Oral Vitamin K Versus Placebo to Correct Excess Anticoagulation in Warfarin Patients
Clinical question: In nonbleeding patients with warfarin-associated coagulopathy, does oral vitamin K reduce bleeding events when compared to placebo?
Background: Warfarin is a common drug for primary and secondary prevention of thromboembolism, but it requires continued monitoring of the international normalized ratio (INR) value. INR values >4.0 are associated with an increase in bleeding complications, with specific concern for intracranial bleeding when INR values exceed 4.5. Small, randomized trials have shown that single, low-dose administration of oral vitamin K effectively reduces the INR in nonbleeding, overanticoagulated patients.
However, these studies have not shown if vitamin K reduces risk for bleeding without increasing the risk for thromboembolism.
Study design: Randomized, placebo-controlled trial.
Setting: Fourteen anticoagulation clinics in Canada, Italy, and the U.S.
Synopsis: Nonbleeding patients with supratherapeutic INR values between 4.5 and 10.0 were randomly assigned to receive 1.25 mg of oral vitamin K or placebo, then evaluated for all forms of bleeding for 90 days. Bleeding events were defined as “major bleeding,” “minor bleeding,” and “trivial bleeding.”
Though patients who received oral vitamin K had a significantly more rapid INR decrease, there were no differences between the two groups with regard to all bleeding events, thromboembolism, or death. The study was underpowered to detect differences in major bleeding.
Bottom line: Low-dose oral vitamin K leads to more rapid correction of the INR in overanticoagulated patients on warfarin therapy, but has little effect on clinical outcomes at 90 days.
Citation: Crowther MA, Ageno W, Garcia D, et al. Oral vitamin K versus placebo to correct excessive anticoagulation in patients receiving warfarin: a randomized trial. Ann Intern Med. 2009;150(5):293-300.
Inappropriate Treatment of Catheter-Associated Asymptomatic Bacteriuria
Clinical question: Are hospitalized patients with urinary catheters inappropriately treated with antibiotics for asymptomatic bacteriuria?
Background: Persons with catheters acquire bacteriuria at the rate of 3% to 10% per day, but in the majority of cases, no symptoms or secondary complications occur. Evidenced-based guidelines state that asymptomatic bacteriuria is not a clinically significant infection, and numerous studies have shown that treatment is unlikely to confer clinical benefit.
Study design: Retrospective cohort study.
Setting: A single-site Veterans Affairs hospital.
Synopsis: Using urine culture results over a three-month period from a single VA medical center, 280 cases were analyzed: 164 catheter-associated asymptomatic bacteriuria and 116 catheter-associated urinary tract infections (UTIs). A UTI was defined as having one or more of these symptoms: fever, urgency, frequency, dysuria, suprapubic tenderness, altered mental status, or hypotension in a patient without another recognized infection and a positive urine culture. Of the asymptomatic bacteriuria cases, 68% were managed appropriately with no antibiotic treatment; 32% were inappropriately treated with antibiotics.
In multivariate analysis, older patient age, predominance of gram-negative bacteria, and higher urine white blood cell count were significantly associated with inappropriate treatment.
This study highlights the fact that antibiotics continue to be used inappropriately in patients with catheters. Current guidelines do not distinguish well between asymptomatic bacteriuria and UTI, so there might be a knowledge gap. This study was based on urine culture data, not urinalysis of all patients with a catheter, so the symptomatic patients were likely over-represented.
An associated editorial observes that the study extrapolates data from studies that involved patients with uncomplicated UTIs and, therefore, might reach erroneous conclusions. Further, viewing catheter-associated symptomatic UTIs and catheter-associated asymptomatic bactiuria as dichotomous and warranting inherently different management fails to encompass a number of clinical factors, including co-infection, and further fails to acknowledge that removal of the catheter is the first step in treatment. However, the finding that antibiotics continue to be used inappropriately is useful.