In This Edition
Literature at a Glance
A guide to this month’s studies
- Eplerenone and heart failure mortality
- Fidaxomicin for C. difficile diarrhea
- Guidelines for intensive insulin therapy
- Benefits of hospitalist comanagement
- Peritoneal dialysis versus hemodialysis
- Pneumococcal urinary antigen to guide CAP treatment
- Race and readmission rate
- Factors associated with readmission
- Unplanned transfers to the ICU
Eplerenone Improves Mortality in Patients with Systolic Heart Failure and Mild Symptoms
Clinical question: Does the selective mineralocorticoid antagonist eplerenone improve outcomes in patients with chronic heart failure and mild symptoms?
Background: In prior studies of miner alocorticoid antagonists in systolic heart failure, spironolactone reduced mortality in patients with moderate to severe heart failure symptoms, and eplerenone reduced mortality in patients with acute myocardial infarction complicated by left ventricular dysfunction. The use of eplerenone in patients with systolic heart failure and mild symptoms has not previously been examined.
Study design: Randomized, double-blind, multicenter, placebo-controlled trial.
Setting: Two hundred seventy-eight centers in 29 countries.
Synopsis: The study authors randomized 2,737 patients with New York Heart Association Class II heart failure and an ejection fraction of no more than 35% to either eplerenone (up to 50 mg daily) or placebo, in addition to recommended therapy. Patients with baseline potassium levels >5 mmol/L or estimated GFR <30 were excluded. The primary outcome was a composite of death from cardiovascular causes or hospitalization for heart failure.
The trial was stopped early, after a median follow-up period of 21 months, when an interim analysis showed significant benefit with eplerenone. The primary outcome occurred in 18.3% of patients in the eplerenone group and 25.9% in the placebo group (hazard ratio [HR], 0.63; 95% CI, 0.54 to 0.74; P<0.001). All-cause mortality was 12.5% in the eplerenone group and 15.5% in the placebo group (HR 0.76; 95% CI, 0.62 to 0.93; P=0.008). A serum potassium level exceeding 5.5 mmol/L occurred in 11.8% of patients in the eplerenone group and 7.2% of those in the placebo group (P<0.001).
Bottom line: Eplerenone reduces both the risk of death and the risk of hospitalization in patients with systolic heart failure and mild symptoms.
Citation: Zannad F, McMurray JJ, Krum H, et al. Eplerenone in patients with systolic heart failure and mild symptoms. N Engl J Med. 2011;364(1):11-21.
Fidaxomicin Noninferior to Vancomycin for C. Difficile Treatment
Clinical question: What is the safety and efficacy of fidaxomicin compared to vancomycin in the treatment of patients with C. difficile infection?
Background: Fidaxomicin, a new macrocyclic antibiotic, has shown high efficacy in vitro against C. diff, minimal systemic absorption, and a narrow-spectrum profile. In previously published Phase 2 trials of fidaxomicin for the treatment of C. diff, it has been associated with good clinical response and low recurrence rates.
Study design: Prospective, multicenter, double-blind, randomized trial.
Setting: Fifty-two sites in the United States and 15 in Canada.
Synopsis: The study included 629 adults with acute symptoms of C. diff and a positive stool toxin test. The patients were randomly assigned to 200-mg twice-daily fidaxomicin or 125-mg four-times-daily vancomycin for a course of 10 days. The primary endpoint was rate of clinical cure (resolution of diarrhea), and secondary endpoints were recurrence of C. diff and global cure (clinical cure and lack of relapse within four weeks of cessation of therapy).
The rate of clinical cure associated with fidaxomicin was noninferior to that associated with vancomycin (88.2% vs. 85.8%, respectively). Patients receiving fidaxomicin had a lower rate of relapse than those receiving vancomycin (15.4% vs. 25.3%, respectively, P=0.005) and a higher global cure rate (74.6 vs. 61.1%, P=0.006). In subgroup analysis, the lower rate of recurrence was seen in patients with non-North American pulsed-field Type 1 strain (NAP1/BI/027 strain), while in patients with the NAP1/BI/027 strain, the recurrence rate was similar for both drugs. There was no difference in adverse event rates.