Recent Research

Rivaroxaban versus warfarin, postop frailty score, parasitic infections and more.


Rivaroxaban has similar efficacy as warfarin in certain patients

Rivaroxaban appears to have similar safety and efficacy compared with warfarin in both older and younger patients with nonvalvular atrial fibrillation, although stroke and major bleeding rates were higher in the former group, a recent study found.

Researchers from the ROCKET AF trial, which was funded by Johnson & Johnson Pharmaceutical Research & Development and Bayer Healthcare, performed a prespecified secondary analysis to compare outcomes of rivaroxaban and warfarin treatment in older versus younger patients. Patients were included in ROCKET AF if they had nonvalvular atrial fibrillation and previous stroke, transient ischemic attack, or systemic embolism or at least 2 risk factors for stroke. Patients were randomly assigned to receive adjusted-dose warfarin with a target international normalized ratio of 2.0 to 3.0 or rivaroxaban, 20 mg/d (15 mg/d in those with a creatinine clearance <50 mL/min). The primary study end point was stroke and systemic embolism according to intention to treat. The study results were published in the July 8 Circulation.

ROCKET AF included 14,264 patients, 6,229 of whom (44%) were 75 years of age or older. The median age was 79 years in elderly patients and 66 years in younger patients. The study involved a total of 10,866 patient-years of exposure, over which rates of primary events (2.57% vs. 2.05% per 100 patient-years; P=0.0068) and major bleeding (4.63% vs. 2.74% per 100 patient-years; P<0.0001) were higher in older patients than in younger patients. However, for rivaroxaban versus warfarin, rates of stroke and systemic embolism as well as major bleeding were consistent among older and younger patients.

Stroke and systemic embolism occurred among 2.29% of elderly patients taking rivaroxaban and 2.85% of those taking warfarin per 100 patient-years (hazard ratio [HR], 0.80; 95% CI, 0.63 to 1.02), while rates among younger patients were 2.00% versus 2.10% per 100 patient-years (HR, 0.95; 95% CI, 0.76 to 1.19). Major bleeding rates among elderly patients were 4.86% per 100 patient-years in those taking rivaroxaban and 4.40% per 100 patient-years in those taking warfarin (HR, 1.11; 95% CI, 0.92 to 1.34), compared with 2.69% versus 2.79% per 100 patient-years in younger patients (HR, 0.96; 95% CI, 0.78 to 1.19). Rates of hemorrhagic stroke were also similar in both younger and older patients.

The authors noted that ROCKET AF might not have lasted long enough to capture the true rates of potential adverse events and that included patients were all at fairly high risk for stroke, among other limitations. However, they wrote, “The main clinical implication of this study is that in elderly patients with nonvalvular [atrial fibrillation] at high risk of stroke, factor Xa inhibition with rivaroxaban is as effective as adjusted-dose anticoagulation with warfarin.”

An accompanying editorial pointed out that “new oral anticoagulants may offer increased convenience for elderly patients, because of their more predictable pharmacologic profiles, a rapid onset of action, a broader therapeutic window, and no specific requirement for routine coagulation monitoring,” in addition to fewer food and drug reactions than warfarin. The authors suggested that existing bleeding risk scores could be improved in the elderly and noted that warfarin is still the preferred therapy in some patients, such as those with mechanical valves or left ventricular thrombi and those in whom the ability to monitor international normalized ratio is helpful. Warfarin is also less expensive, the authors stressed.

“Regardless of the medication chosen, however, older patients must always be treated cautiously due to an increased risk of stroke and bleeding, and additional challenges related to drug interactions,” the editorialists wrote. “As additional data is gathered in this large and higher risk population, our ability to guide optimal use in terms of risk/benefit as well as choose the optimal medication/dosage and mitigate drug interaction, will expand and lead to better care of our older patients. However, while there is no doubt about the benefits of oral anticoagulation in the elderly, focus must be placed on reducing their risk.”

Frailty score may help predict postop mortality risk in the elderly

A multidimensional frailty score helped predict postoperative mortality risk in elderly patients, according to a recent study.

Researchers at a tertiary care center in Korea studied consecutive patients at least 65 years of age who were having intermediate-risk or high-risk elective surgery. Patients who had emergency surgery or who were classified as low risk for adverse outcomes after surgery according to American College of Cardiology/ American Heart Association 2007 guidelines were excluded. The goal of the study was to develop a model that would predict adverse outcomes in elderly patients undergoing surgery. To that end, all patients received a comprehensive geriatric assessment, which involved burden of comorbidity, polypharmacy, physical function, psychological status, nutrition, and risk for postoperative delirium. Most received the assessment within a month prior to surgery, although 13 received it 1 to 3 months before surgery.

The study's main outcome measure was all-cause mortality at 1 year, while secondary outcomes were postoperative complications (unplanned ICU admissions, pneumonia, urinary tract infection, or acute pulmonary thromboembolism), length of stay, and discharge to a nursing facility if the patient had previously lived at home. The study results were published in the July JAMA Surgery.

From Oct. 19, 2011, to July 31, 2012, 275 patients were included in the study. Mean age was 75.4 years, and 55% were men. Twenty-five patients (9.1%) died during a median follow-up of 13.3 months, 4 in the hospital after their surgery. At least 1 postsurgery complication occurred in 29 patients (10.5%), and 24 patients (8.7%) were discharged to nursing facilities. Patients who died were more likely to have malignant disease and low levels of serum albumin than those who did not. Higher mortality rates were associated with Charlson Comorbidity Index scores, dependence in activities of daily living and instrumental activities of daily living, dementia, delirium risk, short midarm circumference, and malnutrition.

The researchers developed a frailty score based on these factors and found that it performed better when predicting rates of all-cause mortality than the American Society of Anesthesiologists score (area under the receiver-operating characteristic curve, 0.821 vs. 0.647; P=0.01). Based on the frailty score, patients were divided into those with a score greater than 5 and those with a score of 5 or lower, with a higher score indicating higher risk. Sensitivity was 84.0% and specificity was 69.2% for all-cause mortality. Patients with high-risk frailty scores had higher risk for death (hazard ratio, 9.01; P=0.003) and longer hospital stays (median, 9 vs. 6 days; P<0.001) after surgery.

The researchers noted that their study involved a single hospital and that the results therefore might not be generalizable to other settings. In addition, they pointed out that their model did not show statistical significance when predicting outcomes after surgery. However, they concluded that their score, which is based on a comprehensive geriatric assessment, is better than other conventional methods when predicting 1-year all-cause mortality rate after surgery, length of hospital stay, and risk for discharge to a nursing facility.

“This model may support surgical treatments for fit older patients at low risk of complications, and it may also provide an impetus for better management of geriatric patients with a high risk of adverse outcomes after surgery,” the researchers concluded.

Early epinephrine in cardiac arrest with non-shockable rhythm associated with better survival

Earlier administration of epinephrine for inpatients with cardiac arrest increases the chances that spontaneous circulation will return and the patients will survive to discharge, a recent study found.

Researchers used the Get With the Guidelines-Resuscitation database to identify 25,095 patients who had cardiac arrest in the hospital with asystole (55%) or pulseless (45%) electrical activity as the initial rhythm (non-shockable rhythm). Patients were excluded if they had a repeat cardiac arrest; if their arrest occurred in the ED, ICU, or surgical unit; or if they received vasopressin before their first dose of epinephrine. The main outcome was survival to discharge; secondary outcomes included return of spontaneous circulation (presence of palpable pulses for 20 minutes), 24-hour survival, and survival with favorable neurological status at discharge. Results were published online May 20 by BMJ.

The median time to administration of the first epinephrine dose after recognition of cardiac arrest was 3 minutes, and the median number of doses administered was 3. Forty-nine percent of patients had sustained return of spontaneous circulation; 27% survived to 24 hours and 10% survived to discharge, usually with favorable neurological status. Survival rates decreased as the amount of time to epinephrine dose increased in 3-minute intervals. The adjusted odds ratio (OR) for survival was 1.0 for 1 to 3 minutes to dose (reference group); 0.91 for 4 to 6 minutes to dose (P=0.055); 0.74 for 7 to 9 minutes to dose (P<0.001); and 0.63 for more than 9 minutes to dose (P<0.001). This stepwise effect was seen across the other outcome variables, as well.

Current quality measures regarding resuscitation focus almost exclusively on defibrillation, the authors noted. However, they wrote, “defibrillation is not useful for most cardiac arrests”. With such a large proportion of cardiac arrests being non-shockable rhythms, future quality metrics could conceivably focus on shortening the time to administration of epinephrine in these patients.”

CDC targets 5 parasitic infections

The CDC has targeted 5 neglected parasitic infections in the United States as priorities for public health action: Chagas disease, cysticercosis, toxocariasis, toxoplasmosis, and trichomoniasis.

The infections were chosen for targeting based on their prevalence, severity, or the possibility of improving treatment and prevention. They were analyzed individually by CDC scientists in a recent special supplement to the American Journal of Tropical Medicine and Hygiene.

The articles highlight the infections' epidemiologic profiles, modes of transmission, prevention and control strategies, and shared characteristics, including the large numbers of people in the U.S. who may be at risk, the potential for underreporting and misdiagnoses because of lack of physician awareness and optimal diagnostics, and the lack of interventions to prevent or treat disease.

Perhaps most relevant to hospitalists is the article on cysticercosis, which almost always presents as neurocysticercosis. Seizures are the most common manifestation, although headaches, hydrocephalus, or focal neurologic signs are also common. Past research from Oregon and California suggests that incidence of hospitalization for neurocysticercosis ranges from 0.2 to 1.1/100,000 persons in the general population and 1.5 to 5.5/100,000 in the Hispanic population. Another study of 1,801 U.S. emergency department patients (in various locations) treated for seizure disorders found that 2.1% of them had neurocysticercosis.

An editorial accompanying the articles called for some specific improvements in diagnostic tests and treatments, including better tests and drugs for Chagas disease, new tests and drugs for drug-resistant trichomoniasis, and evaluation of drug regimens for pregnant women.