Two reviewers independently abstracted data and assessed study quality. Unpublished data required for analyses were obtained from authors of included studies. DATA SYNTHESIS Among the 14 RCTs and 13 cohort studies included in the analysis, 9982 patients received a vitamin K antagonist (VKA) and 7220 received a direct oral anticoagulant (DOAC). The incidence of major bleeding per 100 person-years was 1.74 events (95% CI, 1.34 to 2.20 events) with VKAs and 1.12 events (CI, 0.72 to 1.62 events) with DOACs. The 5-year cumulative incidence of major bleeding with VKAs was 6.3% (CI, 3.6% to 10.0%). Among patients receiving either a VKA or a DOAC, the incidence of major bleeding was statistically significantly higher among those who were older than 65 years or had creatinine clearance less than 50 mL/min, a history of bleeding, concomitant use of antiplatelet therapy, or a hemoglobin level less than 100 g/L. The case-fatality rate of major bleeding was 8.3% (CI, 5.1% to 12.2%) with VKAs and 9.7% (CI, 3.2% to 19.2%) with DOACs. LIMITATION Data were insufficient to estimate incidence of major bleeding beyond 1 year of extended anticoagulation with DOACs. CONCLUSION In patients with a first unprovoked VTE, the long-term risks and consequences of anticoagulant-related major bleeding are considerable. This information will help inform patient prognosis and guide decision making about treatment duration for unprovoked VTE. PRIMARY FUNDING SOURCE Canadian Institutes of Health Research. (PROSPERO: CRD42019128597).
European Heart Journal: Acute Cardiovascular Care, 2020
Background: Current strategies for prognostic stratification in haemodynamically stable patients ... more Background: Current strategies for prognostic stratification in haemodynamically stable patients with acute pulmonary embolism require improvement. The aims of this study in haemodynamically stable patients with acute pulmonary embolism were (a) to evaluate the prognostic value of a novel respiratory index (oxygen saturation in air to respiratory rate ratio) and (b) to derive a risk model which includes the respiratory index and evaluate its value in predicting 30-day mortality. Methods: Prospective cohorts of haemodynamically stable patients with acute pulmonary embolism were merged to a collaborative database that served to create two subsequent derivation and validation cohorts based on a temporal criterion. The study outcome was 30-day all-cause death. Results: Thirty-day all-cause death occurred in 7.5% and in 6.9% of patients in the derivation and validation cohorts (each composed of 319 patients). In the derivation cohort, the respiratory index (odds ratio 0.66, 95% confidenc...
Results: HFD rats had obesity and insulin resistance, whereas subsequent orchiectomy did not aggr... more Results: HFD rats had obesity and insulin resistance, whereas subsequent orchiectomy did not aggravate metabolic impairment. Vildagliptin and combined drugs effectively reduced insulin resistance, and TRT and combined drugs restored plasma testosterone levels in HFO, compared with NDS and HFS. LV dysfunction was observed in NDOV, HFS, and HFOV, in which the severity was greatest in HFOV. TRT, vildagliptin, and combined drugs had similar efficacy in increasing LV ejection fraction in both NDO and HFO, compared with sham. Additionally, in NDO and HFO, all pharmacological interventions attenuated mitochondrial oxidative stress, reduced mitochondrial membrane depolarization and mitochondrial swelling, and increased mitochondrial respiration, compared with sham. Furthermore, cardiac apoptosis was decreased in all treatment groups. However, there were no synergistic effects of combined low-dose TRT and vildagliptin on LV function, mitochondrial function, and apoptosis in NDO and HFO (Figure). Figure 1 Conclusion: Combined low-dose TRT with vildagliptin and TRT shared similar efficacy in improving LV function via reducing mitochondrial dysfunction and apoptosis in obese-insulin resistant rats with testosterone deprivation. Therefore, this combined drug could be considered as an alternative intervention for those who have cardiovascular risk from testosterone therapy.
Introduction The interaction between sex and specific provoking risk factors for venous thromboem... more Introduction The interaction between sex and specific provoking risk factors for venous thromboembolism (VTE) may influence initial presentation and prognosis. Purpose We investigated the impact of sex on the risk of recurrence across subgroups of patients with first VTE classified according to baseline risk factors. Methods PREFER in VTE was an international, non-interventional registry (2013–2015) including patients with a first episode of acute symptomatic objectively diagnosed VTE. We studied the risk of recurrence in patients classified according to baseline provoking risk factors for VTE consisted of i) major transient (major surgery/trauma, >5 days in bed), ii) minor transient (pregnancy or puerperium, estroprogestinic therapy, prolonged immobilization, current infection or bone fracture/soft tissue trauma); iii) unprovoked events, iv) active cancer-associated VTE. Results A total of 3,455 patients diagnosed with first acute VTE were identified, of whom 1,623 (47%) were wo...
The data presented in this article are related to the research article entitled "Patients aged 90... more The data presented in this article are related to the research article entitled "Patients aged 90 years or older with atrial fibrillation treated with oral anticoagulants: A multicentre observational study" [1]. This article unveils original data of a cohort of 546 patients aged 90 years or older with non-valvular atrial fibrillation treated with oral anticoagulants. Here, we describe the time course of ischemic stroke and systemic embolism and of major bleeding according to the presence of outcome predictors and report the causes of permanent discontinuation and of death. Furthermore, we report data on the incidence of ischemic stroke and systemic embolism, of major bleeding, of permanent discontinuation and of all-cause death comparing i) oral anticoagulant naïve users vs. long-term oral anticoagulant users, ii) patients on anticoagulant therapy for less than 2 years (new users) vs. patients on anticoagulant therapy for more than 2 years. The material of this data article provides a better understanding on the use of oral anticoagulants in this fragile population and facilitates further critical analysis. Moreover, it aims at highlighting the importance of increasing knowledge in patients aged 90 years or older. These
Background: Limited data are available on the use of direct oral anticoagulants (DOACs) in patien... more Background: Limited data are available on the use of direct oral anticoagulants (DOACs) in patients with cancer and atrial fibrillation (AF). Methods: Consecutive patients with non-valvular AF treated with DOACs were enrolled in a prospective cohort with the aim of evaluating thromboembolic (ischemic stroke or transient ischemic attack or systemic embolism) and major bleeding (MB) events according to presence and type of cancer. The risk of study outcomes over time was compared using Kaplan-Meier method and log-rank test or Cox proportional hazards regression. Results: 2304 patients with non-valvular AF receiving DOACs were enrolled and 16 excluded: 2288 analysed of whom 289 (12.6%) had cancer. Gastrointestinal (21%), genitourinary (15%), prostate (15%), haematological (14%), breast (13%), and lung (8%) were the more frequent sites of cancer. After a mean follow-up of 451 days, thromboembolic events occurred in 2.1% and 0.8% patient-year of cancer and non-cancer patients (adjusted-HR 2.58, 95% CI 1.08-6.16, p = 0.033). The rate of MB was 6.6% and 3.0% patientyear in cancer and non-cancer patients (adjusted-HR 2.02, 95% CI 1.25-3.27, p = 0.004). The differences in bleeding were mainly accounted for by bleeding at gastrointestinal and genitourinary sites. No significant differences were found concerning the rates of non-cancer-related mortality, fatal bleeding or fatal thrombotic events. Conclusions: In this study, the higher bleeding risk found in cancer compared to non-cancer patients was mainly due to an excess of bleeding at gastrointestinal and at genitourinary sites. Larger studies on the optimal management of cancer patients with AF are needed.
Background: Persistence to treatment affects clinical outcomes in patients with chronic disease s... more Background: Persistence to treatment affects clinical outcomes in patients with chronic disease such as atrial fibrillation (AF). Methods: This prospective cohort study included consecutive non-valvular AF patients prescribed with non-vitamin K oral anticoagulants (NOACs) and investigated for any permanent discontinuation at 1-year of this therapy, as well as any reasons for discontinuation. Results: Overall, 1305 patients were prescribed with dabigatran (N = 473), rivaroxaban (N = 425) or apixaban (N = 407). Of these, 201 patients (15.4%) discontinued NOACs during the first year of treatment. More than 60% of these discontinuations occurred during the first 6 months. Reasons for discontinuation included: dyspepsia or abdominal pain in 38 patients (2.9%) and bleeding in 59 (4.5%). Discontinuation for the former occurred earlier (50% within 2 months) compared to the latter (66% after the first 4 months). The prescription of reduced NOAC doses resulted being an independent predictor of discontinuation (OR 1.74, 95% CI 1.23-2.45, p = 0.002). Regarding the use of dabigatran, rivaroxaban and apixaban, the following were observed: discontinuers were 22.0% (95% CI 18.5-25.9), 14.4% (95% CI 11.3-18.0) and 8.8% (95% CI 6.5-12.0), the risk of discontinuation associated with bleeding was 20.2%, 44.3% and 30.6% and dyspepsia or abdominal pain was 35.6%, 1.6% and 0%, respectively. Conclusion: Discontinuation of NOACs in AF patients was relatively common and more than often occurred in the first six months after prescription. Patients treated with reduced doses of NOACs had a higher probability to discontinue compared to those who were prescribed conventional doses.
Giornale italiano di cardiologia (2006), Sep 1, 2016
The new oral anticoagulants (NOACs) have radically changed the approach to the treatment and prev... more The new oral anticoagulants (NOACs) have radically changed the approach to the treatment and prevention of thromboembolic pulmonary embolism. The authors of this position paper face, in succession, issues concerning NOACs, including 1) their mechanism of action, pharmacodynamics and pharmacokinetics; 2) the use in the acute phase with the "double drug single dose" approach or with "single drug double dose"; 3) the use in the extended phase with demonstrated efficacy and with low incidence of bleeding events; 4) the encouraging use of NOACs in particular subgroups of patients such as those with cancer, the ones under- or overweight, with renal insufficiency (creatinine clearance >30 ml/min), the elderly (>75 years); 5) they propose a possible laboratory clinical pathway for follow-up; 6) carry out an examination on the main drug interactions, their potential bleeding risk, and the way to deal with some bleeding complications. The authors conclude that the us...
BACKGROUND Current guidelines recommend vitamin K antagonists (VKAs) or non-vitamin K antagonist ... more BACKGROUND Current guidelines recommend vitamin K antagonists (VKAs) or non-vitamin K antagonist oral anticoagulants (NOACs) for stroke prevention in patients with non-valvular atrial fibrillation (AF). METHODS We compared the clinical features of consecutive in- and out-patients with non-valvular AF newly-treated with NOACs or on treatment with VKAs. RESULTS Overall, 1314 patients newly-treated with NOACs and 1024 on treatment with VKAs were included in the study. The mean CHA2DS2-VASc score was 4.3±1.5 and 4.0±1.5 and the mean HAS-BLED score was 2.8±1.2 and 2.2±1.1 in the two groups, respectively (both p<0.001). Hypertension, previous stroke, female gender, vascular diseases and previous bleeding were more prevalent in NOACs patients. Renal failure, age ≥75years and congestive heart failure were more prevalent in VKAs patients. Among NOACs patients, 438 were given dabigatran, 463 rivaroxaban and 413 apixaban (33%, 35% and 31%, respectively). The mean CHA2DS2-VASc and HAS-BLED scores were higher in rivaroxaban or apixaban patients compared with dabigatran (both p<0.001) and VKAs patients (both p<0.001). A lower mean age was observed in patients newly-treated with dabigatran. Patients newly-treated with reduced doses of NOACs (599 patients, 45.5%) had a higher CHA2DS2-VASc (4.8±1.4 vs. 3.9±1.5 vs. 4.0±1.5) and HAS-BLED (2.9±1.1 vs. 2.8±1.2 vs. 2.2±1.1) scores compared with those treated with regular doses of NOACs or VKAs. CONCLUSION Patients given rivaroxaban and apixaban in clinical practice have a higher thrombotic and hemorrhagic risk in comparison with patients given dabigatran or VKAs. A considerable proportion of patients receive reduced doses of NOACs.
The efficacy and safety of primary prophylaxis in advanced pancreatic cancer (APC) has been demon... more The efficacy and safety of primary prophylaxis in advanced pancreatic cancer (APC) has been demonstrated in randomized controlled studies. Current guidelines suggest use of primary prophylaxis in high risk ambulatory cancer patients. The VTE in cancer working group in our centre reviewed our experience with FRAGEM and relevant literature. Observations: (1) Dose: (a) conventional prophylactic dosing is not established in APC (b) 200IU/kg followed by 150IU/kg dalteparin may be superior to 1mg/kg followed by 40mg enoxaparin. (2) Duration of treatment: (a) FRAGEM observed a rapid increase in VTE events after the 3-month treatment period. Transfer to 40mg enoxaparin in CONKO-04 after 3 months also demonstrated reduced efficacy. (3) Recognition that bleeding in metastatic incurable pancreatic cancer is not uncommon even without anticoagulation. Cumulative incidence rates of major bleeding over the first 3 months were: 4.5% vs. 3.4% (NS) in CONKO-04 and 3.4% vs. 3.1 % (NS) in FRAGEM (treatment vs observation arms respectively). aim: This abstract describes our interpretation and experience on implementing available evidence for primary prophylaxis in ambulatory APC patients. materials and methods: A simplified body weight-adjusted schedule for thromboprophylaxis with Dalteparin for the ambulant APC patient was agreed as follows: <50kg: 7500 IU, 50-80kg: 10,000 IU, >80kg: 12,500 IU. Eligible patients: All patients with advanced / metastatic pancreatic cancer undergoing palliative chemotherapy. Dalteparin treatment was initiated at least one day prior to the first administration of chemotherapy and continued until death or unacceptable toxicity (bleeding). This guideline was implemented in May 2009. A departmental audit was conducted for patients treated till December 2012 to assess efficacy and safety. results: Results of the audit have been presented in an analysis including 67 patients. The compound adverse outcome (CAE) in this cohort was 24% (VTE: 13%, bleeding: 11%). For patients with no prior exposure to anticoagulation CAE rate was 18% (VTE: 7%, bleeding: 11%) with a median duration of LMWH treatment of 8 months. The majority of the bleeding events observed were due to cancer related lesions (duodenal infiltration or varices). VTE and bleeding rates were similar to published experience with extended duration therapeutic LMWH in cancer-related VTE. VTE risk appeared improved compared to the 3-month regimen of FRAGEM. Conclusions: In our opinion, thromboprophylaxis in ambulatory APC is a pragmatic evidence-based approach trying to deal with a serious cancer related complication that affects these patients. It is expected that data from further randomised trials (e.g SELECT-D and CASSINI) will provide further evidence in this area.
The European Society of Cardiology (ESC) has proposed an updated risk stratification model for de... more The European Society of Cardiology (ESC) has proposed an updated risk stratification model for death in patients with acute pulmonary embolism based on clinical scores (Pulmonary Embolism Severity Index (PESI) or simplified PESI (sPESI)), right ventricle dysfunction (RVD) and elevated serum troponin (2014 ESC model).We assessed the ability of the 2014 ESC model to predict 30-day death after acute pulmonary embolism. Consecutive patients with symptomatic, confirmed pulmonary embolism included in prospective cohorts were merged in a collaborative database. Patients’ risk was classified as high (shock or hypotension), intermediate-high (RVD and elevated troponin), intermediate-low (RVD or increased troponin or none) and low (sPESI 0). Study outcomes were death and pulmonary embolism-related death at 30 days.Among 906 patients (mean±sd age 68±16, 489 females), death and pulmonary embolism-related death occurred in 7.2% and 4.1%, respectively. Death rate was 22% in “high-risk” (95% CI 14...
We examined the impact of sentinel lymph node (SLN) biopsy among patients with primary melanoma t... more We examined the impact of sentinel lymph node (SLN) biopsy among patients with primary melanoma that exceeded 4.0 mm in Breslow thickness, treated in our Institution from 1998 until 2009. According to Kaplan-Meier statistics, overall survival (OS) and disease-free survival (DFS) were assessed in patients with: i) disseminated disease at diagnosis with respect to patients undergoing SLN biopsy and ii) positive SLN and negative SLN. The effect of age, thickness and number of positive SLN on survival was also calculated. Forty-three patients with thick melanoma were included (29 men and 14 women; mean age 65 ± 17 years, tumor thickness ranging from 4 to 20 mm). Thirteen patients (30%) were not eligible for SLN biopsy due to metastatic disease or poor clinical condition. Biopsy was performed on 30 patients: 14 with positive SLN (46.7%, group A) and 16 with negative SLN (53.3%, group B). Seven patients (50%) died in group A and 2 patients (13%) in group B (mean follow-up 28 and 59 months...
Combined antiplatelet and anticoagulant therapy has been suggested for those clinical conditions ... more Combined antiplatelet and anticoagulant therapy has been suggested for those clinical conditions in which conventional antithrombotic regimens have shown suboptimal efficacy, and in patients with indication for both: antiplatelet and anticoagulant therapy. Clinical trials aimed at assessing the clinical benefit of the association with respect to mono-therapy have been conducted in patients with atrial fibrillation, in patients with recent myocardial infarction, and in patients with prosthetic heart valves. Overall, a favorable benefit-risk profile of combined therapy in comparison to anticoagulant alone has been observed in patients with mechanical prosthetic heart valves and in those with coronary artery disease while no clear advantage has been shown in patients with atrial fibrillation. In almost all these studies, however, a higher risk of major bleeding has been observed in patients receiving combined therapy in comparison to patients receiving warfarin alone. Thus, a combined regimen of anticoagulant and antiplatelet therapy should be reserved for selected patients at high risk of thromboembolic events who have a low risk of bleeding.
Introduction: Direct oral anticoagulants (DOACs) are increasingly used for anticoagulation or pre... more Introduction: Direct oral anticoagulants (DOACs) are increasingly used for anticoagulation or prevention of thromboembolic events in conditions that may co-occur with pregnancy. However, evidence regarding efficacy and safety during pregnancy is scarce. Aim: To review the current literature concerning the efficacy, safety and outcome of DOACs during pregnancy in humans. Methods: We systematically searched the MedLine public database for all studies describing the use of DOACs during pregnancy published up to July 4th 2017. Results: 236 cases of DOAC use during pregnancy were reported. Rivaroxaban was the most reported DOAC (n = 178). DOACs were mostly used for prophylaxis or treatment of venous thromboembolism (n = 91). DOACs were discontinued within the first 2 months of pregnancy in 84%, maximum reported duration of use was 26 weeks. Pregnancy outcome data were available for 140 pregnancies. Thirty-nine pregnancies were electively terminated. In the remaining 101 pregnancies total miscarriage rate was 31% (n = 31) and live birth rate was 68% (n = 69, 1 missing). Foetal and neonatal abnormalities were reported in 8 pregnancies, of which at least half were suspected to be related to rivaroxaban use during the 1st trimester of pregnancy. In only 18% of cases (n = 42), the presence or absence of thrombotic and bleeding complications was reported. Conclusion: The limited available evidence raises concern regarding embryo-foetal safety, with high incidence of miscarriages and a 4% rate of anomalies with the use of rivaroxaban. Not enough data are available to judge safety and efficacy of the use of DOACs during pregnancy.
BACKGROUND: Direct oral anticoagulants (DOAs) have been shown to be as eff ective and at least as... more BACKGROUND: Direct oral anticoagulants (DOAs) have been shown to be as eff ective and at least as safe as conventional anticoagulation for the prevention of recurrences in patients with VTE. Whether this is the case in patients with cancer-associated VTE remains undefi ned. METHODS: We performed a meta-analysis of randomized controlled trials with the aim of assessing the effi cacy and safety of DOAs in patients with VTE and cancer. MEDLINE, EMBASE, and CENTRAL were searched up to December 2013 with no language restriction. Th e primary outcome of the analysis was recurrent VTE. Data on major bleeding (MB) and clinically relevant nonmajor bleeding were analyzed. Data were pooled and compared by ORs and 95% CIs. RESULTS: Overall, 10 studies comparing DOAs with conventional anticoagulation for treatment of VTE including patients with cancer were included in the review. Six studies were included in the meta-analysis (two with dabigatran, two with rivaroxaban, one with edoxaban, and one with apixaban), accounting for a total of 1,132 patients. VTE recurred in 23 of 595 (3.9%) and in 32 of 537 (6.0%) patients with cancer treated with DOAs and conventional treatment, respectively (OR, 0.63; 95% CI, 0.37-1.10; I 2 , 0%). MB occurred in 3.2% and 4.2% of patients receiving DOAs and conventional treatment, respectively (OR, 0.77; 95% CI, 0.41-1.44; I 2 , 0%). CONCLUSIONS: DOAs seem to be as eff ective and safe as conventional treatment for the prevention of VTE in patients with cancer. Further clinical trials in patients with cancer-associated VTE should be performed to confi rm these results.
Journal of Hepato-Biliary-Pancreatic Sciences, 2014
Laparoscopic cholecystectomy (LC) has largely replaced conventional cholecystectomy in the past d... more Laparoscopic cholecystectomy (LC) has largely replaced conventional cholecystectomy in the past decade. However, there are still limited data about the value of prophylactic sub-hepatic drainage for elective uncomplicated LC. We carried out a systematic review of the literature in order to perform a meta-analysis about this issue. An unrestricted search in MEDLINE, EMBASE and Cochrane Library up to 31 December 2013 was performed. Overall, seven high-methodological quality randomized controlled trials (RCTs) were included in the meta-analysis, resulting in 1310 patients totally. The incidence of abdominal collections, wound infection and overall mortality according to the presence or absence of the sub-hepatic drainage were meta-analyzed. Sub-hepatic drainage showed an increase in the abdominal collection rate in patients who underwent elective uncomplicated LC (OR 1.56, 95% CI 1.00-2.43) if compared to patients without drainage. A non-significant correlation was found in overall mortality and infection rates. The meta-analysis shows that the presence of the sub-hepatic drainage does not reduce the incidence of abdominal collection after uncomplicated LC, whereas it does not influence wound infection and mortality rates, postoperative pain and hospital stay.
Heparin, fondaparinux and vitamin K antagonists (VKAs) are effective for the prevention and treat... more Heparin, fondaparinux and vitamin K antagonists (VKAs) are effective for the prevention and treatment of venous thromboembolism. VKAs reduce by almost 60% the rate of cardioembolic complications in patients with atrial fibrillation. The risk for bleeding and the inconvenience for laboratory monitoring, dose adjustment and drug or food interactions are the main limits for VKAs while parenteral administration is the main limit for heparin and fondaparinux. New oral anticoagulants with more predictable anticoagulant response and no need for laboratory monitoring have been shown to be effective for the prevention and treatment of venous thromboembolism and for the prevention of stroke and systemic embolism in patients with atrial fibrillation. The pharmacokinetic and pharmacodynamic profile of the new agents differ for mechanisms of actionmainly anti Xa and one antithrombin agent-bioavailability, half life, renal or live clearance. Drug interactions have been described with the new agents and inhibitors or inducers of P-gp or CYP3A4. Overall, in the prevention of venous thromboembolism after major elective orthopaedic surgery dabigatran was shown to be non-inferior, rivaroxaban and apixaban to be superior to enoxaparin. Both, rivaroxaban and dabigatran were shown to be non-inferior to low-molecular weight heparin and VKAs for the treatment of venous thromboembolism. Dabigatran 150 mg twice daily reduced the incidence of both ischemic and hemorrhagic stroke in patients with atrial fibrillation respect to warfarin. In these patients rivaroxaban and apixaban reduced the incidence of hemorrhagic stroke with a similar incidence of ischemic stroke. No bleeding concern emerged with the new anticoagulant agents in this indication.
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Papers by Maria Vedovati