Clinical Health Updates

Idraparinux effective for DVT but not for PE

Clinical Question:
Is idraparinux safe and effective for the treatment of acute venous thromboembolism?

Bottom Line:
In patients with deep venous thrombosis, once-weekly subcutaneous idraparinux for 3 or 6 months had an efficacy similar to that of heparin plus a vitamin K antagonist. However, in patients with pulmonary embolism, idraparinux was less efficacious than standard therapy.

Reference:
The van Gogh Investigators, Buller HR, Cohen AT, et al. Idraparinux versus standard therapy for venous thromboembolic disease. N Engl J Med 2007;357(11):1094-1104.

Study Design:
Randomized controlled trial (nonblinded)

Synopsis:
Venous thromboembolism is treated with unfractionated heparin or low-molecular-weight heparin, followed by a vitamin K antagonist. The authors investigated the potential use of idraparinux, a long-acting inhibitor of activated factor X, as a substitute for standard therapy. They conducted two randomized, open-label noninferiority trials involving 2904 patients with deep-vein thrombosis and 2215 patients with pulmonary embolism to compare the efficacy and safety of idraparinux versus standard therapy. Patients received either subcutaneous idraparinux (2.5 mg once weekly) or a heparin followed by an adjusted-dose vitamin K antagonist for either 3 or 6 months. The primary efficacy outcome was the 3-month incidence of symptomatic recurrent venous thromboembolism (nonfatal or fatal). In the study of patients with deep venous thrombosis, the incidence of recurrence at day 92 was 2.9% in the idraparinux group as compared with 3.0% in the standard-therapy group (odds ratio, 0.98; 95% confidence interval [CI], 0.63 to 1.50), a result that satisfied the prespecified noninferiority requirement. At 6 months, the hazard ratio for idraparinux was 1.01. The rates of clinically relevant bleeding at day 92 were 4.5% in the idraparinux group and 7.0% in the standard-therapy group (P=0.004). At 6 months, bleeding rates were similar. In the study of patients with pulmonary embolism, the incidence of recurrence at day 92 was 3.4% in the idraparinux group and 1.6% in the standard-therapy group (odds ratio, 2.14; 95% CI, 1.21 to 3.78), a finding that did not meet the noninferiority requirement.

Epoetin alfa does not reduce transfusions in critically ill

Clinical Question:
Does epoetin alfa reduce the need for transfusions and improve clinical outcomes in critically ill patients?

Bottom Line:
Epoetin alfa did not reduce the need for transfusions in critically ill patients, but increased thrombotic events. Mortality was reduced among the trauma patients.

Reference:
Corwin HL, Gettinger A, Fabian TC, et al, for the EPO Critical Care Trials Group. Efficacy and safety of epoetin alfa in critically ill patients. N Engl J Med 2007;357(10):965-976.

Study Design:
Randomized controlled trial (double-blinded)

Synopsis:
Anemia, which is common in the critically ill, is often treated with red-cell transfusions, which are associated with poor clinical outcomes. The investigators hypothesized that therapy with recombinant human erythropoietin (epoetin alfa) might reduce the need for red-cell transfusions. In this prospective, randomized, placebo-controlled trial, they enrolled 1460 medical, surgical, or trauma patients between 48 and 96 hours after admission to the intensive care unit. Epoetin alfa (40,000 U) or placebo was administered weekly, for a maximum of 3 weeks; patients were followed for 140 days. The primary end point was the percentage of patients who received a red-cell transfusion. Secondary end points were the number of red-cell units transfused, mortality, and the change in hemoglobin concentration from baseline. As compared with the use of placebo, epoetin alfa therapy did not result in a decrease in either the number of patients who received a red-cell transfusion (relative risk for the epoetin alfa group vs. the placebo group, 0.95; 95% confidence interval [CI], 0.85 to 1.06) or the mean (+/-SD) number of red-cell units transfused (4.5+/-4.6 units in the epoetin alfa group and 4.3+/-4.8 units in the placebo group, P=0.42). However, the hemoglobin concentration at day 29 increased more in the epoetin alfa group than in the placebo group (1.6+/-2.0 g per deciliter vs. 1.2+/-1.8 g per deciliter, P<0.001). Mortality tended to be lower at day 29 among patients receiving epoetin alfa (adjusted hazard ratio, 0.79; 95% CI, 0.56 to 1.10); this effect was also seen in prespecified analyses in those with a diagnosis of trauma (adjusted hazard ratio, 0.37; 95% CI, 0.19 to 0.72). A similar pattern was seen at day 140 (adjusted hazard ratio, 0.86; 95% CI, 0.65 to 1.13), particularly in those with trauma (adjusted hazard ratio, 0.40; 95% CI, 0.23 to 0.69). As compared with placebo, epoetin alfa was associated with a significant increase in the incidence of thrombotic events (hazard ratio, 1.41; 95% CI, 1.06 to 1.86).

Cognitive functioning improved by correcting anemia in young women

Clinical Question:
Does treatment improve cognitive abilities in young women with iron deficiency anemia?

Bottom Line:
Women with iron deficiency anemia, on average, perform worse on cognitive tests than women who have sufficient iron stores. Treatment over 4 months improved measures of cognitive performance (accuracy), as well as the speed of performing the tasks.

Reference:
Murray-Kolb LE, Beard JL. Iron treatment normalizes cognitive functioning in young women. Am J Clin Nutr 2007;85:778-787.

Study Design:
Randomized controlled trial (double-blinded)

Synopsis:
Evidence suggests that brain iron deficiency at any time in life may disrupt metabolic processes and subsequently change cognitive and behavioral functioning. Women of reproductive age are among those most vulnerable to iron deficiency and may be at high risk for cognitive alterations due to iron deficiency. The authors examined the relation between iron status and cognitive abilities in young women. A blinded, placebo-controlled, stratified intervention study was conducted in women aged 18-35 y of varied iron status who were randomly assigned to receive iron supplements or a placebo. Cognition was assessed by using 8 cognitive performance tasks (from Detterman’s Cognitive Abilities Test) at baseline (n = 149) and after 16 wk of treatment (n = 113). At baseline, the iron-sufficient women (n = 42) performed better on cognitive tasks (P = 0.011) and completed them faster (P = 0.038) than did the women with iron deficiency anemia (n = 34). Factors representing performance accuracy and the time needed to complete the tasks by the iron-deficient but nonanemic women (n = 73) were intermediate between the 2 extremes of iron status. After treatment, a significant improvement in serum ferritin was associated with a 5-7-fold improvement in cognitive performance, whereas a significant improvement in hemoglobin was related to improved speed in completing the cognitive tasks.

Survivors of childhood acute lymphoblastic leukemia at long-term increased cancer risk

Clinical Question:
Are survivors of childhood acute lymphoblastic leukemia at an increased risk of secondary cancers?

Bottom Line:
The cumulative incidence of secondary neoplasms increases steadily over 30 years after treatment of acute lymphoblastic leukemia. Although the majority of the late-occurring secondary neoplasms are low-grade tumors, the increase in incidence of more aggressive malignant neoplasms is significantly higher than expected in the general population. These results suggest that lifelong follow-up of acute lymphoblastic leukemia survivors is needed to ascertain the full impact of treatment and other leukemia-related factors on secondary neoplasm development.

Reference:
Hijiya N, Hudson MM, Lensing S, et al. Cumulative incidence of secondary neoplasm as a first event after childhood acute lymphoblastic leukemia. JAMA 2007;297:1207-1215.

Study Design:
Cohort (retrospective)

Synopsis:
Little is known about the incidence of secondary neoplasms after 15 to 20 years in children and adolescents who were treated for acute lymphoblastic leukemia. The authors investigated the cumulative incidence of secondary neoplasms in pediatric patients treated for acute lymphoblastic leukemia over 30 years and to characterize late-occurring tumors. Retrospective study of 2169 patients with acute lymphoblastic leukemia treated between 1962 and 1998 at St Jude Children’s Research Hospital, Memphis, Tenn, who achieved complete remission and had a median follow-up time of 18.7 years (range, 2.4-41.3 years). Cumulative incidences of secondary neoplasms in first remission and standard incidence ratios of observed rates compared with rates of cancer development in the general US population. Secondary neoplasms developed as the first event in 123 patients and comprised 46 myeloid malignancies, 3 lymphomas, 14 basal cell carcinomas, 16 other carcinomas, 6 sarcomas, 16 meningiomas, and 22 other brain tumors. The cumulative incidence of secondary neoplasm was 4.17% (SE, 0.46%) at 15 years and increased substantially after 20 years, reaching 10.85% (SE, 1.27%) at 30 years. When meningiomas and basal cell carcinomas were excluded, the overall cumulative incidence was 3.99% (SE, 0.44%) at 15 years and 6.27% (SE, 0.83%) at 30 years, representing a 13.5-fold increase in overall risk compared with the general population. The cumulative incidence of each tumor type at 30 years was 2.19% (SE, 0.32%) for myeloid malignancy, 0.17% (SE, 0.10%) for lymphoma, 3.00% (SE, 0.59%) for brain tumor, 4.91% (SE, 1.04%) for carcinoma, and 0.57% (SE, 0.37%) for sarcoma.

Delayed cord clamping in full-term infants reduces risk of anemia

Clinical Question:
Should we routinely delay umbilical cord clamping in full-term infants for at least 2 minutes?

Bottom Line:
There is no evidence that routinely delaying clamping of the umbilical cord for at least 2 minutes after the birth of full-term infants increases the risk of any significant clinical outcome. Infants with late clamping are at a reduced risk of low ferritin levels and stored iron levels up to 6 months of age. Since there may be some potential long-term risks associated with anemia in the first 6 months of life, strong consideration should be given to routinely delaying the clamping of umbilical cords postdelivery. Additional large randomized trials that include maternal outcomes are needed.

Reference:
Hutton EK, Hassan ES. Late vs early clamping of the umbilical cord in full-term neonates. Systematic review and meta-analysis of controlled trials. JAMA 2007;297:1241-1252.

Study Design:
Meta-analysis (other)

Synopsis:
With few exceptions, the umbilical cord of every newborn is clamped and cut at birth, yet the optimal timing for this intervention remains controversial. The authors compared the potential benefits and harms of late vs early cord clamping in term infants.
Search of 6 electronic databases (on November 15, 2006, starting from the beginning of each):
1. the Cochrane Pregnancy and Childbirth Group trials register
2. the Cochrane Neonatal Group trials register
3. the Cochrane library
4. MEDLINE
5. EMBASE
6. CINHAL
hand search of secondary references in relevant studies; and contact of investigators about relevant published research. Controlled trials comparing late vs early cord clamping following birth in infants born at 37 or more weeks’ gestation. Two reviewers independently assessed eligibility and quality of trials and extracted data for outcomes of interest: infant hematologic status; iron status; and risk of adverse events such as jaundice, polycythemia, and respiratory distress. The meta-analysis included 15 controlled trials (1912 newborns). Late cord clamping was delayed for at least 2 minutes (n = 1001 newborns), while early clamping in most trials (n = 911 newborns) was performed immediately after birth. Benefits over ages 2 to 6 months associated with late cord clamping include improved hematologic status measured as hematocrit (weighted mean difference [WMD], 3.70%; 95% confidence interval [CI], 2.00%-5.40%); iron status as measured by ferritin concentration (WMD, 17.89; 95% CI, 16.58-19.21) and stored iron (WMD, 19.90; 95% CI, 7.67-32.13); and a clinically important reduction in the risk of anemia (relative risk (RR), 0.53; 95% CI, 0.40-0.70). Neonates with late clamping were at increased risk of experiencing asymptomatic polycythemia (7 studies [403 neonates]: RR, 3.82; 95% CI, 1.11-13.21; 2 high-quality studies only [281 infants]: RR, 3.91; 95% CI, 1.00-15.36).