losartan-potassium and Venous-Thromboembolism

Anemia has and will continue to be a central theme in medicine particularly as clinicians are treating a burgeoning population of complex multi-organ system processes. As a result of multiple randomized controlled trials (RCTs), meta-analyses, and societal recommendations overly restrictive paradigms and under-administration of erythropoiesis stimulating agents (ESAs) have likely been followed by clinicians among all specialties.. A review of anemia in the context of chronic kidney disease, hematologic malignancies, and cancer is presented with focus on the establishment of ESAs as integral in the treatment of anemia. Multiple RCTs and meta-analyses studying the use of ESAs are presented with focus upon their application to clinical practice. A 'compendium' is proffered describing the evolution, establishment, and implications of ESA administration initially among those with CKD with rapid subsequent application to the Hematology-Oncology population of patients. Literature search methodologies have included MEDLINE (1985-2020), PubMed (1996-2020), Cochrane Central Trials (1985-2020), EMBASE (2000-2020), and ClinicalTrials.gov (2000-2020).. Upon evaluation of risks and benefits of ESAs focused opinion and commentary is made supporting more liberal use of these agents and strongly suggesting that the current underlying treatment 'pendulum' has perhaps shifted too far to the 'under-treatment' side in many cases.

Topics: Anemia; Blood Transfusion; Combined Modality Therapy; COVID-19; Epoetin Alfa; Erythropoietin; Expert Testimony; Forecasting; Guideline Adherence; Hematinics; Hematologic Neoplasms; Hematopoiesis; Humans; Iron; Medicine; Meta-Analysis as Topic; Multicenter Studies as Topic; Myocardial Ischemia; Neoplasms; Observational Studies as Topic; Pandemics; Practice Guidelines as Topic; Practice Patterns, Physicians'; Randomized Controlled Trials as Topic; Receptors, Erythropoietin; Renal Dialysis; Renal Insufficiency, Chronic; SARS-CoV-2; Venous Thromboembolism

Anemia is common among patients with malignant tumors, due to the disease and chemotherapy. Active oncotherapy, combination chemotherapy of lung cancer is accompanied with many side effects which may impair the patient's quality of life and compromise the effectiveness of chemotherapy, the most frequent one of them being chemotherapy-induced anemia. Anemia decreases not only the patient's quality of life, but also worsens the dose-intensity of chemotherapy. One of the potential treatments of chemotherapy-induced anemia is erythropoietin-stimulating agents (ESAs) for the appropriate indications. Several national and international studies have shown that ESA therapy effectively increases hemoglobin level. However, more recently, contradictory results were published on ESA treatment in terms of survival and tumor progression. The reason for this may be that the tumor cells and endothelial cells may as well express erythropoietin receptor, the role of which has not yet been fully elucidated in tumor progression.. Daganatos betegek körében gyakori szövõdmény az anémia, amelyet maga a betegség vagy az onkológiai kezelés okozhat. A tüdõrák kezelése során az aktív kombinált kemoterápia mellett számos, a beteg életminõségét és az onkoterápia sikerességét rontó mellékhatással kell számolni, ezek közül az egyik leggyakoribb a kemoterápia indukálta anémia. A vérszegénység nemcsak a betegek életminõségét rontja, hanem a citotoxikus kezelés dóziscsökkentéséhez, illetve késleltetéséhez vezethet. A kemoterápia indukálta anémia kezelésének egyik lehetséges útja, az eritropoetin-stimuláló szerek (ESA) használata a megfelelõ indikációval. Számos nemzetközi és hazai tanulmány bizonyította, hogy az ESA-kezelés hatékonyan emeli a hemoglobinszintet. Az utóbbi idõben azonban ellentmondásos eredményeket olvashattunk az ESA-kezelésrõl a túlélés és a daganat progressziója tekintetében. Ennek a hátterében az állhat, hogy a tumorsejtek és az endothelsejtek is kifejezhetnek eritropoetinreceptort, amelynek a szerepe még nem teljesen tisztázott a daganatok progressziójában.

Topics: Anemia; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Carcinoma, Small Cell; Disease Progression; Endothelial Cells; Erythrocyte Transfusion; Erythropoietin; Hematinics; Hemoglobins; Humans; Hypertension; Lung Neoplasms; Quality of Life; Receptors, Erythropoietin; Severity of Illness Index; Venous Thromboembolism

Prior to the approval of the first erythropoiesis-stimulating agent (ESA) in the early 1990s, red blood cell transfusions were the primary means of treating severe chemotherapy-induced anemia (CIA), with little recourse for those with more mild forms of the condition. The introduction of the ESAs allowed treatment of mild-to-moderate CIA in patients with cancer. It has been a decade since darbepoetin alfa (DA), a second-generation ESA with a longer half-life, became available to patients with CIA.. We present a review of studies on DA in CIA, from its development through to the present day. Medline was searched for randomized clinical trials on DA. Additional trials and meta-analyses on ESAs were incorporated into this review when relevant.. The first publications on DA generally focused on optimal dosing, efficacy and tolerability. In these, it was shown that DA is an effective and well tolerated treatment option to achieve hematopoietic response, regardless of dosing interval. Subsequently, the focus shifted towards meta-analyses on survival data of all ESAs. These reported conflicting results regarding mortality and/or disease progression. However, guidelines for ESA use were updated and, when followed, these make ESAs a well tolerated and effective tool for managing CIA.. As the past decade has broadened our knowledge on the benefits and risks of CIA management, continued high-quality studies will help to optimize treatment with ESAs in order to maximize quality of life for these patients. The limitation of a literature review of this nature is the complete reliance on previously published research and the availability of these studies using the methodology outlined above.

Topics: Anemia; Antineoplastic Agents; Blood Transfusion; Darbepoetin alfa; Erythropoietin; Hematinics; Humans; Meta-Analysis as Topic; Neoplasms; Quality of Life; Randomized Controlled Trials as Topic; Venous Thromboembolism

A "biosimilar" or "similar biological medicinal product" is a biological agent that is similar in terms of quality, safety, and efficacy to an authorized reference biological medicine. Since the expiration of the epoetin alfa patent in Europe, three agents have received marketing authorization from the European Medicines Agency: Binocrit (epoetin alfa; aka Abseamed and Epoetin Alfa Hexal), Retacrit (epoetin zeta; aka Silapo), and Eporatio (epoetin theta; aka Biopoin and Ratioepo).. Using the EMA dossiers and journal publications, this article reviews clinical safety data for these products, with emphasis on serious/severe adverse events and a special consideration of immunogenicity, venous thromboembolism, and mortality.. A review of the available safety evidence shows that all three agents discussed have similar safety profiles. None were statistically higher on safety parameters to what is known about ESA as a class, when stratified by population. As with ESAs in general, immunogenicity, venous thromboembolism, and mortality are all concerns. What is known about ESAs regarding safety can be extended to biosimilar erythropoietins. Since biosimilars are unique, complex biological molecules, safety profiles may evolve from common to differentiated, once long-term product-specific safety data are available. Large-sample, long-term, observational studies of real-world practice will provide the heterogeneity and statistical power to demonstrate product-specific effectiveness and safety profiles. Statistically, out of the commercially available formulations of the three products reviewed, no single product is less or more safe.

Topics: Animals; Biosimilar Pharmaceuticals; Drug Hypersensitivity; Drug Monitoring; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Incidence; Pharmacovigilance; Recombinant Proteins; Venous Thromboembolism

Anemia in cancer patients is common and often associated with decreased survival and quality-of-life scores. The introduction of erythropoiesis-stimulating agents (ESAs) for the treatment of anemia in patients with solid tumors and nonmyeloid malignancies in the 1990s has proved an important alternative to red blood cell transfusions. ESAs have been consistently shown to increase hemoglobin levels and reduce transfusion requirements in anemic cancer patients whilst also being associated with improvements in quality of life. Several recent studies, however, have raised concerns about the safety of ESAs with regards to an increased number of thrombo-embolic events, decreased on-study survival and possible effects of ESAs on tumor progression. This has led to a reappraisal of the role of ESAs in the treatment of anemic cancer patients. It remains generally accepted that, if used within current guidelines and labeling recommendations, ESAs can still be considered safe in patients receiving chemotherapy once individual risks are balanced against possible benefits.

Topics: Anemia; Disease Progression; Erythropoietin; Hematinics; Humans; Iron; Neoplasms; Prognosis; Quality of Life; Recombinant Proteins; Venous Thromboembolism

Topics: Adrenal Cortex Hormones; Angiogenesis Inhibitors; Antineoplastic Agents; Antineoplastic Agents, Hormonal; Breast Neoplasms; Clinical Trials as Topic; Erythropoietin; Female; Humans; Models, Biological; Multiple Myeloma; Myeloproliferative Disorders; Neoplasms; Recombinant Proteins; Risk; Thrombophilia; Thrombosis; Venous Thromboembolism

Erythropoiesis-stimulating agents reduce the transfusion requirements of anemic cancer patients receiving chemotherapy. Risks associated with the use of erythropoiesis-stimulating agents in cancer patients have more recently been identified.. Several recently published phase III trials and a meta-analysis have shown an increased risk of venous thromboembolism and a decreased survival in anemic cancer patients treated with erythropoiesis-stimulating agents.. To minimize risks associated with erythropoiesis-stimulating agent use in cancer patients, the most recent American Society of Clinical Oncology/American Society of Hematology clinical practice guidelines and Food and Drug Administration recommendations should be followed.

Topics: Anemia; Antineoplastic Agents; Blood Transfusion; Clinical Trials as Topic; Erythropoietin; Humans; Iron; Neoplasms; Quality of Life; Risk; Signal Transduction; Treatment Outcome; United States; United States Food and Drug Administration; Venous Thromboembolism

The erythropoiesis-stimulating agents (ESAs) erythropoietin and darbepoetin are licensed to treat chemotherapy-associated anemia in patients with nonmyeloid malignancies. Although systematic overviews of trials have identified venous thromboembolism (VTE) risks, none have identified mortality risks with ESAs.. To evaluate VTE and mortality rates associated with ESA administration for the treatment of anemia among patients with cancer.. A published overview from the Cochrane Collaboration (search dates: January 1, 1985-April 1, 2005) and MEDLINE and EMBASE databases (key words: clinical trial, erythropoietin, darbepoetin, and oncology), the public Web site of the US Food and Drug Administration and ESA manufacturers, and safety advisories (search dates: April 1, 2005-January 17, 2008).. Phase 3 trials comparing ESAs with placebo or standard of care for the treatment of anemia among patients with cancer.. Mortality rates, VTE rates, and 95% confidence intervals (CIs) were extracted by 3 reviewers from 51 clinical trials with 13 611 patients that included survival information and 38 clinical trials with 8172 patients that included information on VTE.. Patients with cancer who received ESAs had increased VTE risks (334 VTE events among 4610 patients treated with ESA vs 173 VTE events among 3562 control patients; 7.5% vs 4.9%; relative risk, 1.57; 95% CI, 1.31-1.87) and increased mortality risks (hazard ratio, 1.10; 95% CI, 1.01-1.20).. Erythropoiesis-stimulating agent administration to patients with cancer is associated with increased risks of VTE and mortality. Our findings, in conjunction with basic science studies on erythropoietin and erythropoietin receptors in solid cancers, raise concern about the safety of ESA administration to patients with cancer.

Topics: Anemia; Clinical Trials, Phase III as Topic; Darbepoetin alfa; Erythropoietin; Hematinics; Humans; Neoplasms; Recombinant Proteins; Risk; Survival Rate; Venous Thromboembolism

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Anemia; Castration; Double-Blind Method; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Male; Middle Aged; Prostatic Neoplasms; Quality of Life; Recombinant Proteins; Venous Thromboembolism

The study mainly aimed at investigating possible correlations between peripheral blood counts, erythropoietin (EPO), JAK2 V617F mutation, and vascular complications prior to diagnosis of a population-based cohort of newly diagnosed patients with myeloproliferative neoplasms (MPN).. The study comprises 1105 patients with polycythemia vera (PV) and 1284 patients with essential thrombocythemia (ET) registered in the Swedish MPN Registry.. We conclude that vascular complications among newly diagnosed patients had affected more than one-third of our study population. Risk factors for vascular complications prior to diagnosis were lower hemoglobin in PV, and the presence of JAK2 V617F mutation, higher age, and leukocytosis in ET.

Topics: Age Factors; Aged; Aged, 80 and over; Biomarkers, Tumor; Erythropoietin; Female; Hemoglobins; Humans; Janus Kinase 2; Leukocytosis; Male; Middle Aged; Mutation; Polycythemia Vera; Prospective Studies; Registries; Risk Factors; Sweden; Thrombocythemia, Essential; Venous Thromboembolism

Anaemia is common in cancer patients, with treatments including epoetins and blood transfusions. Although an increased risk of venous thromboembolism (VTE) has been associated with both therapeutics, studies comparing the risk of VTE between epoetins and transfusions in cancer patients are lacking.. A nested case-control study investigated this risk using the German Pharmacoepidemiological Research Database. Cohort members were incident cancer patients receiving first time treatment with epoetin or transfusion. A subcohort including only patients receiving chemotherapy was created, since the formally approved indication of epoetins is chemotherapy-induced anaemia. Cases were defined as patients developing VTE. For each case up to 10 gender- and age-matched controls were selected from the cohort. Multiple confounder adjusted odds ratios (aORs) with 95% confidence intervals (CIs) for VTE and recent treatment with epoetins or transfusions (last 28 days before index date) compared with past anti-anaemic treatment were calculated by conditional logistic regression.. Among 69 888 patients receiving first time treatment with epoetin or transfusion, 3316 VTE cases were identified. The aOR for VTE was 1.31 (95% CI 1.03, 1.65) for epoetins, 2.33 (95% CI 2.03, 2.66) for transfusions, and 2.24 (95% CI 1.34, 3.77) for epoetins and transfusions. Sensitivity analyses with a stricter VTE definition or an expanded time window yielded similar results. In the chemotherapy only subcohort the risk difference between epoetins and transfusions could not be verified (aOR 1.48, 95% CI 1.10, 1.98 vs. aOR 1.80, 95% CI 1.49, 2.19). Our study confirmed known VTE risk factors including previous VTE (aOR 14.76, 95% CI 12.79, 17.03) or surgery (aOR 1.83, 95% CI 1.67, 2.01). Epoetin-associated risk decreased after a safety warning by the European Medicines Agency setting maximum haemoglobin target values to 12 g dl(-1) .. Transfusions could be associated with a higher VTE risk than epoetins in cancer patients. Moreover, current prescribing patterns may have decreased the VTE risk for epoetins.

Topics: Aged; Case-Control Studies; Combined Modality Therapy; Erythropoietin; Female; Humans; Male; Neoplasms; Risk Factors; Transfusion Reaction; Venous Thromboembolism

Venous thromboembolism (VTE) is a significant but poorly understood complication in patients with newly diagnosed multiple myeloma (NDMM). As a result, most patients receive thromboprophylaxis with low molecular weight heparin (LMWH). The purpose of this retrospective study was to identify risk factors for VTE in NDMM and evaluate the effectiveness of LMWH.. A total of 604 patients with newly diagnosed myeloma completed 3 induction cycles with multiagent chemotherapy with up-front randomization to thalidomide between 1998 and 2004. Prophylactic enoxaparin was given to thalidomide recipients beginning in June 2001, and 122 subjects received prophylactic epoetin alfa (EPO) as part of an exercise trial. The primary study endpoint was grades 3-4 VTE.. A total of 72 patients (11.9%) developed VTE (mostly deep venous thrombosis), with a higher incidence among EPO recipients (P = .001), although only significant for upper extremity DVT (P = .0002). The EPO-treated patients had higher hemoglobin (Hb) levels throughout the study (P < .0005), although no relationship between higher Hb levels and increasing incidence of VTE could be shown. A history of VTE was a strong predictor of VTE on univariate analysis (P < .000005). Enoxaparin did not reduce the rate of VTE (P = .158). Logistic regression analysis identified thalidomide therapy (P = .001; odds ratio [OR], 2.428; 95% confidence interval [CI], 1.418-4.159) and prophylactic EPO (P = .002; OR, 2.488; 95% CI, 1.432-4.324) as risk factors for VTE. Myeloma response and survival were not negatively affected by prophylactic EPO or VTE.. Prophylactic EPO, thalidomide therapy, and VTE history, but not higher Hb levels, were found to increase the risk of VTE among NDMM patients receiving multiagent chemotherapy. This risk was not found to be reduced in this population by LMWH thromboprophylaxis.

Topics: Adult; Aged; Anticoagulants; Enoxaparin; Epoetin Alfa; Erythropoietin; Female; Humans; Male; Middle Aged; Multiple Myeloma; Recombinant Proteins; Risk Factors; Thalidomide; Venous Thromboembolism

ESA therapy can increase hemoglobin, decrease blood transfusions, and improve quality of life in patients with chemotherapy induced anemia (CIA). Despite its benefits, ESA therapy increases the risk of venous thromboembolism (VTE) in cancer patients by 50% and can also cause iron restricted erythropoiesis in CIA patients, which may augment the tendency to develop VTE. We postulated that thrombocytosis, a risk factor for VTE in cancer patients, in CIA patients on ESA therapy might be a result of ESA induced iron restricted erythropoiesis. We performed a retrospective analysis of 187 CIA patients who were randomized to receive weekly Epoetin and IV ferric gluconate, oral ferrous sulfate, or no iron for 8 weeks. Nineteen patients experienced 29 VTEs, and patients, whose platelets increased to ≥350,000 cells/uL were three times more likely to experience a VTE (OR 2.9, P = 0.036, logistic regression) with a four times greater incidence of VTE (IRR 4.4, P = 0.001, Poisson regression). Patients treated with IV iron were significantly less likely to develop platelets of ≥350,000 cells/uL (IRR 0.7, P = 0.013, Poisson regression) and had a decreased incidence of VTE. Our study suggests that ESA associated VTE in CIA patients may be, in part, related to the thrombocytosis of ESA induced iron restricted erythropoiesis and may be countered by IV iron.

Topics: Aged; Anemia; Anemia, Iron-Deficiency; Antineoplastic Agents; Double-Blind Method; Epoetin Alfa; Erythropoiesis; Erythropoietin; Female; Ferric Compounds; Ferrous Compounds; Hematinics; Hemoglobins; Humans; Iron; Male; Meta-Analysis as Topic; Middle Aged; Multicenter Studies as Topic; Neoplasms; Randomized Controlled Trials as Topic; Recombinant Proteins; Retrospective Studies; Thrombocytosis; Thrombophilia; Venous Thromboembolism

Risk factors for cancer-associated VTE include certain cancer types (e.g. pancreatic adenocarcinoma), chemotherapy, and the use of erythropoiesis-stimulating agents, central venous catheters, and surgery. We studied the risk factors for cancer-associated VTE in our institution.. Retrospective analysis of patients with solid cancers treated with chemotherapy at King Khalid University Hospital from 2000 to 2010.. We assessed risk factors responsible for VTE, including performance status, age, chemotherapy, use of erythropoietin (EPO), stage of disease and use of a central venous catheter. Patients with other co-morbidities such as diabetes were excluded.. Forty of 306 patients were identified as having VTE, including 111 males and 195 females with a median age of 38 years (range, 13-18 years). Thirty-nine patients had proximal deep vein thrombosis (DVT) and, 4 had pulmonary embolism with no evidence of DVT. Of the 43 patients, 40 patients had stage III or IV at the time of VTE. Thirty patients were taking erythropoietin (40 000 units/ week); 25 had a hemoglobin level higher than 12 g/L. All patients were treated with low molecular weight (LMW) heparin and maintained on LMW heparin or warfarin for minimum of 6 months.. VTE imposes a great risk to life in cancer patients. Risk factors include age more than 40 years, advanced cancer stage, chemotherapy, use of EPO for anemia and underuse of DVT prophylaxis.

Topics: Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Anemia; Anticoagulants; Catheterization, Central Venous; Erythropoietin; Female; Hemoglobins; Heparin, Low-Molecular-Weight; Humans; Male; Middle Aged; Neoplasm Staging; Pancreatic Neoplasms; Retrospective Studies; Risk Factors; Venous Thromboembolism; Warfarin; Young Adult

Erythropoiesis-stimulating agents (erythropoietin and darbepoietin) have been approved to reduce the number of blood transfusions required during chemotherapy; however, concerns about the risks of venous thromboembolism and mortality exist.. We identified patients who were aged 65 years or older in the Surveillance, Epidemiology, and End Results-Medicare database; who were diagnosed with colon, non-small cell lung, or breast cancer or with diffuse large B-cell lymphoma from January 1, 1991, through December 31, 2002; and who received chemotherapy. The main outcome measures were claims for use of an erythropoiesis-stimulating agent, blood transfusion, venous thromboembolism (ie, deep vein thrombosis or pulmonary embolism), and overall survival. We used multivariable logistic regression models to analyze the association of erythropoiesis-stimulating agent use with clinical and demographic variables. We used time-dependent Cox proportional hazards models to analyze the association of time to receipt of first erythropoiesis-stimulating agent with venous thromboembolism and overall survival. All statistical tests were two-sided.. Among 56,210 patients treated with chemotherapy from 1991 through 2002, 15,346 (27%) received an erythropoiesis-stimulating agent. The proportion of patients receiving erythropoiesis-stimulating agents increased from 4.8% in 1991 to 45.9% in 2002 (P < .001). Use was associated with more recent diagnosis, younger age, urban residence, comorbidities, receipt of radiation therapy, female sex, and metastatic or recurrent cancer. The rate of blood transfusion per year during 1991-2002 remained constant at 22%. Venous thromboembolism developed in 1796 (14.3%) of the 12,522 patients who received erythropoiesis-stimulating agent and 3400 (9.8%) of the 34,820 patients who did not (hazard ratio = 1.93, 95% confidence interval = 1.79 to 2.07). Overall survival was similar in both groups.. Use of erythropoiesis-stimulating agent increased rapidly after its approval in 1991, but the blood transfusion rate did not change. Use of erythropoiesis-stimulating agents was associated with an increased risk of venous thromboembolism but not of mortality.

Topics: Aged; Aged, 80 and over; Analysis of Variance; Anemia; Antineoplastic Agents; Blood Transfusion; Breast Neoplasms; Carcinoma, Non-Small-Cell Lung; Colonic Neoplasms; Confounding Factors, Epidemiologic; Darbepoetin alfa; Erythropoietin; Female; Hematinics; Humans; Lung Neoplasms; Lymphoma, Large B-Cell, Diffuse; Male; Medical Record Linkage; Medicare; Neoplasms; Practice Patterns, Physicians'; Recombinant Proteins; Retrospective Studies; Risk Factors; SEER Program; United States; Venous Thromboembolism

Cancer and venous thromboembolism (VTE), VTE and cancer: there is a close bond between these two diseases. On the one hand, a cancer patient runs a high risk of developing VTE. Certain cancer-specific factors, such as its metastatic nature increase this risk. The means involved in the care of cancer (insertion of a venous catheter, chemotherapy, etc.) also increase the probability of a thromboembolism. On the other hand, VTE, especially if it is idiopathic, may be the harbinger of a neoplasm. The present paper involves the dual nature of this relationship, first dealing with several points specific to the occurrence of VTE in a cancer patient, before dealing with the specific care in a curative and prophylactic situation. VTE is then considered as a clinical manifestation prior to a cancer. Several characteristics evoking an underlying neoplasm are known. However, the benefits of the screening for cancer when confronted with an episode of VTE remains to be debated.

Topics: Antineoplastic Agents; Catheterization, Central Venous; Erythropoietin; Humans; Neoplasms; Prognosis; Risk Factors; Venous Thromboembolism

Topics: Anemia; Darbepoetin alfa; Erythropoietin; Hematinics; Humans; Neoplasms; Recombinant Proteins; Risk; Venous Thromboembolism