The Role of Factor Xa-Independent Pathway and Anticoagulant Therapies in Cancer-Related Stroke

Background: The optimal strategy for stroke prevention in cancer patients is unknown. We compared the underlying mechanisms of coagulopathy and the effects of anticoagulants in patients with active cancer and atrial fibrillation (AF). Methods: We retrospectively enrolled 46 consecutive patients with embolic stroke of unknown source and active cancer (cancer stroke). We consecutively screened patients with cancer patients without stroke (n = 29), AF stroke (n = 52), and healthy subjects (n = 28), which served as controls. Patients with cancer stroke were treated with either enoxaparin (a low-molecular-weight heparin) or a factor Xa inhibitor, and those with AF stroke were treated with factor Xa inhibitors. D-dimer, factor Xa, and circulating cell-free DNA (cfDNA), a marker of neutrophil extracellular traposis, were measured at both before and after anticoagulation. Results: In AF stroke, factor Xa activity and cfDNA and D-dimer levels were decreased by treatment with factor Xa inhibitors. In contrast, in cancer stroke, factor Xa activity was decreased, D-dimer levels were unchanged, and cfDNA levels were increased by treatment with factor Xa inhibitors. In cancer stroke patients treated with enoxaparin, D-dimer levels were decreased (p = 0.011) and cfDNA levels were unchanged. Conclusion: The anticoagulation effects of factor Xa inhibitors differed between cancer stroke and AF stroke.

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Role of Factor Xa Inhibitors in Cancer-Associated Thrombosis: Any New Data?

Advances in Hematology ◽

10.1155/2011/196135 ◽

2011 ◽

Vol 2011 ◽

pp. 1-12 ◽

Cited By ~ 5

Author(s):

Ali Zalpour ◽

Michael H. Kroll ◽

Vahid Afshar-Kharghan ◽

Syed Wamique Yusuf ◽

Carmen Escalante

Keyword(s):

Clinical Trials ◽

Cancer Patients ◽

Anticoagulation Therapy ◽

Factor Xa ◽

Factor Xa Inhibitors ◽

The Us ◽

Prevention And Treatment ◽

Cancer Associated Thrombosis ◽

Current Guidelines

The association between cancer and venous thromboembolism (VTE) has been well documented in the literature. Prevention and treatment of VTE in cancer patients is imperative. Typically, the mainstay regimen for VTE prevention and treatment has been anticoagulation therapy, unless contraindicated. This therapy consists of unfractionated heparin (UFH), low-molecular-weight heparin (LMWH), factor Xa inhibitor, or vitamin K antagonist (VKA). Current guidelines recommend LMWH over VKA for the treatment of VTE in cancer patients. Factor-specific anticoagulants have been proven safe and effective, and recently factor Xa inhibitors have emerged as a treatment alternative to heparins and VKA. Currently, three factor Xa inhibitors have been identified: fondaparinux (the only one approved so far by the US Food and Drug Administration), idraparinux (in clinical trials), and idrabiotaparinux (in clinical trials). This paper will examine the role of these agents, focusing on fondaparinux, for the prevention and treatment of VTE in cancer patients.

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Different D-dimer algorithms to rule out pulmonary embolism in patients with cancer: a comparative study

European Heart Journal Acute Cardiovascular Care ◽

10.1093/ehjacc/zuab020.198 ◽

2021 ◽

Vol 10 (Supplement_1) ◽

Author(s):

BV Silva ◽

C Mendonca ◽

N Cunha ◽

P Silverio Antonio ◽

T Rodrigues ◽

...

Keyword(s):

Pulmonary Embolism ◽

Cancer Patients ◽

Clinical Decision ◽

Pulmonary Angiography ◽

Lower Sensitivity ◽

Vein Thrombosis ◽

Patients With Cancer ◽

D Dimer ◽

Active Cancer ◽

Rule Out

Abstract Funding Acknowledgements Type of funding sources: None. Background Pulmonary embolism (PE) is more prevalent in patients with cancer. D-dimers are a less useful test in such patients due to less specificity. Several algorithms have been developed as an alternative to the fixed d-dimer cutoff, aiming to avoid the excessive use of computed tomography pulmonary angiography (CTPA), but it is not clear which is the most accurate algorithm in PE patients with cancer. Objective To compare the efficacy of 4 algorithms to rule out pulmonary embolism (fixed Ddimer cutoff, age-adjusted, YEARS and PEGed) in patients with active cancer. Methods Retrospective study of consecutive outpatients who presented to the emergency department and underwent CTPA for PE suspicion from April 2019 to February 2020. The clinical-decision algorithms were retrospectively applied. In fixed and age-adjusted cutoffs, high probability patients are directly selected for CTPA and the others perform CTPA if DDimer ≥500µg/L or age x10 µg/L within patients over 50 years, respectively. YEARS includes 3 items (signs of deep vein thrombosis, haemoptysis and whether PE is the most likely diagnosis): patients without any YEARS items and Ddimer ≥1000ng/mL or with ≥1 items and Ddimer 500ng/mL perform CTPA. In the PEGeD, patients with high clinical probability or with intermediate and Ddimer >500µg/L or low probability and Ddimer >1000 µg/L are selected for CTPA. Results Of 409 patients with suspected PE, 87 patients (21,3%) had cancer. The prevalence of PE was 38% in cancer patients and 35% in patients without cancer (p > 0.05). Age-adjusted cut-off, compared to the conventional cutoff, had an AUC significantly higher (0.68 vs 0.61, p = 0.005). Despite both having 100% sensitivity, age-adjusted cutoff had a significant higher specificity compared to conventional cut-off (44% vs 35%, p < 0.05). Both YEARS and PEGED algorithms had significantly lower sensitivity (p = 0.003 and p = 0.002, respectively) and higher specificity (p < 0.001, for both) compared to conventional cutoff in patients with active cancer. The AUC of these two algorithms was not significantly different compared to conventional cutoff (p = 0.08 and p = 0.78, respectively). Conclusion Considering our results, age-adjusted cut-off seems to be the most accurate algorithm to rule out pulmonary embolism in active cancer patients. Sen(%)Spec(%)Conventional10022Age-adjusted10035YEARS9144PEGED9130Abstract Figure. AUC of four algorithms

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Application of Molecular Modeling to Development of New Factor Xa Inhibitors

BioMed Research International ◽

10.1155/2015/120802 ◽

2015 ◽

Vol 2015 ◽

pp. 1-15 ◽

Cited By ~ 17

Author(s):

Vladimir B. Sulimov ◽

Irina V. Gribkova ◽

Maria P. Kochugaeva ◽

Ekaterina V. Katkova ◽

Alexey V. Sulimov ◽

...

Keyword(s):

Molecular Modeling ◽

Factor Xa ◽

Factor Xa Inhibitors ◽

Low Molecular Weight ◽

State University ◽

Thrombin Inhibition ◽

Clotting Cascade ◽

Coagulation Inhibitors

In consequence of the key role of factor Xa in the clotting cascade and absence of its activity in the processes that do not affect coagulation, this protein is an attractive target for development of new blood coagulation inhibitors. Factor Xa is more effective and convenient target for creation of anticoagulants than thrombin, inhibition of which may cause some side effects. This study is aimed at finding new inhibitors of factor Xa by molecular computer modeling including docking SOL and postdocking optimization DISCORE programs. After validation of molecular modeling methods on well-known factor Xa inhibitors the virtual screening of NCI Diversity and Voronezh State University databases of ready-made low molecular weight species has been carried out. Seventeen compounds selected on the basis of modeling results have been tested experimentallyin vitro. It has been found that 12 of them showed activity against factor Xa (IC50= 1.8–40 μM). Based on analysis of the results, the new original compound was synthesized and experimentally verified. It shows activity against factor Xa with IC50value of 0.7 μM.

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Treatment and secondary prevention of venous thromboembolism in cancer patients

Onkologische Welt ◽

10.1055/s-0038-1630173 ◽

2012 ◽

Vol 03 (03) ◽

pp. 121-125

Author(s):

I. Pabinger ◽

C. Ay

Keyword(s):

Clinical Trials ◽

Venous Thromboembolism ◽

Cancer Patients ◽

Oral Anticoagulants ◽

Factor Xa ◽

New Oral Anticoagulants ◽

Phase Iii ◽

Patients With Cancer ◽

Potential Use

SummaryCancer is a major and independent risk factor of venous thromboembolism (VTE). In clinical practice, a high number of VTE events occurs in patients with cancer, and treatment of cancerassociated VTE differs in several aspects from treatment of VTE in the general population. However, treatment in cancer patients remains a major challenge, as the risk of recurrence of VTE as well as the risk of major bleeding during anticoagulation is substantially higher in patients with cancer than in those without cancer. In several clinical trials, different anticoagulants and regimens have been investigated for treatment of acute VTE and secondary prophylaxis in cancer patients to prevent recurrence. Based on the results of these trials, anticoagulant therapy with low-molecular-weight heparins (LMWH) has become the treatment of choice in cancer patients with acute VTE in the initial period and for extended and long-term anticoagulation for 3-6 months. New oral anticoagulants directly inhibiting thrombin or factor Xa, have been developed in the past decade and studied in large phase III clinical trials. Results from currently completed trials are promising and indicate their potential use for treatment of VTE. However, the role of the new oral thrombin and factor Xa inhibitors for VTE treatment in cancer patients still has to be clarified in further studies specifically focusing on cancer-associated VTE. This brief review will summarize the current strategies of initial and long-term VTE treatment in patients with cancer and discuss the potential use of the new oral anticoagulants.

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The potential role of an activity-based guitar program on the anxiety and fulfillment levels of younger relatives of cancer patients: A pilot study

International Journal of Music Education ◽

10.1177/02557614211027316 ◽

2021 ◽

pp. 025576142110273

Author(s):

Erkan Sülün ◽

Hüseyin Olgaçer ◽

Hakkı Cengiz Eren

Keyword(s):

Cancer Patients ◽

Trait Anxiety ◽

Potential Role ◽

Rank Test ◽

Satisfaction Scale ◽

Before And After ◽

Signed Rank Test ◽

Total State ◽

Rank Differences

In this study, the authors evaluated the potential role of an activity-based guitar training program on reducing anxiety and providing fulfillment for younger relatives of cancer patients. Ten active members of KHYD (The Society for Relatives of Cancer Patients), between ages 11 and 17 participated in an 8-week guitar education program. The participants filled out two questionnaires before and after their engagement in the 8-week program, one to measure changes in their anxiety levels (State-Trait Anxiety Inventory) and the other to measure changes in their general fulfillment levels (Multidimensional Students’ Life Satisfaction Scale). Wilcoxon signed rank test, as well as descriptive statistics were used in the analysis of data. Mean rank differences were observed to be statistically significant with respect to total state and trait anxiety scores; in both cases, the participants’ scores decreased after their engagement in the program. Statistically significant mean rank differences were also observed in the overall MSLSS scores and its “friends” and “environment” sub-dimensions; with respect to these, participants’ scores increased after their engagement in the program. Recommendations for more comprehensive, larger-scale studies are given at the end.

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Tinzaparin Safety in Patients With Cancer and Renal Impairment: A Systematic Review

Clinical and Applied Thrombosis/Hemostasis ◽

10.1177/1076029620979592 ◽

2021 ◽

Vol 27 ◽

pp. 107602962097959

Author(s):

I. A. Vathiotis ◽

N. K. Syrigos ◽

E. P. Dimakakos

Keyword(s):

Systematic Review ◽

Molecular Weight ◽

Renal Impairment ◽

Creatinine Clearance ◽

Cancer Patients ◽

Major Bleeding ◽

Severe Renal Impairment ◽

Special Populations ◽

Low Molecular Weight ◽

Patients With Cancer

Low-molecular-weight heparins are approved for primary and secondary venous thromboembolism prevention. Tinzaparin is the low-molecular-weight heparin with the highest average molecular weight. The purpose of this systematic review is to provide an update regarding the safety profile of tinzaparin, prescribed either as a prophylactic or as a therapeutic regimen for venous thromboembolism in special populations, including cancer patients and patients with renal impairment. We identified prospective studies up to August 2020 reporting safety outcomes for cancer patients and patients with renal impairment on tinzaparin regimens. In patients with cancer major bleeding rates fluctuated between 0.8% and 7%. Patients on tinzaparin exhibited significantly lower rates of clinically relevant nonmajor bleeding events in comparison with those on vitamin K antagonists. Bioaccumulation of tinzaparin was not correlated with age, body weight or creatinine clearance. Periodic administration of either prophylactic or therapeutic doses of tinzaparin did not result in bioaccumulation, even in patients with severe renal impairment and creatinine clearance < 20 ml/min. Major bleeding rates for non-cancer patients with renal impairment on prophylactic tinzaparin regimens were 0%. Non-cancer patients with renal impairment on therapeutic tinzaparin regimens exhibited major bleeding in 0 to 3.4% of cases; major bleeding rates were higher for cancer patients with renal impairment on therapeutic tinzaparin regimens (4.3 to 10%). Tinzaparin can be used without dose adjustment in patients with severe renal impairment and creatinine clearance > 20 ml/min. Tinzaparin represents a safe choice for special populations at increased risk for thrombosis and bleeding.

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Concurrent Treatment of VEGFR Tyrosine Kinase Inhibitors (TKIs) and Factor Xa Inhibitors Is Associated with Increased Bleeding Risks

Blood ◽

10.1182/blood-2019-130465 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 3681-3681

Author(s):

Sandip Patel ◽

Tiffany George ◽

Tzu-Fei Wang ◽

Sherry Mori Vogt ◽

Edmund Folefac ◽

...

Keyword(s):

Cancer Patients ◽

Major Bleeding ◽

Metastatic Cancer ◽

Bleeding Event ◽

Factor Xa ◽

Factor Xa Inhibitors ◽

Factor Xa Inhibitor ◽

Bleeding Events ◽

Concurrent Treatment ◽

Clinically Significant

ABSTRACT Background: Some cancer patients with thromboembolism require dual treatment of VEGFR TKIs and factor Xa inhibitors (direct or indirect), which may contribute to increased bleeding risks. However, the safety of such combination treatment has not been well characterized in the literature or national guidelines. Methods: This is a single center retrospective study, where we identified metastatic cancer patients (renal cancer, colorectal cancer, sarcoma, etc) who received concurrent VEGFR TKIs (pazopanib, sunitinib, sorafenib, axitinib, regorafenib, vandetanib, lenvatinib or cabozantinib) and Xa inhibitors (low-molecular weight heparin [LMWH] or direct oral anticoagulants [DOACs] including rivaroxaban or apixaban) at the Ohio State University Medical Center. We assessed bleeding risks of dual therapies vs. factor Xa inhibitors alone, using the same patients as self controls. We reviewed medical charts of all identified patients for clinically significant bleeding events (defined as combined major bleeding and clinically relevant non-major bleeding by the International Society of Thrombosis and Haemostasis criteria). The Cox proportional hazard model was used to compare the differences of time to first clinically significant bleeding event between the groups of concurrent use and anticoagulant use only. Results: A total of 86 patients (26 females and 60 males) were included: 78 Caucasians, 6 African Americans, and 2 others. 81 patients had concurrent TKI and LMWH treatment; 20 patients had concurrent TKI and DOACs; and 85 patients have had been on factor Xa inhibitor alone (LMWH or DOACs) at some point. Some patients had been on both LMWH and DOACs at different time periods. Overall, there were 29 clinically significant bleeding events (including 8 major bleeding) during concurrent treatment and 17 events (4 major bleeding) during factor Xa inhibitor alone over a median follow up of 63 days (52 days for concurrent treatment and 99 days for Xa inhibitor alone). In this self-control study, concurrent treatment was associated with a statistically higher risk of clinically significant bleeding events (HR, 2.84; 95% CI, 1.43-5.64, P < 0.01), which reached 37% patient population in the first 3 months, while the bleeding associated with factor Xa inhibitor alone seemed spaced out at the entire length of anticoagulation (8% by 6 months). Similar trend was found in the analysis of patient group of concurrent TKI and LMWH vs. LMWH alone (HR, 1.96; 95% CI, 0.95-4.02, P = 0.067), although significance was not reached likely due to insufficient power. Sample size was inadequate for meaningful comparison between concurrent VEGFR TKI and DOAC vs. DOAC alone. Conclusions: Concurrent treatment of VEGFR TKI and factor Xa inhibitors is associated with a significantly increased bleeding risks when compared with factor Xa inhibitors alone in patients with metastatic cancer. Disclosures No relevant conflicts of interest to declare.

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Patient and Therapist In-Session Cortisol as Predictor of Post-Session Patient Reported Affect

Brain Sciences ◽

10.3390/brainsci11111483 ◽

2021 ◽

Vol 11 (11) ◽

pp. 1483

Author(s):

Eyal Levi ◽

Susanne Fischer ◽

Hadar Fisher ◽

Roee Admon ◽

Sigal Zilcha-Mano

Keyword(s):

Positive Affect ◽

Stress Hormone ◽

Major Depressive ◽

Retrospective Reports ◽

The Social ◽

Patient Reported ◽

Before And After ◽

The Common ◽

Underlying Mechanisms

The importance of the role of affect in psychotherapy for major depressive disorder (MDD) is well established, but the common use of self-reported measures may limit our understanding of its underlying mechanisms. A promising predictor of patient affect is the stress hormone cortisol. To date, no studies have studied in-session changes in cortisol in psychotherapy for MDD. We investigated whether an increase in patient cortisol over the course of a session correlated with higher negative and lower positive affect. Given previous findings on healthy individuals on the contagious nature of stress, an additional aim was to examine whether these relationships are moderated by therapist cortisol. To this end, 40 dyads (including 6 therapists) provided saliva samples before and after four pre-specified sessions (616 samples). After each session, the patients provided retrospective reports of in-session affect. We found no association between patient cortisol and affect. However, increases in patient cortisol predicted negative affect when the therapists exhibited decreases in cortisol, and increases in patient cortisol predicted positive affect when the therapists showed increases. Our study provides initial evidence for the importance of the social context in the cortisol–affect relationship in MDD.

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Perubahan Status Koagulasi Pasien Kanker Padat Pasca Kemoterapi di Indonesia: Sebuah Studi Prospektif

Jurnal Penyakit Dalam Indonesia ◽

10.7454/jpdi.v7i1.387 ◽

2020 ◽

Vol 7 (1) ◽

pp. 2

Author(s):

Noorwati Sutandyo ◽

Lyana Setiawan

Keyword(s):

Cancer Patients ◽

Prospective Cohort ◽

Stage Iv ◽

Stage Iii ◽

Solid Cancer ◽

Significant Difference ◽

Before And After ◽

Coagulation Status ◽

Stage Iv Cancer ◽

D Dimer

Pendahuluan. Hiperkoagulasi merupakan faktor yang mendasari tingginya mortalitas akibat kejadian tromboemboli vena pada pasien kanker. Kemoterapi merupakan salah satu faktor yang diduga berkontribusi terhadap status hiperkoagulasi pada pasien kanker. Studi ini bertujuan untuk mengevaluasi perubahan status koagulasi yang ditandai dengan kadar D-dimer pada pasien kanker yang menjalani kemoterapi.Metode. Studi ini merupakan studi kohort prospektif di Pusat Kanker Nasional Indonesia yang melibatkan pasien kanker yang sudah terkonfirmasi melalui pemeriksaan histopatologi, dan memulai kemoterapi pada periode Mei hingga Juli 2018. Perubahan status koagulasi dinilai melalui kadar D-dimer plasma. Kadar D-dimer diukur sebelum dan 7 hari setelah kemoterapi. Analisis statistik menggunakan uji t berpasangan untuk menilai kemaknaan perubahan kadar D-dimer plasma sebelum dan setelah kemoterapi.Hasil. Sejumlah 89 pasien memenuhi kriteria inklusi, yang mana 74,2% adalah perempuan dan hampir separuh dari keseluruhan subjek terdiagnosis kanker payudara (44,9%). Mayoritas subjek (69,6%) terdiagnosis pada stadium III atau IV. Sejumlah 12,4% dari subjek mendapatkan kemoterapi berbasis cisplatin. Terdapat perbedaan yang bermakna antara kadar D-dimer sebelum dan setelah kemoterapi (p = 0,05). Studi ini juga menemukan perbedaan bermakna kadar D-dimer sebelum dan sesudah kemoterapi pada pasien kanker stadium III (t(35) = 2,48, p = 0,02) dan stadium IV (t(25) = 2,14, p = 0,04). Tidak terdapat perbedaan bermakna antara kadar D-dimer sebelum dan setelah kemoterapi pada pasien stadium I dan II. Analisis lanjutan berdasarkan kelompok kemoterapi menunjukkan bahwa terdapat perubahan kadar D-dimer yang bermakna pada kelompok yang mendapatkan kemoterapi cisplatin (t(10) = 2,31, p = 0,04), namun tidak pada kelompok yang mendapat kemoterapi non-cisplatin (t(77) = 1,50, p = 0,14).Simpulan. Terdapat perbedaan bermakna status koagulasi yang ditandai dengan kadar D-dimer 7 hari pasca mendapatkan kemoterapi, khususnya pada pasien kanker stadium III atau IV dan mendapatkan kemoterapi berbasis cisplatin. Kata Kunci: Cisplatin, kanker, kemoterapi, status koagulasiChange of Coagulation Status in Solid Cancer Patients Undergoing Chemotherapy in Indonesia: A Prospective Cohort StudyIntroduction. Cancer-associated hypercoagulability was an underlying factor of high mortality of cancer due to venous thromboembolism. Chemotherapy is proposed as one of the contributing factors of the hypercoagulable state. We aim to evaluate the change of coagulation status, which was marked by D-dimer level, in cancer patients receiving chemotherapy.Methods. This is a prospective cohort study in Indonesian national cancer center which involves all adult histologically-confirmed-cancer patients who started chemotherapy between May and July 2018. The coagulation status is assessed by plasma of D-dimer level. We measured D-dimer before chemotherapy and one week after chemotherapy. Paired t-test was performed to assess the significant difference in D-dimer levels before and after chemotherapy.Results. A total of 89 patients fulfilled the eligibility criteria, of whom 74.2% were female and almost half of total subjects (44.9%) were breast cancer patients. Majority of subjects (69.6%) were stage III or stage IV cancer. There were 12.4% of subjects received cisplatin-based chemotherapy. There was a marginally significant difference in plasma level of D-dimers before and after chemotherapy (p = 0.05). We also found significant differences between D-dimer level before and after chemotherapy in stage III patients (t(35) = 2.48, p = 0.02) and stage IV patients (t(25) = 2.14, p = 0.04). There was no significant difference between D-dimer level before and after chemotherapy in stage I and stage II patients. Subgroup analyses based on chemotherapy agents showed that there was significant D-dimer change in cisplatin-based chemotherapy subjects (t(10) = 2.31, p = 0.04), but not in non-cisplatin-based chemotherapy subjects (t(77) = 1,50, p = 0.14).Conclusion. Compared to before chemotherapy, there is a significant difference of coagulation status marked by plasma D-dimer level one week after chemotherapy, particularly in patients with stage III or stage IV cancer and in patients receiving cisplatin-based chemotherapy.

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Use of Anti-angiogenic Drugs Potentially Associated With an Increase on Serum AST, LDH, CK, and CK-MB Activities in Patients With Cancer: A Retrospective Study

Frontiers in Cardiovascular Medicine ◽

10.3389/fcvm.2021.755191 ◽

2021 ◽

Vol 8 ◽

Author(s):

Qi Zheng ◽

Hanzhou Wang ◽

Wei Hou ◽

Ying Zhang

Keyword(s):

Creatine Kinase ◽

Cancer Patients ◽

Muscle Injury ◽

Lactic Dehydrogenase ◽

Cardiovascular Risks ◽

Patients With Cancer ◽

Specific Effects ◽

Before And After ◽

Cancer Types ◽

Myocardial Muscle

Background: There is a large amount of evidence that anti-angiogenic drugs are effective safe. However, few studies have evaluated the specific effects of anti-angiogenic drugs on myocardial enzyme injury biomarkers: aspartate aminotransferase (AST), lactic dehydrogenase (LDH), creatine kinase (CK) and creatine kinase isoenzyme (CK-MB). The purpose of our study was to determine whether anti-angiogenic drugs serum AST, LDH, CK, and CK-MB activities of cancer patients treated with anti-angiogenic drugs.Methods: This study retrospectively analyzed 81 cancer patients. Patients who had used anti-angiogenic drugs were selected. Serum AST, LDH, CK, and CK-MB activities were measured before and after treatment with anti-angiogenic drugs for 3 weeks.Results: A total of 16 cancer types were analyzed. The distribution of the cancer types in the patients was mainly concentrated in lung, gastric, and colorectal cancers. The anti-angiogenic treatment markedly increased AST, LDH, CK, and CK-MB activities by 32.51, 7.29, 31.25, and 55.56%, respectively in serum.Conclusions: Our findings suggest that patients, who had used anti-angiogenic drugs were likely to have elevated AST, LDH, and CK, indicators of myocardial muscle injury. Use of anti-angiogenic drugs should not be assumed to be completely safe and without any cardiovascular risks.

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