In the News

Acute venous thromboembolism treatment, flu vaccines, and more.

Apixaban noninferior to conventional therapy for acute VTE, study indicates

Fixed-dose treatment with apixaban was noninferior to conventional therapy for acute venous thromboembolism (VTE) and appeared to be associated with significantly less bleeding, according to a recent industry-funded study.

Researchers performed a randomized, double-blind trial comparing apixaban, 10 mg twice daily for seven days, then 5 mg twice daily for six months, with conventional treatment (i.e., subcutaneous enoxaparin, then warfarin) in a group of patients with acute VTE. From August 2008 through August 2012, patients at 358 centers in 28 countries were included in the study if they were at least 18 years old and had symptomatic proximal deep venous thrombosis or pulmonary embolism that had been objectively confirmed. The study's primary efficacy outcome was recurrent, symptomatic VTE or death related to VTE, and the principal safety outcomes were major bleeding and major bleeding plus clinically relevant nonmajor bleeding. The results of the study, which was funded by Pfizer and Bristol-Myers Squibb, were published in the Aug. 29 New England Journal of Medicine.

A total of 5,395 patients were included in the study, 2,691 assigned to apixaban and 2,704 assigned to conventional treatment. The mean age was approximately 57 years, and a majority of the patients (58.3% in the apixaban group and 59.1% in the conventional treatment group) were men. Fifteen patients in each group did not receive the study therapy. Patients were assessed in the clinic or by phone at 2, 4, 8, 12, 16, 20 and 24 weeks post-randomization as well as 30 days after the intended treatment period ended. Fifty-nine of 2,609 patients in the apixaban group (2.3%) and 71 of 2,635 patients in the conventional treatment group (2.7%) developed the primary efficacy outcome (relative risk, 0.84 [95% CI, 0.60 to 1.18]; difference in risk, 0.4 percentage point [95% CI, −1.3 to 0.4 percentage point]). A total of 0.6% of patients in the apixaban group and 1.8% of those in the conventional treatment group developed major bleeding (relative risk, 0.31 [95% CI, 0.17 to 0.55]; P<0.001 for superiority), and 4.3% and 9.7%, respectively, developed major bleeding plus clinically relevant nonmajor bleeding (relative risk, 0.44 [95% CI, 0.36 to 0.55]; P<0.001). Other adverse events did not differ between groups.

The authors noted that additional studies are needed to determine the safety and efficacy of apixaban in patients with cancer, those with low body weight, and those with a creatinine clearance below 50 mL/min. However, they concluded that based on their results and those of a previous study, “apixaban provided a simple, effective, and safe regimen for the initial and long-term treatment of venous thromboembolism” and was associated with a clinically relevant reduction in major bleeding.

The author of an accompanying editorial noted that many exclusion criteria were used in the current trial and that the results, which were from 28 countries, were not broken down by geographic region. Also, she stressed that of the currently available new anticoagulants, only rivaroxaban is FDA-approved for treatment of acute VTE, and dabigatran is being used off-label. Her institution uses a protocol that includes six key points for using new anticoagulants in acute VTE: patient preference, patient selection, drug interactions, compliance, follow-up and monitoring.

“As we translate knowledge from the era of vitamin K antagonists to new agents, it is critical that we consider the factors discussed here,” the editorialist wrote. “More information is needed on reversal strategies, monitoring (e.g., in the presence of interacting drugs, extremes of patient weight, or bleeding or thrombosis complications), approaches to treatment failure, comparisons of adherence to treatment among new drugs and warfarin, and formal cost-effectiveness analyses. Comparative-effectiveness studies and postmarketing surveillance are key.”

CDC committee recommends specific flu vaccine as an option for people with egg allergy

The immunization advisory committee at the Centers for Disease Control and Prevention (CDC) recently recommended using the vaccine FluBlok in the 2013-14 flu season for people aged 18 through 49 years with egg allergy.

Unlike other available seasonal flu vaccines, FluBlok does not use the influenza virus or chicken eggs in its manufacturing process and can be used in adults with an egg allergy of any severity, the CDC said in a press release. FluBlok was licensed by the Food and Drug Administration (FDA) in January 2013. The most common side effects are pain at the injection site, headache, fatigue, and muscle aches.

FluBlok has a shorter shelf life than other influenza vaccines, so clinicians should be sure to check the expiration date before administering it, the CDC said.

Boxed warning for hydroxyethyl starch solution in critically ill

The FDA has added a boxed warning to hydroxyethyl starch solutions about a higher risk of death and severe renal injury in critically ill patients, the agency said in a recent safety alert.

Hydroxyethyl starch solution (HES) shouldn't be used in patients with sepsis and those admitted to the ICU and should be avoided in those with preexisting renal dysfunction, the FDA said. Also, clinicians should stop treatment at the first sign of renal injury, then monitor renal function for 90 days afterward. HES should be discontinued at the first sign of coagulopathy, as well, the agency said.

HES also should be avoided in patients having open-heart surgery in association with cardiopulmonary bypass, as it poses a risk of excess bleeding, the FDA said.

Low-risk patients may not need vital signs checked so often, study suggests

Clinicians may be able to reduce the frequency of vital sign checks at night for low-risk inpatients without compromising quality of care, a study suggests.

Researchers conducted a prospective cohort study of 54,096 consecutive adult inpatients at a 550-bed academic institution between November 2008 and August 2011. Vital signs were taken from the electronic medical record and a Modified Early Warning Score (MEWS) was calculated. The number of disruptions for vital sign monitoring between 11 p.m. and 6 a.m., and the occurrence of adverse events, defined as intensive care unit transfers or cardiac arrests in the next 24 hours, were compared across all MEWS categories.

The median evening MEWS was 2 (interquartile range, 1 to 2). The adverse event rate increased with higher evening MEWS, from a rate of 5.0 per 1,000 patient-days (when the MEWS was ≥1) to 157.3 per 1,000 patient-days (when the MEWS was ≤7) (P=0.003 for trend). However, the frequency of vital sign disruptions was unchanged, with a median of two vital sign checks per patient per night and at least one disruption from vital sign collection 99.3% of the nights, no matter the MEWS category. Forty-five percent of all nighttime vital sign disruptions occurred in patients with a MEWS of 1 or less. Results were published online July 1 by JAMA Internal Medicine.

The evening MEWS identified a subset of patients at lower risk of adverse events who had their overnight vital signs taken at similar rates as high-risk patients, the authors noted, suggesting the monitoring frequency of low-risk patients could be reduced. “Such a reduction could have dramatic benefits to patient sleep, considering that vital sign checks have been shown to be the environmental factor most disruptive to patient sleep,” the authors wrote. Sleep deprivation is also an important factor in post-hospitalization syndrome, which recent research suggests may increase readmissions, they noted. Reducing vital signs monitoring could reduce nurse staffing needs and save money, and/or enable reallocation of resources to increase monitoring of high-risk patients, they wrote.

Actual observation patients different from CMS’ intentions

Characteristics of observation patients differ from what was likely intended by the Centers for Medicare and Medicaid Services (CMS), and hospitals and patients are getting hit in the wallet as a result, a recent study and editorial suggest.

Researchers at the University of Wisconsin Hospital and Clinics sought to describe inpatient and observation care at their 566-bed medical center between mid-2010 and December 2011. They examined 43,853 stays, looking at patient demographics, length of stay, difference between cost and reimbursement per stay, and percentage of patients discharged to skilled nursing facilities. They noted that CMS defines observation status as “a well-defined set of specific, clinically appropriate services,” usually lasting less than 24 hours, and in only “rare and exceptional cases” lasting more than 48 hours.

About 10% of the total stays (n=4,578) were for observation and comprised 1,141 distinct diagnosis codes. The mean length of stay for those under observation was 33.3 hours. Forty-four percent of observation stays were shorter than 24 hours, and 16.5% were longer than 48 hours. Adult general medicine patients accounted for 52.5% of all observation stays, and about one-quarter of the adult general medicine stays were classified as observation.

The mean length of stay for general medicine observation patients was 41.1 hours, and 32.6% of stays were shorter than 24 hours. Compared to observation patients on other clinical services, adult general medicine had the highest percentage of patients who were discharged to skilled nursing facilities (11.6%), where coverage is only reimbursed by CMS after three days of inpatient stay. Results were published online July 8 by JAMA Internal Medicine.

The wide variety of diagnoses “suggest that observation status is not well defined,” the authors wrote. Also, the length of stay in observation care is often longer than the CMS benchmark of 24 hours, they noted. In particular, adult general medicine patients have longer lengths of stay and are more apt to stay longer than 48 hours in observation (26.4%), compared to other patients. Compared with observation patients on other clinical services, general medicine observation patients are also more likely to be discharged to a skill nursing facility (SNF), have more avoidable days of hospitalization, have more acute/unscheduled admissions, and have more repeat encounters.

“The cost for observation care was less than the cost for inpatient care, but reimbursement was markedly lower, resulting in [hospital] operating losses and the transfer of some costs to patients,” the authors wrote. “Observation care in clinical practice is very different than what CMS initially envisioned and creates insurance loopholes that adversely affect patients, health care providers, and hospitals.”

In an editorial, Robert Wachter, MD, FACP, noted that a new CMS rule should improve the situation by clarifying that patients who stay in the hospital for at least two midnights are considered inpatients and those who stay less than two midnights are observation patients. CMS could improve matters further by requiring hospitals to tell patients of their observation or inpatient status and by allowing hospitals to retroactively change a patient's status based on information that wasn't initially available, he wrote.