Apixaban for the Treatment of Venous Thromboembolism Associated with Cancer.

BACKGROUND: Recent guidelines recommend consideration of the use of oral edoxaban or rivaroxaban for the treatment of venous thromboembolism in patients with cancer. However, the benefit of these oral agents is limited by the increased risk of bleeding associated with their use. METHODS: This was a multinational, randomized, investigator-initiated, open-label, noninferiority trial with blinded central outcome adjudication. We randomly assigned consecutive patients with cancer who had symptomatic or incidental acute proximal deep-vein thrombosis or pulmonary embolism to receive oral apixaban (at a dose of 10 mg twice daily for the first 7 days, followed by 5 mg twice daily) or subcutaneous dalteparin (at a dose of 200 IU per kilogram of body weight once daily for the first month, followed by 150 IU per kilogram once daily). The treatments were administered for 6 months. The primary outcome was objectively confirmed recurrent venous thromboembolism during the trial period. The principal safety outcome was major bleeding. RESULTS: Recurrent venous thromboembolism occurred in 32 of 576 patients (5.6%) in the apixaban group and in 46 of 579 patients (7.9%) in the dalteparin group (hazard ratio, 0.63; 95% confidence interval [CI], 0.37 to 1.07; P<0.001 for noninferiority). Major bleeding occurred in 22 patients (3.8%) in the apixaban group and in 23 patients (4.0%) in the dalteparin group (hazard ratio, 0.82; 95% CI, 0.40 to 1.69; P = 0.60). CONCLUSIONS: Oral apixaban was noninferior to subcutaneous dalteparin for the treatment of cancer-associated venous thromboembolism without an increased risk of major bleeding. (Funded by the Bristol-Myers Squibb-Pfizer Alliance; Caravaggio ClinicalTrials.gov number, NCT03045406.).

Updated meta-analysis on prevention of venous thromboembolism in ambulatory cancer patients.

Randomized clinical trials have evaluated the role of anticoagulants in the prevention of venous thromboembolism (VTE) in ambulatory cancer patients treated with chemotherapy. This meta-analysis is aimed at providing an updated evaluation of the efficacy and safety of anticoagulant prophylaxis in this clinical setting. Medline and Scopus were searched to retrieve randomized controlled trials on the prevention of VTE in ambulatory cancer patients. Two groups of trials were identified with VTE or death as the primary outcome, respectively. VTE was the primary outcome of this analysis. Anticoagulant prophylaxis reduced the incidence of VTE in studies in which the primary outcome was VTE [14 studies, 8,226 patients; odds ratio (OR)=0.45; 95% confidence interval (95% CI): 0.36-0.56] or death (8 studies, 3,727 patients; OR=0.61; 95% CI: 0.47-0.81). When these studies were pooled together, VTE was reduced by 49% (95% CI: 0.43-0.61) with no significant increase in major bleeding (OR=1.30, 95% CI: 0.98-1.73). The risk of major bleeding was increased in studies with VTE as the primary outcome (OR=1.43, 95% CI: 1.01-2.04). Similar reductions of VTE were observed in studies with parenteral (OR=0.43, 95% CI: 0.33-0.56) or oral anticoagulants (OR=0.49, 95% CI: 0.33-0.74). The reduction in VTE was confirmed in patients with lung (OR=0.42, 95% CI: 0.26-0.67) or pancreatic cancer (OR=0.26, 95% CI: 0.14-0.48), in estimated high-risk patients, in high-quality studies and with respect to symptomatic VTE. In conclusion, prophylaxis with oral or parenteral anticoagulants reduces the risk of VTE in ambulatory cancer patients, with an acceptable increase in major bleeding.

Reversal of dabigatran-associated bleeding using idarucizumab: review of the current evidence.

Major bleeding occurs in about 4% of patients while on treatment with direct oral anticoagulants (DOACs). The case-fatality rate associated with these events is estimated to be about 5%. The specific roles of antidotes, when used with DOACs in reducing the case fatality or improving the overall clinical course of these events, are not thoroughly understood. To this regard, the US Food and Drug Administration as well as European Medicines Agency have recently licensed idarucizumab for the management of patients with life-threatening bleeding or the need for urgent surgery/procedures while on treatment with dabigatran. Specifically, idarucizumab is a humanized monoclonal antibody fragment that rapidly reverses the anticoagulant effect of dabigatran. Two other antidotes, andeXanet and ciraparantag are currently under evaluation for reversal of DOACs. Here, we report on the use of idarucizumab in two patients who experienced life-threatening bleeding while on treatment with dabigatran for atrial fibrillation and provide a review highlighting the need for antidotes use with DOACs.

Safety and effectiveness of oral anticoagulants in patients with atrial fibrillation and stage 4 chronic kidney disease: a real-world experience.

It is still uncertain whether direct oral anticoagulants (DOACs) perform better than vitamin K antagonists (VKAs) in subjects with non-valvular atrial fibrillation (NVAF) and advanced chronic kidney disease (CKD). The aim of the study was to compare safety and effectiveness of DOACs and VKAs in patients with NVAF and stage 4 CKD (creatinine clearance 15-29 mL/min). We searched the hospital databases of two academic centers to retrospectively identify patients with stage 4 CKD who were on treatment with DOACs or VKAs for NVAF. Safety was the primary outcome of the study and was assessed in terms of incidence of major bleeding (MB). Secondary outcomes were clinically relevant non-major bleeding (CRNMB) and death for any cause. A total of 176 patients (102 on DOACs and 74 on VKAs) were found and included in the analysis. The incidence rate of MB was not statistically different between groups (8.6 per 100 patients-year in the DOAC group and 5.6 per 100 patients-year in the VKA group). Rates of IS/SSE and CRNMB were statistically similar in the two treatment groups, as well. There were less deaths for any cause in the DOAC group than in the VKA group (8.6 and 15.8 per 100 patients-year, respectively), but the difference was not statistically significant. This study found no difference in terms of safety and effectiveness between patients with NVAF and stage 4 CKD treated with DOACs and VKAs. Larger prospective or randomized studies are needed to confirm these findings.

Bleeding risk with concomitant administration of VEGF-TKIs and anticoagulant agents.

Anti-cancer treatment is considered an independent risk factor for emergent bleeding during anticoagulant treatment in patients with cancer-associated thrombosis. This increased bleeding risk is perceived as major concern particularly when tyrosine kinase inhibitors (TKIs) targeting the vascular endothelial derived growth factor receptor (VEGFR-TKIs) are co-administered with anticoagulants. We evaluated the effects of the combined administration of a VEGF-TKI and the oral direct anticoagulant (apixaban) or the low-molecular weight-heparin dalteparin in a sub-analysis of the Caravaggio study in patients with a diagnosis of cancer patients with venous thromboembolism. The rate of major bleeding was 4.2% in the 668 patients who received any type of anti-cancer treatment and 3.5% in the 487 patients who did not receive any anti-cancer treatment. The relative risk for patients treated with a VEGF-TKI was 1.58 (95% CI: 0.69-3.68), compared to patients treated with anticancer agents other than a VEGF-TKI and 1.73 (95% CI: 0.73-4.07) compared to patients who did not receive any anticancer treatment. The administration of a VGEF-TKI did not have any impact on the recurrence rate of venous thromboembolism. We observed a numerically not statistically significant increase in major bleeding events in patients on concurrent VEGF-TKI and therapeutic anticoagulation with no excess in those who received apixaban. Further prospective well-designed studies are needed to evaluate whether the concomitant administration of VGEF-TKI and anticoagulant agents may result in an increase of bleeding in patients with a diagnosis of cancer treated for venous thromboembolism.

Unmet clinical needs in the prevention and treatment of cancer-associated venous thromboembolism.

Venous thromboembolism (VTE), which includes pulmonary embolism and deep vein thrombosis, is a leading cause of morbidity and mortality in patients with cancer. Based on accumulating evidence, the prophylaxis and treatment of cancer-associated VTE have been changed over the years. Recently, the introduction in clinical practice of the direct oral anticoagulants has radically changed the management of cancer-associated VTE for their easier use and non-inferior efficacy-safety profile compared to low-molecular-weight heparins. However, the heterogeneity of the cancer population in terms of site, type and stage of the malignancy, the presence of comorbidities, and the variability in cancer treatment and prognosis represent major challenges in the management of VTE in patients with cancer. In the present review, we will discuss clinical questions that represent unsolved issues in the setting of cancer-associated VTE and provide an overview on recent evidence on this topic: primary prophylaxis in ambulatory cancer patients treated with chemotherapy and in cancer surgical patients, need of long-term anticoagulation in cancer patients, treatment of VTE in cancer patients at increased bleeding risk and in special categories such as incidental VTE, splanchnic vein thrombosis or catheter-related thrombosis.

Ambulatory cancer patients: who should definitely receive antithrombotic prophylaxis and who should never receive.

Up to 15-20% of cancer patients experience one or more episodes of venous thromboembolism during cancer disease. Approximately 80% of all cancer-associated venous thromboembolic events occur in non-hospitalized patients. Routine thromboprophylaxis for outpatients with cancer who start new anticancer treatment is currently not recommended by the international guidelines due to the high heterogeneity of these patients in terms of VTE or bleeding risks, the difficulties in selecting patients at high risk, and the uncertainty of duration of prophylaxis. Although the international guidelines endorsed the Khorana score for estimating the thrombotic risk in ambulatory cancer patients, the discriminatory performance of this score is not completely convincing and varies according to the cancer type. Consequently, a minority of ambulatory patients with cancer receive an accurate screening for primary prophylaxis of VTE. The aim of this review is to provide support to physicians in identifying those ambulatory patients with cancer for whom thromboprophylaxis should be prescribed and those that should not be candidate to thromboprophylaxis. In absence of high bleeding risk, primary thromboprophylaxis should be recommended in patients with pancreatic cancer and, probably, in patients with lung cancer harboring ALK/ROS1 translocations. Patients with upper gastrointestinal cancers are at high risk of VTE, but a careful assessment of bleeding risk should be made before deciding on antithrombotic prophylaxis. Primary prevention of VTE is not recommended in cancer patients at increased risk of bleeding as patients with brain cancer, with moderate-to-severe thrombocytopenia or severe renal impairment.

Recurrent venous thromboembolism and major bleeding in patients with localised, locally advanced or metastatic cancer: an analysis of the Caravaggio study.

BACKGROUND: Patients with cancer-associated venous thromboembolism (VTE) have a high risk of VTE recurrence and anticoagulant treatment-related bleeding, but the correlation of these risks with the cancer stage is unclear. METHODS: We evaluated the risks of VTE recurrence and treatment-related major bleeding according to the cancer stage in patients with VTE and solid cancer randomised to apixaban or dalteparin in the Caravaggio study. Cancer stage was categorised by expert cancer physicians according to pre-specified criteria, and study outcomes were adjudicated by an independent committee unaware of cancer stage and treatment allocation. RESULTS: Of the 1034 patients included in this analysis, 217 (21.0%) had localised cancer, 279 (27.0%) locally advanced cancer and 503 (48.7%) metastatic cancer. Cancer stage was undetermined in 35 patients (3.4%). VTE recurrence and major bleeding rates were 2.8% and 3.2% in patients with localised cancer, respectively. In comparison to patients with localised cancer, the VTE recurrence rate was higher in patients with locally advanced cancer (7.5%, hazard ratio [HR] = 2.8, 95% confidence interval [CI] = 1.1-6.9) and metastatic cancer (8.7%, HR = 3.3, CI = 1.4-7.7, CI). Patients with metastatic cancer had numerically increased major bleedings compared to those with localised cancer (5.2%, HR = 1.65, CI = 0.7-3.8). The efficacy and safety of apixaban and dalteparin across patients with different cancer stages were consistent with the findings observed in the overall patients with cancer randomised in the study. CONCLUSIONS: Patients with locally advanced and metastatic cancer have a higher rate of VTE recurrence than patients with localised cancer with no statistically significant difference in treatment-related major bleeding.

Do Antiangiogenics Promote Clot Instability? Data from the TESEO Prospective Registry and Caravaggio Clinical Trial.

BACKGROUND: Venous thromboembolism (VTE) is a common complication in cancer patients. Much of its morbidity stems from the development of fatal pulmonary embolisms (PE). Little is known about the factors involved in clot stability, with angiogenesis possibly being implicated. METHODS: The database is from the TESEO prospective registry that recruits cancer patients with VTE from 41 Spanish hospitals. Independent validation was conducted in a cohort from the Caravaggio trial. The objective is to evaluate the association between exposure to antiangiogenic therapies and the PE/VTE proportion in oncological patients. RESULTS: In total, 1,536 subjects were evaluated; 58.4% (n = 894) had a PE and 7% (n = 108) received antiangiogenic therapy (bevacizumab in 75%). The PE/VTE proportion among antiangiogenic-treated individuals was 77/108 (71.3%) versus 817/1,428 (57.2%) among those receiving other alternative therapies (p = 0.004). The effect of the antiangiogenics on the PE/VTE proportion held up across all subgroups except for active smokers or those with chronic obstructive pulmonary disease. Exposure to antiangiogenics was associated with increased PEs, odds ratio (OR) 2.27 (95% CI, 1.42-3.63). In the Caravaggio trial, PE was present in 67% of the individuals treated with antiangiogenics, 50% of those who received chemotherapy without antiangiogenic treatment, and 60% without active therapy (p = 0.0016). CONCLUSION: Antiangiogenics are associated with increased proportion of PE in oncological patients with VTE. If an effect on clot stability is confirmed, the concept of thrombotic risk in cancer patients should be reconsidered in qualitative terms.

Chemotherapy-associated thromboembolic risk in cancer outpatients and effect of nadroparin thromboprophylaxis: results of a retrospective analysis of the PROTECHT study.

BACKGROUND: Cancer patients receiving chemotherapy are at increased risk of thrombosis. Nadroparin has been demonstrated to reduce the incidence of venous and arterial thrombotic events (TEs) by about 50% in cancer outpatients receiving chemotherapy. The aims of this retrospective analysis were to evaluate the thromboembolic risk and the benefit of thromboprophylaxis according to type of chemotherapy. METHODS: Cancer outpatients were randomly assigned to receive subcutaneous injections of nadroparin or placebo. The incidence of symptomatic TEs was assessed according to the type of chemotherapy. Results were reported as risk ratios with associated 95% CI and two-tailed probability values. RESULTS: 769 and 381 patients have been evaluated in the nadroparin and placebo group, respectively. In the absence of thromboprophylaxis, the highest rate of TEs was found in patients receiving gemcitabine- (8.1%) or cisplatin-based chemotherapy (7.0%). The combination of gemcitabine and cisplatin or carboplatin increased the risk to 10.2%. Thromboprophylaxis reduced TE risk by 68% in patients receiving gemcitabine; with a further decrease to 78% in those receiving a combination of gemcitabine and platinum. CONCLUSIONS: This retrospective analysis confirms that patients undergoing chemotherapy including gemcitabine, platinum analogues or their combination are at higher risk of TEs. Our results also suggest that outpatients receiving chemotherapy regimens including these agents might achieve an increased benefit from thromboprophylaxis with nadroparin. CLINICAL TRIAL REGISTRATION NUMBER: NCT 00951574.

Risk factors and one-year mortality in patients with direct oral anticoagulant-associated gastrointestinal bleeding.

BACKGROUND AND AIM: Risk factors and mortality in patients with DOACs-associated gastrointestinal bleeding (GIB) are not completely defined. Aims of this study were to identify risk factors for bleeding and evaluate one-year mortality in patients with DOACs-associated GIB. METHODS: We conducted a case-control study. Cases were patients with DOACs-associated GIB admitted to the Perugia Hospital, Italy between 2013 and 2019. Controls were derived from the prospective database of patients with DOACs referred to the ambulatory service. Cases and controls were matched by a 1:2 ratio for type and dose of DOAC, indication for anticoagulation and gender. Univariate and multivariable analyses were performed to identify risk factors. Hazard Ratio with 95% confidence interval was used to calculate mortality. RESULTS: We included 324 patients, of which 108 with DOACs-associated GIB. Mean age was 81.9 ± 7.2 years and 78.9 ± 8.7 years, respectively. The most frequent indication for anticoagulation was atrial fibrillation. Reduced doses of DOACs were prescribed in 186 patients (56.4%). At multivariable analysis, active cancer (OR:7.26; 95%CI 3.10-16.96), renal impairment (OR:4.26; 95%CI 1.98-9.17), bleeding predisposition (OR:3.66; 95%CI 2.00-6.68), COPD (OR:2.12; 95%CI 1.08-4.16) and uncontrolled hypertension (OR:1.86; 95%CI 1.07-3.23) were found to be predictors for DOACs-associated GIB. Adjusted one-year mortality was significantly higher in patients who experienced GIB compared with those who did not experience GIB (OR: 7.04; 95%CI 3.82-14.31). CONCLUSIONS: Predictors of DOACs-associated GIB included active cancer, renal impairment, bleeding predisposition, COPD and uncontrolled hypertension. The adjusted one-year-mortality was significantly increased in patients with DOACs-associated GIB in comparison to DOACs patients without GIB.

Effects of concomitant administration of anticancer agents and apixaban or dalteparin on recurrence and bleeding in patients with cancer-associated venous thromboembolism.

BACKGROUND: Whether concomitant administration of anticancer agents influences the efficacy and safety of oral anticoagulants in patients treated for cancer-associated venous thromboembolism (VTE) is undefined. The pharmacological interaction between anticancer agents and direct oral anticoagulants is perceived as a concern. METHODS: We evaluated the effects of concomitant administration of anticancer agents on recurrent VTE, major bleeding and death in patients with cancer-associated VTE randomised to receive apixaban or dalteparin in the Caravaggio study. RESULTS: Anticancer agents were concomitantly given to 336 patients (58.3%) treated with apixaban and to 332 patients (57.3%) treated with dalteparin. In patients treated with apixaban, recurrent VTE occurred in 20 (6.0%) and 12 (5.0%) among patients treated or not treated with anticancer agents, respectively (hazard ratio [HR] = 1.14; 0.55-2.38); major bleeding occurred in 12 (3.6%) and 10 (4.2%) patients , respectively (HR = 0.79; 0.34-1.82), and death occurred in 74 (22.0%) and 61 (25.4%) patients , respectively (HR = 0.71; 0.51-1.00). In patients treated with dalteparin, recurrent VTE occurred in 24 (7.2%) and 22 (8.9%) among patients treated or not treated with anticancer agents, respectively (HR = 0.71; 0.40-1.28); major bleeding occurred in 16 (4.8%) and 7 (2.8%) patients, respectively (HR = 1.78; 0.66-4.79), and death occurred in 87 (26.2%) and 66 (26.7%) patients, respectively (HR = 0.85; 0.62-1.18). The comparative efficacy and safety of apixaban and dalteparin was not different in patients treated or not treated with anticancer agents. No effect on recurrent VTE, major bleeding or death was observed with inhibitors or inducers of P-glycoprotein and/or CYP3A4. CONCLUSION: In our study, concomitant administration of anticancer agents had no effect on the risk of VTE recurrence or major bleeding in patients treated with apixaban or dalteparin for cancer-associated VTE.

Nadroparin for the prevention of thromboembolic events in ambulatory patients with metastatic or locally advanced solid cancer receiving chemotherapy: a randomised, placebo-controlled, double-blind study.

BACKGROUND: Clinical trials are needed to assess the clinical benefit of antithrombotic prophylaxis in patients with cancer who are receiving chemotherapy, since these patients are at an increased risk of developing a thromboembolism. We did a trial to assess the clinical benefit of the low-molecular-weight heparin nadroparin for the prophylaxis of thromboembolic events in ambulatory patients receiving chemotherapy for metastatic or locally advanced solid cancer. METHODS: Between October, 2003, and May, 2007, ambulatory patients with lung, gastrointestinal, pancreatic, breast, ovarian, or head and neck cancer were randomly assigned in a double-blind manner to receive subcutaneous injections of nadroparin (3800 IU anti-Xa once a day, n=779) or placebo (n=387), in a 2:1 ratio. Study treatment was given for the duration of chemotherapy up to a maximum of 4 months. The primary study outcome was the composite of symptomatic venous or arterial thromboembolic events, as assessed by an independent adjudication committee. All randomised patients who received at least one dose of study treatment were included in the efficacy and safety analyses (modified intention-to-treat population). The study is registered with ClinicalTrials.gov, NCT 00951574. FINDINGS: 1150 patients were included in the primary efficacy and safety analyses: 769 patients in the nadroparin group and 381 patients in the placebo group. 15 (2.0%) of 769 patients treated with nadroparin and 15 (3.9%) of 381 patients treated with placebo had a thromboembolic event (single-sided p=0.02). Five (0.7%) of 769 patients in the nadroparin group and no patients in the placebo group had a major bleeding event (two-sided p=0.18). The incidences of minor bleeding were 7.4% (57 of 769) with nadroparin and 7.9% (30 of 381) with placebo. There were 121 (15.7%) serious adverse events in the nadroparin goup and 67 (17.6%) serious adverse events in the placebo group. INTERPRETATION: Nadroparin reduces the incidence of thromboembolic events in ambulatory patients with metastatic or locally advanced cancer who are receiving chemotherapy. Future studies should focus on patients who are at a high risk for thromboembolic events. FUNDING: Italfarmaco SpA, Milan, Italy.

Treatment of venous thromboembolism in patients with cancer: from clinical trials to real life.

Approximately one-fifth of all cases of venous thromboembolism (VTE) are related to cancer. VTE complications may have a substantial impact on prognosis, quality of life and care in patients with cancer. Patients with cancer-related VTE are at increased risk of developing recurrent VTE compared to patients without cancer, but also have a higher risk of major bleeding. In the last years, direct oral anticoagulants (DOACs) have been evaluated in a head-to-head comparison with low molecular weight heparin (LMWH) in two randomized trials for the long-term treatment of VTE in patients with advanced cancer. The results of these trials show that DOACs have a similar efficacy profile, but probably higher risk of bleeding, compared to LMWH dalteparin. Because DOACs offer a simple oral treatment regimen without the need for anticoagulation monitoring, they could be attractive alternatives to LMWHs in these setting. The American Society of Clinical Oncology guidelines, published in August 2019, recommend LMWH, edoxaban and rivaroxaban as first-choice therapies for long-term anticoagulation in cancer patients with VTE. However, several practical issues should be considered concerning the long-term use of DOAC treatment in patients with cancer. Major concerns have been highlighted about the gastrointestinal bleeding risk in patients with gastrointestinal cancers and the potential drug-drug interactions in combination for some specific anticancer therapies. Several studies comparing DOACs with LMWH are currently ongoing to refine our knowledge concerning treatment with DOACs in patients with cancer-associated VTE.

Management of venous thromboembolism in cancer patients: Considerations about the clinical practice guideline update of the American society of clinical oncology.

The American Society of Clinical Oncology (ASCO) recently updated their clinical practice guidelines. The most novel aspect of this update is represented by the introduction of DOACs as pharmacological options both for prophylaxis and treatment of VTE in patients with cancer. The heterogeneity of the cancer population in terms of type and stage of the malignancy, presence of comorbidities, and variability in cancer treatments and prognosis represent the major challenge of managing VTE in patients with cancer. The use of VTE prophylaxis is currently recommended in cancer patients admitted to the hospital for an acute illness or reduced mobility, but no sufficient information is available on the risk of bleeding during thromboprophylaxis. Concerning the thromboprophylaxis in ambulatory cancer patients receiving chemotherapy, further refinement of existing risk models or development of new models are needed for improving risk stratification to identify high-risk cancer patients. The updated ASCO guidelines recommend the use of DOACs (edoxaban and rivaroxaban) for treatment of VTE in patients with cancer. However, Major concerns on "real-life" use of DOACs in patients with cancer are highlighted especially for the bleeding risk in patients with gastrointestinal cancers and the potential drug-drug interactions with specific anticancer therapies. CONCLUSIONS: Uncertainties to the updated ASCO guidelines remain concerning a number of indications on prophylaxis and treatment due to the limited evidence available. These limitations determine the low strength of the recommendations. The ongoing studies will contribute to refine the best management of patients with cancer-associated VTE.

Seasonal variation in the occurrence of venous thromboembolism: data from the MASTER Registry.

Many studies showed that the occurrence of cardiovascular and cerebrovascular events exhibits a seasonal variation. As for venous thromboembolism (VTE), not univocal results are available, and studies are mainly retrospective. We aimed to confirm the existence of a seasonal pattern in the occurrence of VTE on a large prospective population. The analysis considered consecutive cases of VTE enrolled into the MASTER Registry in 25 Italian hospitals, between January 2002 and November 2004. The total population consisted of 2119 subjects (1056 men, mean age 59 +/- 18 years). The total sample was divided into subgroups by gender, age (<40, 41-60, 61-80, > or = 80 years), type of event (first episode; proximal or distal; upper or lower limb; idiopathic or secondary deep vein thrombosis or pulmonary embolism, or both), and underlying risk factors, eg, cancer, previous VTE, estroprogestinic therapy, lack of prophylaxis, immobilization, surgery, pregnancy or puerperium, and medical diseases. Cases were grouped according to season and month of occurrence, and the data were analyzed by either the chi(2) test for goodness of fit and chronobiological analysis. VTE was most frequent in Autumn and less frequent in Spring (32.9% vs 19%, respectively, chi(2) = 90.62; P < .001). This pattern was shown for most subgroups. Chronobiological analysis identified a significant rhythmic annual pattern, with a main September-October peak for several subgroups (men, age 41-60 and 61-80 years, secondary event, previous VTE, immobilization), and a trend for most of the others. It is possible that subjects at increased risk could perhaps deserve appropriate or potentiated VTE prophylaxis in certain periods of the year.

Patients aged 90 years or older with atrial fibrillation treated with oral anticoagulants: A multicentre observational study.

BACKGROUND: Patients aged 90 years or older are often excluded from or under-represented in clinical trials and cohort studies. The clinical benefit of anticoagulation in nonagenarians with atrial fibrillation (AF) remains undefined. OBJECTIVES: To assess the effectiveness and safety of oral anticoagulants in AF patients aged 90 years or older. METHODS: Non-valvular AF patients aged 90 years or older receiving direct oral anticoagulants (DOACs) or vitamin K antagonists (VKAs) were included in this observational multicentre study. The primary outcome was the composite of ischaemic stroke/transient ischemic attack (TIA) and systemic embolism (SE). Major bleeding (MB), anticoagulant discontinuation and all-cause death were also assessed. Results are reported as sub-distribution hazard ratios (SHR) with 95% CI, taking death as competing risk. RESULTS: 546 patients were included (301 VKAs retrospective cohort and 245 DOACs prospective cohort; median follow-up 404 days). The rate of ischaemic stroke/TIA/SE was 2.4% patient-year and that of MB 5.5% patient-year. Previous ischaemic stroke/TIA (SHR 3.47; 95% CI 1.54-7.81) and vascular disease (SHR 2.89; 95% CI 1.27-6.60) were independent predictors of ischaemic stroke/TIA/SE. Previous bleeding (SHR 2.53; 95% CI 1.37-4.64) was an independent predictor of MB. The risk of ischaemic stroke/TIA/SE (SHR 0.78, 95% CI 0.30-2.04) or MB (SHR 1.43, 95% CI 0.77-2.65) was not significantly different with DOACs or VKAs. CONCLUSIONS: In AF nonagenarians receiving anticoagulant treatment, the rate of ischaemic stroke/TIA/SE is relatively low with the drawback of a not negligible rate of MB. DOACs seem a reasonable option for prevention of ischaemic stroke/TIA/SE in this setting.

Data on the use of oral anticoagulants in nonagenarians with atrial fibrillation.

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 patients are often excluded from or under-represented in clinical trials and cohort studies.