Why should this article be of interest to kidney doctors? Two reasons – first: we also look after a relatively older population with cardiac comorbidities and have taken the approach that a Hb of <10 g/dL could be problembatic in these high risk patients, and second – there has been a strong argument that lowering the Hb threshold from 10 g/dL to 9 g/dL would result in an increase in blood transfusions and that this could be harmful.
Strictly speaking, this study should not be generalized to the ESRD even the CKD patient population, because patients with kidney disease are probably sicker and more symptomatic than elderly patients undergoing hip surgery, even though the hip surgery patients enrolled in this trial were quite elderly (mean age approximately 81 years) and selected for a history of or risk of cardiovascular disease (>60%). Still, it might provide some insights into whether the fixation with a Hb 10 g/dL threshold should be re-examined.
The article by Carson and colleagues tests the hypothesis that a higher threshold for blood transfusion (a hemoglobin level of 10 g/dL) improves functional recovery and reduces morbidity and mortality, as compared with a more restrictive transfusion strategy (a hemoglobin level of <8 g/dL or symptoms).
Patients who had a hemoglobin level of <10 g per deciliter within 3 days after hip surgery were randomized to either a liberal or a restrictive blood transfusion strategy.
The study was multicenter, and sponsored by the NIH. Tha sample size was 2016 subjects. The study was not blinded. The study eligibilty criteria were:
Patients who had a hemoglobin level of <10 g per deciliter within 3 days after hip surgery were randomized to either a liberal or a restrictive blood transfusion strategy.
The study was multicenter, and sponsored by the NIH. Tha sample size was 2016 subjects. The study was not blinded. The study eligibilty criteria were:
- age>50 year or older
- undergoing primary surgical repair of a hip fracture
- with clinical evidence of or risk factors for cardiovascular disease
- a history of ischemic heart disease
- electrocardiographic evidence of previous myocardial infarction
- a history or presence of congestive heart failure and/or peripheral vascular disease
- a history of stroke or transient ischemic attack
- had a hemoglobin level of less than 10 g per deciliter within 3 days after surgery
[Approximately 18 months following the start of the study, the eligibility criteria were expanded to enhance recruitment by including patients with any of the following cardiovascular risk factors: a history of or treatment for hypertension, diabetes mellitus, or hypercholesterolemia; a cholesterol level >200 mg/dL or a low-density lipoprotein cholesterol level >130 mg/dL; current tobacco use; or a creatinine level of more than 2.0 mg/dL].
Patients were randomized to either a “liberal-strategy group or the restrictive-strategy group using an automated telephone randomization system by randomly ordered block sizes of two, four, six, or eight.
Patients in the liberal-strategy group received 1 unit of packed red cells and additional blood as needed to maintain a hemoglobin level of >10 g/dL. An assessment of the hemoglobin level after transfusion was required, and an additional unit of blood was transfused if the patient's hemoglobin level was <10 g/dL.
Patients in the restrictive-strategy group were permitted to receive transfusions if symptoms or signs of anemia developed (chest pain, CHF, unexplained tachycardia or hypotension) or at the discretion of their physicians if the hemoglobin level fell <8 g/dL.
The average hemoglobin level before transfusion was 1.3 g per deciliter higher in the liberal-strategy group than in the restrictive-strategy group (P<0.001) The median number of units transfused was 2.0 (interquartile range, 1 to 2) in the liberal-strategy group and 0 (interquartile range, 0 to 1) in the restrictive-strategy group; 59.0% of patients in the restrictive-strategy group did not receive a transfusion after randomization.
The mean age of the study population was 81.6 years (range, 51 to 103), and cardiovascular disease was present in 62.9%. Baseline characteristics were similar in the two study groups
The primary outcome was death or an inability to walk 10 ft (or across a room) without human assistance at the 60-day follow-up.
Secondary outcomes included a combined outcome of in-hospital myocardial infarction, unstable angina, or death for any reason. Other secondary outcomes included current residence, survival, functional measures (lower-extremity physical and instrumental activities of daily living), and fatigue. Tertiary outcomes included in-hospital morbidity up to 30 days after randomization, including pneumonia, wound infection, thromboembolism, stroke or transient ischemic attack, and clinically recognized myocardial infarction.
The study had two prespecified composite outcomes: death, myocardial infarction, or pneumonia; and death, myocardial infarction, pneumonia, thromboembolism, or stroke.
Key results
1. The rates of death or an inability to walk without human assistance at 60-day follow-up were similar in the liberal-strategy group and the restrictive-strategy group (35.2% vs. 34.7%, P=0.90). The odds ratio for the primary outcome associated with the liberal strategy versus the restrictive strategy was 1.01 (95% confidence interval [CI], 0.84 to 1.22), for an absolute risk difference of 0.5 percentage points (95% CI, −3.7 to 4.7).
2. There were no significant between-group differences in the rates of death on 30-day follow-up (5.2% in the liberal-strategy group vs. 4.3% in the restrictive-strategy group), for an absolute risk difference of 0.9 percentage points (99% CI, −1.5 to 3.4), and on 60-day follow-up (7.6% in the liberal-strategy group vs. 6.6% in the restrictive-strategy group), for an absolute risk difference of 1.0 percentage point (99% CI, −1.9 to 4.0).
3. The between-group differences were also not significant in the rates of in-hospital acute myocardial infarction, unstable angina, or death (4.3% in the liberal-strategy group vs. 5.2% in the restrictive-strategy group), for an absolute risk difference of −0.9 percentage points (99% CI, −3.3 to 1.6).
4. The frequencies of in-hospital clinical events and serious adverse events did not differ significantly between groups.
5. The length of hospital stay, scores for lower-extremity physical activities of daily living, instrumental activities of daily living, and fatigue, as well as rates of residing at home at 30-day and 60-day follow-up were also similar.
6. Patients in the restrictive-strategy group received 65% fewer units of blood than those in the liberal-strategy group; more than half the patients in the restrictive-strategy group did not receive any blood transfusion.
Limitations of the Study
This was a well designed and superbly executed study. However, there are some limitations that the authors themselves acknowledge: there were no follow-up examinations, telephone ascertainment of functional outcomes may introduce biases and errors. The investigators did not validate patients' ability to walk, in cases in which both patients. The eligibility criteria were revised during the course of the trial to include lower-risk patients who had cardiovascular risk factors but no history of cardiovascular disease.
Other limitations included the modest difference in Hb levels between the two groups. Because the difference in Hb between the 2 arms of the study was only 1 g/dL (that too at day 7 post-randomization) this may have attenuated any difference in the walking test, i.e., biased towards a null finding. Of note, no Hb levels after 7 days are reported, even though the investigators hypothesized that an increased hemoglobin level would allow patients to participate more actively in rehabilitation and therefore increase the proportion who were walking independently 60 days after randomization. The authors state “the assigned transfusion strategy was to be followed until discharge or up to 30 days, whichever came first”.
The article had an accompanying NEJM editorial by Barr and Bailie that concluded: “the FOCUS trial provides new evidence to support the view that a more restrictive transfusion threshold in the absence of symptoms of anemia may be reasonable, including in elderly patients at risk for cardiovascular events.”
The bottom-line is that a restrictive approach to blood transfusion in anemic but asymptomatic elderly high risk patients with a Hb<10 g/dL is reasonable, despite the limitations of this study.
While this study doesn’t prove that these results should be generalized to ESRD or non-dialysis CKD patients, it raises the possibility that a restrictive approach might also be a reasonable strategy in asymptomatic kidney patients.
Recall that subjects in TREAT (non-dialysis diabetic patients with CKD which had a Hb threshold in the placebo arm of 9 g/dL) and the low Hb arm of the Normal Hematocrit study (symptomatic dialysis patients who had a 9-11 g/dL Hb target in the low Hb arm) did better, or at least not worse, than patients with a higher Hb concentration.
While this study doesn’t prove that these results should be generalized to ESRD or non-dialysis CKD patients, it raises the possibility that a restrictive approach might also be a reasonable strategy in asymptomatic kidney patients.
Recall that subjects in TREAT (non-dialysis diabetic patients with CKD which had a Hb threshold in the placebo arm of 9 g/dL) and the low Hb arm of the Normal Hematocrit study (symptomatic dialysis patients who had a 9-11 g/dL Hb target in the low Hb arm) did better, or at least not worse, than patients with a higher Hb concentration.
This is a vein and vascular center that has multiple locations. They are located in near PHOENIX, ARIZONA, USA. Office locations are, Surprise, Arizona, USA, - Goodyear, Arizona USA, Chandler, Arizona USA and Gilbert , Arizona USA. These cities surround Phoenix, so we want to focus on each city and about a 20 mile radius around each one as well as Phoenix itself since it is in the center of all these cities.
ReplyDelete