Beta-blockers, antibiotic algorithm, and more

Summaries from ACP Hospitalist Weekly.

Beta-blocker choice may affect outcomes in cirrhosis and acute myocardial infarction

Patients with cirrhosis who have an acute myocardial infarction (MI) may have better outcomes with a beta1-selective blocker than with a nonselective beta-blocker, according to a recent study.

Researchers in Taiwan used medical records from a national database to compare outcomes in patients with cirrhosis who were hospitalized for acute MI during 2001 to 2013.

Image by Getty Images
Image by Getty Images

Patients were excluded if they were younger than age 20 years and if they had previous MI, a contraindication to beta-blockers, chronic obstructive pulmonary disease, asthma, or atrioventricular conduction disease. The authors also excluded patients who died during the index admission, whose follow-up was shorter than six months, whose medication ratio for beta1-selective or nonselective beta-blockers was less than 80%, or who switched between beta-blockers.

The study's primary outcomes were cardiovascular events at one and two years, adverse outcomes related to the liver, and all-cause mortality. Results were published Sept. 20, 2018, by the Journal of the American Heart Association and appeared in the Oct. 2, 2018, issue.

After propensity score matching, the analysis included 218 patients taking beta1-selective blockers and 218 patients taking nonselective beta-blockers. At one year, no difference in outcomes was seen between patients in each group. At two years, patients in the beta1-selective blocker group were at lower risk for major cardiac and cerebrovascular events than those taking nonselective beta-blockers (hazard ratio, 0.62; 95% CI, 0.42 to 0.91; P=0.015). This effect was also observed in subgroup analyses by age, sex, comorbid conditions, bleeding from esophageal varices, and cirrhosis severity.

Trends were also noted for better rates of all-cause mortality and liver outcomes in the beta1-selective blocker group versus the nonselective beta-blocker group but did not reach statistical significance.

The authors noted that their study excluded a substantial proportion of patients and involved only patients in Taiwan, among other limitations. “In patients with liver cirrhosis, nonselective [beta]-blockers remain the cornerstone of medical treatment of portal hypertension due to the evidence derived from prospective trials of their efficacy in preventing variceal bleeding,” the authors wrote. However, they said that recent research on portal hypertension has raised concerns about the potentially harmful effects of the drugs in this population.

They concluded that in their study, beta1-selective blockers were associated with lower risk for major cardiac and cerebrovascular events in patients with cirrhosis and acute MI after two years of follow-up, although liver outcomes and mortality rates did not differ significantly.

Algorithm may help guide antibiotic therapy for staphylococcal bacteremia

An algorithm may help guide antibiotic treatment for patients with staphylococcal bacteremia and decrease length of therapy without increasing rates of serious adverse events, a recent study found.

Researchers conducted a randomized trial from April 2011 to March 2017 that included 509 patients (mean age, 56.6 years; 44.4% women) at 15 academic medical centers in the U.S. and one in Spain. Eligible patients were ages 18 years and older and had one or more positive blood cultures for Staphylococcus aureus or coagulase-negative staphylococci. Patients who had known or suspected complicated infection at the time of randomization were excluded.

Participants were randomized to receive algorithm-based therapy (n=255) or usual care (n=254). The algorithm group had predefined diagnostic evaluations, antibiotic selection, and duration of therapy, whereas clinicians treating those in the usual practice group had unrestricted choice of antibiotics, duration, and other aspects of clinical care. Participants with S. aureus were followed for 42 days after the end of therapy, and those with coagulase-negative staphylococcal bacteremia were followed for 28 days.

The primary outcomes were clinical success, as determined by a blinded adjudication committee (tested for noninferiority within a 15% margin), and serious adverse event rates in the intention-to-treat population (tested for superiority). The secondary outcome measure (tested for superiority) was the number of antibiotic days among per-protocol patients with simple or uncomplicated bacteremia. Results were published online on Sept. 25, 2018, by JAMA.

Overall, 480 (94.3%) participants completed the trial. Clinical success was documented in 82.0% of patients assigned to receive algorithm-based therapy and 81.5% of those receiving usual care (difference, 0.5%; one-sided 97.5% CI, −6.2% to ∞), meeting the criteria for noninferiority. Serious adverse events were reported in 32.5% of algorithm patients and 28.3% of usual practice patients (difference, 4.2%; 95% CI, −3.8% to 12.2%). For the secondary outcome, mean duration of therapy was 4.4 days for algorithm-based therapy compared to 6.2 days for usual practice (difference, −1.8 days; 95% CI, −3.1 to −0.6). Limitations of the study include its open-label design and the possibility that repeated exposure to the algorithm influenced clinicians' subsequent management decisions in both groups of patients, the study authors noted.

These results will likely influence future treatment guidelines, according to an accompanying editorial. “However, algorithms cannot simply be applied in a vacuum without ongoing monitoring and adjustment based on an individual patient's clinical course. . . . [F]uture investment in clinical trials targeting optimal antibiotic selection and duration are essential to continued progress,” the editorialists wrote.

Models developed to predict MI patients' length of stay, need for postacute care

Factors present at admission can predict length of stay and need for postacute care among patients with acute myocardial infarction (MI), a recent study found.

The study used the National Cardiovascular Data Registry ACTION (Acute Coronary Treatment and Intervention Outcomes Network) to analyze patients who were discharged alive after hospitalization for acute MI between July 1, 2008, and March 31, 2017. The researchers separated the patients into training and validation cohorts to develop models predicting length of stay and likelihood of discharge to postacute care. Results were published on Sept. 14, 2018, by Circulation: Cardiovascular Quality and Outcomes.

The training cohort included 633,737 patients, 16.8% with a prolonged length of stay (at least seven days) and 7.8% who were discharged to a postacute facility (extended care, transitional care unit, or rehabilitation). Models based on the training cohort had moderate discrimination for predicting prolonged length of stay (C statistic=0.640) and strong discrimination for predicting discharge to postacute care (C statistic=0.827) among the validation cohort. The models' discrimination was similar whether patients had ST-segment-elevation MI or non-ST-segment-elevation MI.

Factors predicting prolonged length of stay (all measured at admission) included older age, heart failure, higher heart rate, systolic blood pressure (a U-shaped association), shock, diabetes, lower glomerular filtration rate, and lower hemoglobin level. Older age, heart failure, higher heart rate, shock, and lower hemoglobin level were also associated with discharge to a postacute facility. Prior cerebrovascular disease was also significantly associated with need for postacute care. Patients with private insurance were more likely to go to a postacute facility than those with no insurance, and those with Medicare or Medicaid coverage were even more likely than those with private insurance.

“These models can be used at the bedside by providers both to improve the quality of care and improve performance in alternative payment models, such as bundled payments, although further development of risk-based protocols and the impact of implementing these models require more study,” the authors said. For example, the expectation of a short length of stay could encourage early coordination with the patient's family, while a predicted need for postacute care could motivate early contact with a skilled nursing facility.

The study was limited by its lack of any measures of functional status or frailty, and the identified variables may be specific to acute MI, the authors said. They also noted the risk of confounding and that the models did not include events that occurred during hospitalization. “Prospective testing of these models is needed to establish how they can improve care coordination and lower costs,” the authors said.

Eosinophil count can predict outcomes for patients hospitalized with C. difficile, study finds

An undetectable eosinophil count at admission for Clostridium difficile is a significant predictor of adverse outcomes, a recent study found.

The retrospective cohort study included 2,065 patients admitted for C. difficile infection through the EDs of two tertiary referral centers in 2015. The patients, who were divided into training and validation cohorts, had a mean age of 63.4 years, and 52.9% were women. They were stratified by whether their admission eosinophil count was greater than 0.0 cells/µL. Results were published by JAMA Surgery on Sept. 12, 2018, and appeared in the December 2018 issue.

Patients with an undetectable eosinophil count at admission had significantly increased in-hospital mortality in both the training (odds ratio [OR], 2.01; 95% CI, 1.08 to 3.73; P=0.03) and validation (OR, 2.26; 95% CI, 1.33 to 3.83; P=0.002) cohorts. Undetectable eosinophil counts were also associated with admission to monitored care settings (OR, 1.40; 95% CI, 1.06 to 1.86), need for vasopressors (OR, 2.08; 95% CI, 1.32 to 3.28), and emergency total colectomy (OR, 2.56; 95% CI, 1.12 to 5.87). In addition to eosinophil count, independent predictors of mortality included increasing comorbidity burden (OR for each 1-unit increase, 1.13; 95% CI, 1.05 to 1.22) and lower systolic blood pressure (OR for each 1-mm Hg increase, 0.99; 95% CI, 0.98 to 1.00) at admission.

The study authors also conducted a subgroup analysis of patients who presented without tachycardia or hypotension and found that an undetectable eosinophil count at admission was associated with increased odds of inpatient mortality (OR, 5.76; 95% CI, 1.99 to 16.64), but elevated white blood cell count of at least 15,000 cells/µL was not. The authors concluded that eosinophil count could be “a simple, widely available, inexpensive” method to identify at admission which patients with C. difficile infection are at highest risk of adverse outcomes, including death.

The authors noted that little has been published in the clinical literature on this topic but that this study's findings “correlate well with the recent discovery in a murine model that peripheral blood eosinophils are depleted in connection with binary toxin produced by certain strains of C difficile, likely through accelerated apoptosis rather than reduced eosinopoiesis.” Prospective studies are need to better control for potential confounders, said the authors, who are currently working on a prognostic score (including eosinopenia) for use in patients admitted with C. difficile. The next question will be whether identifying these high-risk patients leads to improved outcomes, they said.

An accompanying editorial comment praised the authors for validating animal research in humans and observed that the existing clinical prediction rules for C. difficile are suboptimal. The editorialists noted that interventions to restore eosinophil cell counts may eventually be found to have therapeutic potential for patients with C. difficile.

Cardiovascular risks significantly elevated for a month after a sepsis hospitalization

Compared to matched controls, including patients recently hospitalized for other conditions, patients who were hospitalized for sepsis had a higher risk of myocardial infarction and stroke in the four weeks after discharge, a study found.

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Image by Getty Images

The retrospective cohort study used the National Health Insurance Research Database in Taiwan to identify 42,316 patients who were admitted to a hospital with a diagnosis of sepsis in 2000 through 2011. They were each matched with a population control with the same age, sex, and comorbidities, and with a hospital control, who matched them on the same factors and had also been admitted to a hospital on the same day as the sepsis patient. Results were published in the Sept. 10, 2018, CMAJ.

In the 180 days after discharge, 831 of the sepsis patients had a stroke and 184 had a myocardial infarction. Compared with the population controls, sepsis patients had an increased risk for myocardial infarction or stroke, which was highest in the first week after discharge (hazard ratio [HR], 4.78 [95% CI, 3.19 to 7.17]; risk difference, 0.0028 [95% CI, 0.0021 to 0.0034]). The increase in risk decreased rapidly until the 28th day (HR, 2.38 [95% CI, 1.94 to 2.92]; risk difference, 0.0045 [95% CI, 0.0035 to 0.0056]), at which point the risk stabilized. Compared to the hospital controls, the sepsis patients' increased risk was attenuated, but it was still significant until day 36 after discharge (HR, 1.32 [95% CI, 1.15 to 1.52]; risk difference, 0.0026 [95% CI, 0.0013 to 0.0039]).

The risk of myocardial infarction or stroke was consistent across subgroups defined by sex and comorbidities, but younger sepsis patients had a more significant increase in risk than older patients (P=0.0004 for the interaction). The authors noted that the low baseline incidence of myocardial infarction and stroke among young people would create a high relative hazard ratio but that the study also found a higher absolute risk, as a number needed to harm from sepsis, in those ages 20 to 45 years compared to those ages 75 years and older.

The results are in line with previous research findings of increased cardiovascular risk after a sepsis hospitalization, the authors said. The study was limited by the possibility of reverse causation bias, although, to combat this, only myocardial infarction and stroke that developed after discharge were included. Based on the findings, “close monitoring and pharmacologic prevention may be required” in the period after a sepsis hospitalization, the authors said. Such pharmacological prevention might include antiplatelet therapy, but the efficacy of this treatment would need to be studied in a randomized controlled trial, they said, adding that the study's findings should also be validated in other populations.