FDA Sounds Alert on Anemia Drugs

Disappearance of Association in Diabetic Patients on Hemodialysis between Anemia and Mortality Risk: The Japan Dialysis Outcomes and Practice Pattern Study

“…Such an analysis was difficult to be performed because of the relatively low hematocrit levels in the patients enrolled in the present study. Only 463 patients (11.7%) of the cohort exceeded a hematocrit of 36% that corresponds to the upper limit of the recommended hemoglobin level (12 g/dl) by the latest FDA Sounds Alert [7] and the KDOQI guidelines [8]. Consideration should be given to the balance required between the benefit of increasing hematocrit levels and the mortality risk.…”

“…Anemia impairs quality of life [1], physical performance [2] and survival [3] in hemodialysis patients, and its partial correction with human recombinant erythropoietin improves physical performance [4] and left ventricular hypertrophy [5]. However, since a recent meta-analysis of these studies showed that full, in contrast with partial, correction of hemoglobin and hematocrit levels is associated with increased risk of all-cause mortality by 17% [6], the US Food and Drug Administration (FDA) advised physicians not to exceed patients’ hemoglobin levels >12 g/dl [7] and The National Kidney Foundation has also updated the target hemoglobin levels generally to be in the range of 11.0–12.0 g/dl in the latest version of the KDOQI guidelines [8]. As one of the mechanisms by which complete normalization of hematocrit levels might increase mortality in hemodialysis patients, we hypothesized, as evidenced from our previous small-scale single-center cohort study, that the presence of atherosclerosis might attenuate the beneficial effect of an increase of hematocrit levels on mortality risk in hemodialysis patients, as evidenced from the disappearance of association between hematocrit levels and mortality in hemodialysis patients with cardiovascular disease (CVD), in which the prevalence of diabetes mellitus (DM) was significantly higher in those with CVD than those without [9].…”

Disappearance of Association in Diabetic Patients on Hemodialysis between Anemia and Mortality Risk: The Japan Dialysis Outcomes and Practice Pattern Study

“…Such an analysis was difficult to be performed because of the relatively low hematocrit levels in the patients enrolled in the present study. Only 463 patients (11.7%) of the cohort exceeded a hematocrit of 36% that corresponds to the upper limit of the recommended hemoglobin level (12 g/dl) by the latest FDA Sounds Alert [7] and the KDOQI guidelines [8]. Consideration should be given to the balance required between the benefit of increasing hematocrit levels and the mortality risk.…”

“…Anemia impairs quality of life [1], physical performance [2] and survival [3] in hemodialysis patients, and its partial correction with human recombinant erythropoietin improves physical performance [4] and left ventricular hypertrophy [5]. However, since a recent meta-analysis of these studies showed that full, in contrast with partial, correction of hemoglobin and hematocrit levels is associated with increased risk of all-cause mortality by 17% [6], the US Food and Drug Administration (FDA) advised physicians not to exceed patients’ hemoglobin levels >12 g/dl [7] and The National Kidney Foundation has also updated the target hemoglobin levels generally to be in the range of 11.0–12.0 g/dl in the latest version of the KDOQI guidelines [8]. As one of the mechanisms by which complete normalization of hematocrit levels might increase mortality in hemodialysis patients, we hypothesized, as evidenced from our previous small-scale single-center cohort study, that the presence of atherosclerosis might attenuate the beneficial effect of an increase of hematocrit levels on mortality risk in hemodialysis patients, as evidenced from the disappearance of association between hematocrit levels and mortality in hemodialysis patients with cardiovascular disease (CVD), in which the prevalence of diabetes mellitus (DM) was significantly higher in those with CVD than those without [9].…”

Effects of Aerobic Exercise Training in Anemic Cancer Patients Receiving Darbepoetin Alfa: A Randomized Controlled Trial

“…Furthermore, the administration of ESAs is now contraindicated in all patients not receiving chemotherapy, because recent studies have shown a negative effect on overall survival in head and neck cancer patients [40], non-small cell lung cancer patients not receiving chemotherapy [7], and cancer patients with active malignant disease not receiving chemotherapy and/or radiation therapy [39]. It is unclear, however, if the adverse effect of ESAs is a result of the higher Hb level itself or if it is a direct effect of the drug on the tumor [41]. If the Hb itself is the cause, then our trial showing that exercise training produces a more rapid Hb response is cause for concern.…”

“…Additionally, 7% of the study participants were not receiving concurrent chemotherapy at the time of initiation of ESA therapy. Such use is now thought to be unsafe outside a clinical trial, given recent safety concerns raised in this population [5,7,41].…”

Disappearance of Association in Diabetic Patients on Hemodialysis between Anemia and Mortality Risk: The Japan Dialysis Outcomes and Practice Pattern Study

“…Such an analysis was difficult to be performed because of the relatively low hematocrit levels in the patients enrolled in the present study. Only 463 patients (11.7%) of the cohort exceeded a hematocrit of 36% that corresponds to the upper limit of the recommended hemoglobin level (12 g/dl) by the latest FDA Sounds Alert [7] and the KDOQI guidelines [8]. Consideration should be given to the balance required between the benefit of increasing hematocrit levels and the mortality risk.…”

“…Anemia impairs quality of life [1], physical performance [2] and survival [3] in hemodialysis patients, and its partial correction with human recombinant erythropoietin improves physical performance [4] and left ventricular hypertrophy [5]. However, since a recent meta-analysis of these studies showed that full, in contrast with partial, correction of hemoglobin and hematocrit levels is associated with increased risk of all-cause mortality by 17% [6], the US Food and Drug Administration (FDA) advised physicians not to exceed patients’ hemoglobin levels >12 g/dl [7] and The National Kidney Foundation has also updated the target hemoglobin levels generally to be in the range of 11.0–12.0 g/dl in the latest version of the KDOQI guidelines [8]. As one of the mechanisms by which complete normalization of hematocrit levels might increase mortality in hemodialysis patients, we hypothesized, as evidenced from our previous small-scale single-center cohort study, that the presence of atherosclerosis might attenuate the beneficial effect of an increase of hematocrit levels on mortality risk in hemodialysis patients, as evidenced from the disappearance of association between hematocrit levels and mortality in hemodialysis patients with cardiovascular disease (CVD), in which the prevalence of diabetes mellitus (DM) was significantly higher in those with CVD than those without [9].…”

Effects of Aerobic Exercise Training in Anemic Cancer Patients Receiving Darbepoetin Alfa: A Randomized Controlled Trial

“…Furthermore, the administration of ESAs is now contraindicated in all patients not receiving chemotherapy, because recent studies have shown a negative effect on overall survival in head and neck cancer patients [40], non-small cell lung cancer patients not receiving chemotherapy [7], and cancer patients with active malignant disease not receiving chemotherapy and/or radiation therapy [39]. It is unclear, however, if the adverse effect of ESAs is a result of the higher Hb level itself or if it is a direct effect of the drug on the tumor [41]. If the Hb itself is the cause, then our trial showing that exercise training produces a more rapid Hb response is cause for concern.…”

“…Additionally, 7% of the study participants were not receiving concurrent chemotherapy at the time of initiation of ESA therapy. Such use is now thought to be unsafe outside a clinical trial, given recent safety concerns raised in this population [5,7,41].…”

Disappearance of Association in Diabetic Patients on Hemodialysis between Anemia and Mortality Risk: The Japan Dialysis Outcomes and Practice Pattern Study

“…Such an analysis was difficult to be performed because of the relatively low hematocrit levels in the patients enrolled in the present study. Only 463 patients (11.7%) of the cohort exceeded a hematocrit of 36% that corresponds to the upper limit of the recommended hemoglobin level (12 g/dl) by the latest FDA Sounds Alert [7] and the KDOQI guidelines [8]. Consideration should be given to the balance required between the benefit of increasing hematocrit levels and the mortality risk.…”

“…Anemia impairs quality of life [1], physical performance [2] and survival [3] in hemodialysis patients, and its partial correction with human recombinant erythropoietin improves physical performance [4] and left ventricular hypertrophy [5]. However, since a recent meta-analysis of these studies showed that full, in contrast with partial, correction of hemoglobin and hematocrit levels is associated with increased risk of all-cause mortality by 17% [6], the US Food and Drug Administration (FDA) advised physicians not to exceed patients’ hemoglobin levels >12 g/dl [7] and The National Kidney Foundation has also updated the target hemoglobin levels generally to be in the range of 11.0–12.0 g/dl in the latest version of the KDOQI guidelines [8]. As one of the mechanisms by which complete normalization of hematocrit levels might increase mortality in hemodialysis patients, we hypothesized, as evidenced from our previous small-scale single-center cohort study, that the presence of atherosclerosis might attenuate the beneficial effect of an increase of hematocrit levels on mortality risk in hemodialysis patients, as evidenced from the disappearance of association between hematocrit levels and mortality in hemodialysis patients with cardiovascular disease (CVD), in which the prevalence of diabetes mellitus (DM) was significantly higher in those with CVD than those without [9].…”

Effects of Aerobic Exercise Training in Anemic Cancer Patients Receiving Darbepoetin Alfa: A Randomized Controlled Trial

“…Furthermore, the administration of ESAs is now contraindicated in all patients not receiving chemotherapy, because recent studies have shown a negative effect on overall survival in head and neck cancer patients [40], non-small cell lung cancer patients not receiving chemotherapy [7], and cancer patients with active malignant disease not receiving chemotherapy and/or radiation therapy [39]. It is unclear, however, if the adverse effect of ESAs is a result of the higher Hb level itself or if it is a direct effect of the drug on the tumor [41]. If the Hb itself is the cause, then our trial showing that exercise training produces a more rapid Hb response is cause for concern.…”

“…Additionally, 7% of the study participants were not receiving concurrent chemotherapy at the time of initiation of ESA therapy. Such use is now thought to be unsafe outside a clinical trial, given recent safety concerns raised in this population [5,7,41].…”