Evaluation of thromboembolic events in cancer patients receiving bevacizumab according to the Japanese Adverse Drug Event Report database

Purpose We aimed to examine the risk factors, time of onset, incidence rates, and outcomes of thromboembolic events induced by bevacizumab in patients with cancer using the Japanese Adverse Drug Event Report (JADER) database of the Pharmaceuticals and Medical Devices Agency. Methods Adverse event data recorded in the JADER database between January 2004 and January 2015 were used. After screening the data using the generic drug name bevacizumab, patient data were classified into two groups by age and five groups by cancer type. The histories of disorders were also categorized. Arterial thromboembolic event and venous thromboembolic event were classified as “favorable” or “unfavorable” outcomes. Results In total, 6076 patients were reported to have developed adverse events during the sample period, of which 233 and 453 developed arterial thromboembolic event and venous thromboembolic event, respectively. Logistic analysis suggested that the presence of cancer was a significant risk factor for both arterial thromboembolic event and venous thromboembolic event. Age (≥70 years), histories of either hypertension or diabetes mellitus were also risk factors for arterial thromboembolic event. Median cumulative times of onset for arterial thromboembolic event and venous thromboembolic event were 60 and 80 days, respectively, and were not significantly different by the log-rank test. By the chi-square test, the rate of unfavorable outcomes was found to be higher after developing arterial thromboembolic event than after venous thromboembolic event. Conclusion Thromboembolism is a leading cause of mortality in patients with cancer. Patients should be monitored for the symptoms of thromboembolic events right from the initial stages of bevacizumab treatment.

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Thrombosis and the Antiphospholipid Syndrome

Hematology ◽

10.1182/asheducation-2005.1.462 ◽

2005 ◽

Vol 2005 (1) ◽

pp. 462-468 ◽

Cited By ~ 20

Author(s):

Thomas L. Ortel

Keyword(s):

Risk Factors ◽

Antiphospholipid Syndrome ◽

Antiphospholipid Antibodies ◽

Thromboembolic Event ◽

Randomized Clinical Trials ◽

Venous Thromboembolic Event ◽

Thromboembolic Events ◽

Additional Risk ◽

Initial Event ◽

Venous Thromboembolic

Abstract The antiphospholipid syndrome is an antibody-mediated hypercoagulable state characterized by recurrent venous and arterial thromboembolic events. Several studies have determined that the frequency of antiphospholipid syndrome in patients presenting with a venous thromboembolic event is between 4% and 14%. Because of the high risk for recurrent thromboembolism in these patients, current recommendations suggest a longer, potentially lifelong, course of antithrombotic therapy following an initial event. Although most authorities agree on an extended course of therapy, considerable controversy surrounds the optimal target therapeutic INR for patients with antiphospholipid syndrome. For an initial venous thromboembolic event, a target INR of 2.0 to 3.0 is supported by two prospective, randomized clinical trials. In contrast, relatively limited data exist for an initial arterial thromboembolic event in patients who have the antiphospholipid syndrome, and therapeutic recommendations range from aspirin to warfarin with a high target INR. Recurrent thromboembolic events can be extremely difficult to treat, and some patients may benefit from the addition of immunosuppressive therapies. Importantly, as many as 50% of the initial thromboembolic events sustained by patients with antiphospholipid antibodies occur in the setting of additional, coincident prothrombotic risk factors, indicating the importance of addressing any additional risk factors, such as hypercholesterolemia, in these patients. Prospective studies are needed to address the role of thromboprophylactic strategies in asymptomatic individuals with antiphospholipid antibodies in the absence of additional risk factors.

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MLTI-19. VENOUS THROMBOEMBOLIC EVENTS IN PATIENTS WITH BRAIN METASTASES: THE PICOS SCORE

Neuro-Oncology Advances ◽

10.1093/noajnl/vdz014.078 ◽

2019 ◽

Vol 1 (Supplement_1) ◽

pp. i18-i18

Author(s):

Fabian Wolpert ◽

Bettina Grossenbacher ◽

Anna Lareida ◽

Patrick Roth ◽

Marian Neidert ◽

...

Keyword(s):

Risk Factors ◽

Brain Metastasis ◽

Odds Ratio ◽

Thromboembolic Event ◽

Venous Thromboembolic Event ◽

Thromboembolic Events ◽

Primary Tumors ◽

Venous Thromboembolic Events ◽

Venous Thromboembolic ◽

Score Model

Abstract BACKGROUND: Venous thromboembolic events are significant complications in patients and possibly associated with an unfavorable outcome. Thrombosis risk is poorly defined for patients with brain metastasis, and available risk calculation scores are not validated for these patients. METHODS: We identified 811 patients with brain metastasis followed at our institution and screened electronic charts retrospectively for the occurrence of venous thromboembolic events, along with candidate risk factors. Risk factors were tested in uni- and multivariate analyses and finally integrated in a score model for risk prediction. RESULTS: Venous thromboembolic events were documented in 97 of 811 patients (12.0%). Primary tumors with high thrombogenicity (p=0.02, odds ratio 1.7, 95% CI 1.1–2.8), dexamethasone (p=0.011, odds ratio 2.27, 95% CI 1.5–4.5), chemotherapy (p=0.005, odds ratio 3.4, 95% CI 1.6–7.5), BMI > 35 kg/m2 (p=0.002, odds ratio 3.4, 95% CI 1.6–7.5) and immobilization (p=0.003, odds ratio 2.4, 95% CI 1.3–4.3) were confirmed as independent predictors of VTE. We derived a score model for venous thromboembolic event prediction, the PICOS (thrombogenic Primary, Immobilization, Chemotherapy, Obesity, Steroids) score (0–7 points). Receiver Operating Characteristic Curve Analysis demonstrated its prognostic accuracy (AUC=0.71, 95% CI 0.64–0.77), and its predictive capability was superior to that of other scores proposed for the evaluation of venous thromboembolic event risk such as the Khorana (AUC=0.51) or CONKO (AUC=0.52) scores. CONCLUSIONS: We report a rate of venous thrombotic events of 12.0% in our cohort of 811 patients with brain metastasis. We define a risk model for prediction in of venous thrombotic events in patients with BM, the PICOS score. It may become a valuable tool for the identification of brain metastasis patients at high risk for venous thromboembolic events and be helpful for guidance of clinicians towards decision whether to start thrombosis prophylaxis. Further, the PICOS score might be used for stratification in controlled studies.

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P14.25 Venous thromboembolic events in patients with brain metastases: the PICOS score

Neuro-Oncology ◽

10.1093/neuonc/noz126.260 ◽

2019 ◽

Vol 21 (Supplement_3) ◽

pp. iii72-iii72

Author(s):

F Wolpert ◽

B Grossenbacher ◽

A Lareida ◽

P Roth ◽

M C Neidert ◽

...

Keyword(s):

Risk Factors ◽

Brain Metastasis ◽

Odds Ratio ◽

Thromboembolic Event ◽

Venous Thromboembolic Event ◽

Thromboembolic Events ◽

Primary Tumors ◽

Venous Thromboembolic Events ◽

Venous Thromboembolic ◽

Score Model

Abstract BACKGROUND Venous thromboembolic events are significant complications in patients and possibly associated with an unfavorable outcome. Thrombosis risk is poorly defined for patients with brain metastasis, and available risk calculation scores are not validated for these patients. MATERIAL AND METHODS We identified 811 patients with brain metastasis followed at our institution and screened electronic charts retrospectively for the occurrence of venous thromboembolic events, along with candidate risk factors. Risk factors were tested in uni- and multivariate analyses and finally integrated in a score model for risk prediction. RESULTS Venous thromboembolic events were documented in 97 of 811 patients (12.0%). Primary tumors with high thrombogenicity (p=0.02, odds ratio 1.7, 95% CI 1.1–2.8), dexamethasone (p=0.011, odds ratio 2.27, 95% CI 1.5–4.5), chemotherapy (p=0.005, odds ratio 3.4, 95% CI 1.6–7.5), BMI > 35 kg/m2 (p=0.002, odds ratio 3.4, 95% CI 1.6–7.5) and immobilization (p=0.003, odds ratio 2.4, 95% CI 1.3–4.3) were confirmed as independent predictors of VTE. We derived a score model for venous thromboembolic event prediction, the PICOS (thrombogenic Primary, Immobilization, Chemotherapy, Obesity, Steroids) score (0–7 points). Receiver Operating Characteristic Curve Analysis demonstrated its prognostic accuracy (AUC=0.71, 95% CI 0.64–0.77), and its predictive capability was superior to that of other scores proposed for the evaluation of venous thromboembolic event risk such as the Khorana (AUC=0.51) or CONKO (AUC=0.52) scores. CONCLUSION We report a rate of venous thrombotic events of 12.0% in our cohort of 811 patients with brain metastasis. We define a risk model for prediction in of venous thrombotic events in patients with BM, the PICOS score. It may become a valuable tool for the identification of brain metastasis patients at high risk for venous thromboembolic events and be helpful for guidance of clinicians towards decision whether to start thrombosis prophylaxis. Further, the PICOS score might be used for stratification in controlled studies.

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The benefit of EXtending oral antiCOAgulation treatment (EXCOA) after acute cerebral vein thrombosis (CVT): EXCOA-CVT cluster randomized trial protocol

International Journal of Stroke ◽

10.1177/1747493018778137 ◽

2018 ◽

Vol 13 (7) ◽

pp. 771-774 ◽

Cited By ~ 11

Author(s):

Bruno Miranda ◽

Sanjith Aaron ◽

Antonio Arauz ◽

Fernando Barinagarrementeria ◽

Afshin Borhani-Haghighi ◽

...

Keyword(s):

Thromboembolic Event ◽

Cluster Randomized Trial ◽

Venous Thromboembolic Event ◽

Cerebral Vein ◽

Thromboembolic Events ◽

Cerebral Vein Thrombosis ◽

Vein Thrombosis ◽

Venous Thromboembolic Events ◽

Venous Thromboembolic ◽

Cluster Randomized

Rationale After a cerebral vein thrombosis, there is an increased risk of further venous thromboembolic events. The optimal duration of anticoagulation after cerebral vein thrombosis is unknown. Aim To compare efficacy and safety of a policy of short- (3–6 months) versus long-term (12 months) anticoagulation (any type venous thromboembolic events) after cerebral vein thrombosis for the prevention of venous thromboembolic events. Sample size estimates A sample of 1428 patients (749 per arm) allows detecting a reduction from 10 to 5% in the risk of venous thromboembolic event recurrence with 80% power at 5% significance, with 3% dropout rate. Methods and design An international multicenter, prospective cluster-randomized trial with equal allocation between both interventions (ISRCTN25644448). Each cluster is a participating center, which accepted to be randomly allocated to one of the anticoagulation policies. Eligible patients are adults with radiologically confirmed cerebral vein thrombosis within 30 days, and stable to initiate post-acute anticoagulation. Patients judged by the investigator to be an absolute indication for permanent anticoagulation are excluded. Follow-up is at 6, 12 and 24 months. Study outcomes Primary efficacy outcome is any symptomatic and confirmed fatal/nonfatal venous thromboembolic event (recurrent-cerebral vein thrombosis or non-cerebral venous thromboembolic event). Primary safety outcomes include bleeding events during treatment periods and death from any cause. Discussion This study responds to a knowledge gap in the post-acute management of cerebral vein thrombosis patients by comparing short- versus long-term anticoagulation for the prevention of venous thromboembolic event recurrence.

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Comprehensive Study of the Risk Factors for Medication-Related Osteonecrosis of the Jaw Based on the Japanese Adverse Drug Event Report Database

Pharmaceuticals ◽

10.3390/ph13120467 ◽

2020 ◽

Vol 13 (12) ◽

pp. 467

Author(s):

Shinya Toriumi ◽

Akinobu Kobayashi ◽

Yoshihiro Uesawa

Keyword(s):

Risk Factors ◽

Side Effects ◽

Adverse Drug Event ◽

Femoral Fractures ◽

Principal Component ◽

Osteonecrosis Of The Jaw ◽

Drug Event ◽

Event Report ◽

Atypical Femoral Fractures ◽

Antiresorptive Agents

Medication-related osteonecrosis of the jaw (MRONJ) is associated with many drugs, including bisphosphonates (BPs). BPs are associated with atypical femoral fractures and osteonecrosis of the external auditory canal. Thus, many drugs are reported to cause adverse effects on bone. This study aimed to investigate the effects of drugs and patient backgrounds regarding osteonecrosis-related side effects, including MRONJ. This study used a large voluntary reporting database, namely, the Japanese Adverse Drug Event Report database. First, we searched for risk factors related to MRONJ using volcano plots and logistic regression analysis. Next, we searched for bone-necrosis-related side effects using principal component and cluster analysis. Factors that were significantly associated with MRONJ included eight types of BPs and denosumab, prednisolone, sunitinib, eldecalcitol, raloxifene, letrozole, doxifluridine, exemestane, radium chloride, medroxyprogesterone, female, elderly, and short stature. Furthermore, antiresorptive agents (i.e., BPs and denosumab) tended to induce MRONJ and atypical femoral fractures by affecting osteoclasts. We believe these findings will help medical personnel manage the side effects of many medications.

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