Abstract
Background: Anemia is a common condition among elderly and its prevalence increases with age. Fatigue is well recognized as a prominent feature of chronic anemia and may be especially symptomatic in this population. In order to evaluate the effect of epoetin alfa (EPO) treatment on hemoglobin (Hb), fatigue, and health related quality of life (QOL) in elderly patients (pts) with chronic anemia a 32 week(w) randomized, double-blind, cross-over treatment trial among community-dwelling participants ≥65y was conducted. Pts were ambulatory and had anemia for ≥3 months with inclusion Hb ≤11.5g/dL. Pts with GI bleeding, active cancer, CKD (GFR<30), thrombocytopenia, iron deficiency, hypothyroidism, untreated depression, dementia, or expected survival ≤6months were excluded. Pts were randomized to receive either subcutaneous (sc) placebo or EPO weekly for 16w (Phase 1) and then crossed over to the other treatment (Phase 2). QOL was measured using the Functional Assessment of Cancer Therapy-Anemia (FACT-An) instrument, with specific focus on the Anemia and Fatigue subscales of the instrument. Hb was measured every 4w. Analyses of all efficacy endpoints were based on pts who had who had at least one Phase 1 (58/62) and one Phase 2 (55/58) visit (using analysis of covariance controlling for baseline values).
Results: 62 pts, 85% women, and 95% African American with a mean (SD) age of 76.1y (±7.2). Mean baseline Hb was 10.5±0.9 g/dL (7.3–11.5); 75% had anemia of chronic disease and 25% had unexplained anemia. Common baseline comorbidities included hypertension, CHF, osteoarthritis, and Type 2 diabetes. Seven pts did not complete the study. There was 1 death, 1 stroke and 1 DVT on placebo and 1 death and 1 pulmonary embolus on EPO. None of the serious adverse events or deaths were considered treatment-related. Pts receiving EPO had significantly increased Hb compared to placebo at the end of phases 1 and 2 (p<0.0001; Table 1) and, significantly improved scores on the composite FACT-An (p<0.0107, phase 1; p=<0.0001, phase 2), FACT-An anemia subscale (p=0.0017, phase 1; p=0.0003, phase 2) and FACT-An fatigue subscale (p=0.0012, phase 1; p=0.0011, phase 2).
Conclusion: A direct relationship exists between increasing Hb during EPO therapy, fatigue scores and corresponding QOL improvements among elderly persons with anemia. EPO was well tolerated in this trial among anemic elderly pts. Improving fatigue may enhance ability to perform daily activities in the elderly.
Phase One - No Epo (n=25) Phase One-EPO(n=30) Variable LS mean Std Err LS Mean Std Err p-value* Difference in LS mean between groups * ANCOVA predicting last phase one study score controlling for baseline Phase 1 score Fatigue Subscale (0–52) 36.3 1.3 42.4 1.2 0.0012 6.1 Anemia Subscale (0–80) 56.1 1.5 63.1 1.4 0.0017 6.9 FACT-An (0–188) 138.0 3.0 148.9 2.8 0.0107 10.9 Hb (g/dl) 10.7 0.2 13.2 0.2 <0.0001 2.4 Phase Two- No EPO (n=30) Phase Two- EPO (n= 25) Variable LS Mean Std Err LS Mean Std Err p-value** Difference in LS mean between groups **ANCOVA predicting last phase two study score controlling for baseline (visit 17) score. Fatigue subscale (0–52) 34.2 1.6 42.8 1.8 0.0011 8.5 Anemia Subscale (0–80) 53.2 1.9 64.5 2.1 0.0003 11.3 FACT-An (0–188) 130.6 3.6 153.4 4.0 <0.0001 22.9 Hb (g/dl) 10.8 0.3 13.3 0.3 <0.0001 2.5
Once-daily eprosartan mesylate in the treatment of elderly patients with isolated systolic hypertension: data from a 13-week double-blind, placebo-controlled, parallel, multicenter study