Malnutrition, diuretics, and more

Research summaries from ACP Hospitalist Weekly.

Malnutrition common among patients with ACS, linked to worse outcomes

Patients with acute coronary syndrome (ACS) are often malnourished, which may increase their risk for cardiovascular events and death, a recent study found.

Researchers in Spain examined consecutive patients with ACS to report prevalence, clinical associations, and prognostic consequences of malnutrition. They defined ACS as unstable angina, non-ST-segment elevation myocardial infarction, or ST-segment elevation myocardial infarction. They assessed nutritional status by using the Controlling Nutritional Status (CONUT) score, the Nutritional Risk Index (NRI), and the Prognostic Nutritional Index (PNI) to determine relationships between risk for malnutrition and all-cause mortality and major cardiovascular events (MACEs), defined as cardiovascular death, reinfarction, or ischemic stroke. The study results were published in the Aug. 18, 2020, Journal of the American College of Cardiology.

The study included 5,062 consecutive white patients with ACS, 74.5% of whom were men. Mean age was 66.2 years. Twenty-seven patients (0.5%) were underweight, 1,139 (22.5%) were normal weight, 2,357 (46.6%) were overweight, and 1,539 (30.4%) were obese. According to the CONUT score, NRI, and PNI, respectively, 11.2%, 39.5%, and 8.9% of patients were considered moderately or severely malnourished, and 71.8% were considered to have at least mild malnutrition by at least one score. Worse malnutrition scores were most strongly related to a lower body mass index, but moderate or severe malnourishment was seen in between 8.4% and 36.7% of patients with a body mass index of 25 kg/m2 or higher, depending on which nutritional index was used. A total of 830 patients (16.4%) died and 1,048 (20.7%) experienced MACEs during a median follow-up of 3.6 years (interquartile range, 1.3 to 5.3 years).

Moderate and severe malnutrition were associated with significantly increased risk for all-cause death when compared with good nutrition (adjusted hazard ratios, 2.02 [95% CI, 1.65 to 2.49] and 3.65 [95% CI, 2.41 to 5.51] for the CONUT score, 1.40 [95% CI, 1.17 to 1.68] and 2.87 [95% CI, 2.17 to 3.79] for the NRI, and 1.71 [95% CI, 1.37 to 2.15] and 1.95 [95% CI, 1.55 to 2.45] for the PNI; P<0.001 for all comparisons). Results were similar for the association between MACEs and malnutrition as detected by the CONUT score and PNI, but not by the NRI. The ability of the Global Registry of Acute Coronary Events risk score to predict all-cause mortality and MACEs was improved when nutritional status was considered.

The authors noted that their single-center retrospective study involved only white patients and that they did not compare the prognostic value of the simple screening tools used with that of more comprehensive nutritional assessments, among other limitations. They concluded that assessing malnutrition could help physicians identify ACS patients who are at higher risk for death and future cardiovascular events and those who might benefit from nutritional support. They called for clinical trials to evaluate the effects of nutritional interventions on outcomes in ACS patients.

An accompanying editorial stressed that 48% to 58% of malnourished patients in the study were overweight or obese, noting that while larger girth is often seen as overnutrition rather than undernutrition, poor nutrient quality contributes to malnutrition and is associated with increased death in ACS. “These findings should alert clinicians to recognize and assess malnutrition in patients who are overweight/obese. Then, helping these identified patients receive adequate education and coaching on fundamental nutrition concepts will help decrease their mortality risk,” the editorialists wrote. “Furthermore, this paper is yet another urgent call to action: it is time for the CVD [cardiovascular disease] profession to arm itself with the most cost-effective and powerful tool in the battle against CVD: nutrition and lifestyle medicine.”

CGM system reduced hypoglycemia in high-risk inpatients with type 2 diabetes

Real-time continuous glucose monitoring (CGM) in which data is transmitted wirelessly from the patient's bedside to a centralized monitor at the nursing station decreased hypoglycemia in high-risk inpatients with type 2 diabetes when combined with a simplified hypoglycemia prevention protocol, a randomized trial found.

Researchers randomly assigned insulin-treated patients with type 2 diabetes who were admitted to the general medicine service at the Baltimore Veterans Affairs Medical Center and judged to be at high risk for hypoglycemia to receive CGM (intervention/unblinded group) or point-of-care blood glucose testing (standard-of-care/blinded group). All patients had a CGM device placed. Patients in the intervention group had a smartphone at the bedside that transmitted glucose values to a tablet at the nursing station. In this group, low-glucose alerts were set to less than 85 mg/dL (4.7 mmol/L), and nursing staff were instructed to obtain a point-of-care blood glucose test for hypoglycemia alarms as permitted and to provide at least 15 g of carbohydrates for impending hypoglycemia. In the standard-of-care group, glucometric data was collected using blinded CGM systems with alerts disabled. If the point-of-care reading was less than 85 mg/dL (4.7 mmol/L), nursing staff provided 15 g of carbohydrates. The primary outcome was inpatient hypoglycemia. Results from a planned interim analysis for safety monitoring were published online on Aug. 5, 2020, by Diabetes Care.

Image by Getty Image
Image by Getty Image

Seventy-two participants were included in the interim analysis, 36 in the intervention group and 36 in the standard-of-care group. The intervention group experienced fewer hypoglycemic events (<70 mg/dL [3.9 mmol/L]) per patient (0.67 events/patient [95% CI, 0.34 to 1.30] vs. 1.69 events/patient [95% CI, 1.11 to 2.58]; P=0.024), fewer clinically significant hypoglycemic events (<54 mg/dL [3.0 mmol/L) per patient (0.08 events/patient [95% CI, 0.03 to 0.26] vs. 0.75 events/patient [95% CI, 0.51 to 1.09]; P=0.003), and a lower percentage of time spent below 70 mg/dL (3.9 mmol/L) (0.40% [95% CI, 0.18% to 0.92%] vs. 1.88% [95% CI, 1.26% to 2.81%]; P=0.002) and below 54 mg/dL (3.0 mmol/L) (0.05% [95% CI, 0.01% to 0.43%] vs. 0.82% [95% CI, 0.47% to 1.43%], P=0.017) compared with the standard-of-care group. There were no differences between groups in nocturnal hypoglycemia or time in ranges of 70 to 180 mg/dL (3.9 to 10 mmol/L), 180 to 250 mg/dL (10 to 13.9 mmol/L), and greater than 250 mg/dL (13.9 mmol/L).

One limitation was that 93% of patients were men, although there are no known sex-specific differences in the incidence of inpatient hypoglycemia or in the prevention of hypoglycemia with CGM, the study authors noted. They added that because of the COVID-19 pandemic, the trial was halted shortly after they completed the interim analysis.

“We believe that widespread dissemination of these findings in the context of this health crisis could be important. During this emergency, providers have implemented inpatient use of CGM devices, which is still considered investigational,” the authors concluded, adding that the intervention may be beneficial in this environment to help reduce the need for frequent entry of staff into patient rooms and, consequently, personal protective equipment utilization and risk of exposure and transmission.

For more on use of CGM in hospitals, see the article in this issue.

Loop diuretics may improve outcomes in some older patients with heart failure

Older patients with heart failure who were not taking diuretics before hospital admission may benefit from receiving a loop diuretic prescription at discharge, according to a recent study.

Researchers used the OPTIMIZE-HF registry to study Medicare patients hospitalized for heart failure and examine the relationship between use of loop diuretics and clinical outcomes. (GlaxoSmithKline sponsored OPTIMIZE-HF but had no role in the current study.) Of 25,345 older patients in the registry, 9,866 had not taken diuretics before admission. The researchers excluded 1,083 patients receiving dialysis and 847 patients who were discharged on thiazide diuretics, leaving 7,936 patients, 5,568 who received a prescription for loop diuretics at discharge and 2,368 who did not. Propensity scores for receipt of loop diuretics were estimated and used to assemble a matched cohort of 2,191 patient pairs.

The study's primary outcomes were heart failure readmission, all-cause readmission, and all-cause mortality. A combined end point of readmission or mortality was also examined. Outcomes were measured at 30 and 60 days after hospital discharge. The study results were published in the Aug. 11, 2020, Journal of the American College of Cardiology.

Among the 4,382 matched patients, the mean age was 78 years, 54% were women, and 11% were African American. The 30-day all-cause mortality rate was 4.9% (107 of 2,191) in the loop diuretic group and 6.6% (144 to 2,191) in the no loop diuretic group (hazard ratio [HR] for use of loop diuretics vs. no use, 0.73; 95% CI, 0.57 to 0.94; P=0.016). Risk for 30-day heart failure readmission was significantly lower in the loop diuretic group (HR, 0.79; 95% CI, 0.63 to 0.99; P=0.037), but risk for 30-day all-cause readmission was not (HR, 0.89; 95% CI, 0.79 to 1.01; P=0.081). No statistically significant associations were seen during 60 days of follow-up.

The authors noted that their results could have been affected by confounding, that they did not have access to data on loop diuretic doses or use after hospital discharge, and that their study was limited to Medicare fee-for-service beneficiaries. They concluded that older patients hospitalized for heart failure who were not previously taking diuretics but received a loop diuretics prescription at discharge had better clinical outcomes at 30 days than those who did not receive a prescription. The findings provide new information that could strengthen guideline recommendations and improve clinical outcomes for heart failure patients in the short term, the authors wrote.

An accompanying editorial said that the study “strengthens the observational evidence for diuretics and challenges the expectation that placebo-controlled trials should be the basis for all recommendations, for which diuretics may be analogous to parachutes.” The editorialists speculated that the results could prompt a reexamination of recommendations regarding diuretics in heart failure and could lead to extending their use to include stable patients with a recent history of fluid retention. “Previous recommendations have all specified the current presence of symptoms or signs of fluid retention,” the editorialists wrote. “The new recommendation could both extend the indication to chronic use and expand the purpose to at least include ‘to decrease hospitalizations.’”

Early vasopressor dosing associated with mortality risk in septic shock

Receiving more vasopressors in the first 24 hours after septic shock diagnosis was associated with a higher risk of death, a study found.

The prospective cohort study used data on patients requiring admission to the ICU with septic shock between September 2017 and February 2018 at 32 U.S. hospitals and one hospital in Jordan. All of the included patients were treated with at least one vasopressor (most commonly norepinephrine), and researchers defined dosing intensity as the total vasopressor dose infused across all vasopressors in norepinephrine equivalents. Results were published by Critical Care Medicine on July 16, 2020, and appeared in the October 2020 issue.

Out of 1,639 consecutive patients screened, 616 were included in the results. In the 24 hours after shock diagnosis, patients received a median of 3,400 mL of vasopressors (interquartile range [IQR], 1,851 to 5,338 mL), with a median dosing intensity of 8.5 μg/min norepinephrine equivalents (IQR, 3.4 to 18.1 μg/min). In the first six hours, higher vasopressor dosing intensity was associated with increased risk of 30-day in-hospital mortality, but the strength of association depended on concomitant fluid administration, so there was no association between higher doses and mortality in patients receiving at least 2 L of fluid.

In the first 24 hours, every 10 μg/min increase in vasopressor dosing intensity was associated with an increased risk of 30-day mortality (adjusted odds ratio, 1.33; 95% CI, 1.16 to 1.53), and this association did not vary with the amount of fluid administered. Patients treated with an early high/late low dose pattern had lower mortality rates than those treated with early low/late high dosing or sustained high dosing.

“Taken together, we hypothesize that early aggressive vasopressor titration may be preferred compared to slower titration to high doses, but that this strategy must be accompanied by adequate fluid resuscitation in the early hours after shock onset to avoid potential deleterious effects of high-dose vasopressors. If true, this hypothesis has important implications, given the recent interest in early vasopressors to prevent excessive fluid resuscitation,” the authors wrote.

They noted that the results “are in agreement with previous data that has linked the early administration of vasopressors in lieu of fluid therapy with increased mortality” and that although they couldn't identify a threshold for adequate early fluid resuscitation, the quantity of fluid at which early high vasopressors doses stopped being associated with mortality (2 L) was much lower than that included in early goal-directed therapy protocols (6 L).

However, the authors noted that the observational study was subject to confounding and didn't allow examination of potential interaction mechanisms and therefore should be considered hypothesis-generating only.

Inpatient antibiotic stewardship programs decreased antibiotic use but not infection rates

Antibiotic stewardship programs may have high impact on consumption of the antibiotics they target but less impact on resistance rates of high-profile drug-resistant organisms, a retrospective cohort study found.

Researchers looked at all adult members of Kaiser Permanente Southern California who were hospitalized in nine system hospitals from 2008 through 2016. They measured the impact of staggered antibiotic stewardship program implementation on antibiotic consumption and estimated the effect on infection rates. Date of program implementation was defined as the employment start date of a full- or part-time antibiotic stewardship program pharmacist. Outcomes were the consumption of 18 program-targeted antibiotics and rates of infection with four categories of drug-resistant organisms: extended-spectrum beta-lactamase (ESBL), vancomycin-resistant enterococci (VRE), carbapenem-resistant Enterobacteriaceae (CRE), and multidrug-resistant Pseudomonas aeruginosa. Analyses were adjusted for confounding by time, cluster effects, and patient- and hospital-level characteristics. Results were published online on July 15, 2020, by Clinical Infectious Diseases.

A total of 765,111 hospitalizations were included, 288,257 pre-program and 476,854 post-program. Overall use of antibiotics decreased after program implementation by 6.1% (95% CI, −7.5% to −4.7%) in terms of defined daily dose and by 4.3% (95% CI, −5.4% to −3.1%) in terms of days of therapy. There were 14.5% and 11.0% decreases in use of antipseudomonal agents and 6.5% and 7.5% decreases in anti-methicillin-resistant Staphylococcus aureus agents by defined daily dose and days of therapy, respectively. There were significant decreases in piperacillin-tazobactam use across all consumption measures, as well as reductions in resistance to the drug in Escherichia coli and Klebsiella pneumoniae after program implementation. However, there were no decreases in resistance rates among other antibiotics. In adjusted analyses, there was an overall increase of VRE infection following program implementation (relative rate, 1.37; 95% CI, 1.10 to 1.69). There was no change in the rates of ESBL, CRE, or multidrug-resistant Pseudomonas aeruginosa following program implementation.

Among other limitations, the study included community-acquired infections, which may have been influenced by outpatient and long-term-care prescribing and diluted gains made within the inpatient setting, the authors noted. In addition, the timescale to alter drug resistance is likely to differ by organism and may occur more slowly than the study was able to capture, they said.

“Our work can help set expectations for timelines of [antibiotic stewardship program] impact and suggests that reversion to susceptibility across organisms and antibiotics is likely not uniform. Further, we demonstrate that unintended consequences from compensatory prescribing may occur,” as use of ceftriaxone increased after program implementation, likely to balance reductions in the antipseudomonal agents, they concluded.

Bleeding in year after ACS significantly associated with mortality

In the year after acute coronary syndrome (ACS), bleeding was associated with similar risk of death as myocardial infarction, according to a recent study that included patients who did and didn't undergo percutaneous coronary intervention (PCI).

Researchers used a harmonized dataset of four multicenter randomized trials that had compared antithrombotic strategies in patients with ACS to examine the association between postdischarge bleeding and subsequent all-cause mortality. Bleeding was defined as moderate, severe, or life-threatening bleeding, according to Global Use of Strategies to Open Occluded Coronary Arteries, that occurred at least a week after ACS. The results were published in the July 14, 2020, Journal of the American College of Cardiology.

Image by Getty Images
Image by Getty Images

Of the 45,011 participants, 1,133 had postdischarge bleeding (2.6 events per 100 patient-years), and 2,149 died during follow-up. Patients who had bleeding then had significantly increased risk for mortality both within 30 days (adjusted hazard ratio [HR], 15.7; 95% CI, 12.3 to 20.0) and from 30 days to 12 months (adjusted HR, 2.7; 95% CI, 2.1 to 3.4), regardless of whether they had undergone PCI for their index ACS. This risk for mortality, and its time dependence, was similar to that of patients who had a myocardial infarction after ACS.

“Given their similar impact on patients' prognosis, bleeding avoidance after PCI is as critical as prevention of recurrent ischemic events,” the study authors said. The study also showed the importance of bleeding prevention in patients who don't undergo PCI, whom the authors described as “a vulnerable, understudied group representing a substantial proportion of patients with ACS encountered in routine clinical practice.” They noted that guidance and evidence in this population are limited but suggested that “a pragmatic interpretation of our findings is that bleeding avoidance strategies tested in PCI populations, including short-term [dual antiplatelet therapy] or aspirin-free strategies, should also be considered in medically treated patients with ACS deemed at higher risk for bleeding.”

Both the study authors and those of an accompanying editorial highlighted the increased mortality risk in the first 30 days after bleeding as an important finding. The editorial also pointed out that recurrent myocardial infarction occurred almost three times as often as bleeding among study patients. The editorialists also suggested that research in this area should look at outcomes other than all-cause mortality, such as quality-of-life measures. “Appropriately weighing the risk for future bleeding and ischemic events appears to be the ‘Gordian knot’ in the optimized use of antithrombotic therapies post-ACS,” they wrote.

Inpatient initiation of HIV therapy linked patients with substance use disorder to outpatient care

Antiretroviral therapy initiation in the hospital was associated with linkage to outpatient HIV care in patients with HIV and substance use disorder, but it was not associated with retention in HIV care or viral suppression, a recent analysis of a randomized trial found.

Researchers used data from a randomized clinical trial to look at patients with HIV and substance use disorder from 11 U.S. hospitals. Their secondary analysis focused on factors related to initiating and reinitiating antiretroviral therapy in the hospital and its association with linkage to HIV care, frequency of outpatient care visits, retention in care, and viral suppression. Participants were followed for 12 months. Viral load, CD4 cell count, and HIV care visits were determined by laboratory tests and medical records abstraction, and patient characteristics and behaviors were determined through self-report. Results were published online on June 22, 2020, by Clinical Infectious Diseases.

Of 801 participants, 124 (15%) initiated antiretroviral therapy in the hospital, 80 (65%) of whom were starting antiretroviral therapy for the first time. Hospital initiation of antiretroviral therapy was associated with increased frequency of HIV outpatient care visits at six-month (adjusted odds ratio, 1.39; 95% CI, 1.02 to 1.88) and 12-month follow-up assessments (adjusted odds ratio, 1.53; 95% CI, 1.15 to 2.04). However, it was not significantly associated with retention in HIV care or viral suppression over a 12-month period. The median number of days from discharge to HIV primary care visit was 29 days among those who initiated antiretroviral therapy in the hospital, compared with 54 days among those who did not (P=0.0145).

Participants with hospital-initiated antiretroviral therapy had longer stays compared to participants without (P<0.001). Those recruited in Southern hospitals were less likely than those in non-Southern hospitals to initiate antiretroviral therapy in the hospital (P<0.001), whereas past-year opioid use (P=0.001) and history of substance use disorder treatment (P=0.008) were associated with greater likelihood of hospital antiretroviral therapy initiation.

Limitations of the study include its inability to prove causation and to adjust for unmeasured confounders, the authors noted. They added that despite the study's multisite design and large sample size, results may not generalize to the broader U.S. population or to international settings.

The lack of association with antiretroviral therapy and retention in care and viral suppression over 12 months may be due to a lack of structural and system factors to support these outcomes, the authors noted. Although starting antiretroviral therapy in the hospital may be beneficial in patients living with HIV and substance use disorder, “Our study shows this approach is not widely implemented in hospital settings,” they concluded.

Few patients receiving recommended heart failure therapies after hospitalization

While increasing heart failure treatment intensity reduced risk of death and rehospitalization among hospitalized patients, the use of guideline-recommended dual and triple therapies was low, a study found.

Researchers used a commercial insurance database to conduct a retrospective, observational study of 17,106 patients with heart failure with reduced ejection fraction who had a heart failure-related hospitalization in 2008 to 2016. The study looked at use of beta-blockers, angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), angiotensin receptor neprilysin inhibitors (ARNI), and mineralocorticoid receptor antagonists (MRA) in the year after hospitalization. Use of a medication was defined as at least two fills within any six-month interval or one fill for a 90-day supply in the year after hospital discharge. The study was published by the Journal of the American Heart Association on Aug. 4, 2020.

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Image by Getty Images

Nearly a quarter of patients (23%) received none of the medication classes, 22% received only one, 41% received two, and 13% received all three. Compared with no medication, risk of the primary composite outcome of death or rehospitalization was significantly reduced with monotherapy (hazard ratio [HR], 0.68; 95% CI, 0.64 to 0.71), dual therapy (HR, 0.56; 95% CI, 0.53 to 0.59), and triple therapy (HR, 0.45; 95% CI, 0.41 to 0.50).

Among the patients prescribed any of the medications, 90% received beta-blockers, 74% received ACE inhibitors, ARBs, or ARNIs, and 25% received MRAs. Almost half (46%) of patients who received heart failure medication had no post-discharge dose escalation. The proportion of patients who received 75% or more of the target dose was low, but broadly comparable across treatment intensities (monotherapy, 10%; dual therapy, 12%; triple therapy, 11%).

Primary care physicians ordered approximately half (51%) of all initial post-discharge prescriptions, and cardiologists prescribed 20%. Triple therapy was more likely to be prescribed by a cardiologist compared with monotherapy and dual therapy and was less likely to be prescribed by a primary care physician than a cardiologist. Patients who received no medication had a longer length of stay during rehospitalization (7.7 days) than patients prescribed heart failure medication (monotherapy, 6.6 days; dual therapy, 5.8 days; triple therapy, 5.4 days).

Overall, 59% of patients followed up with a primary care physician within 14 days of discharge, and 23% followed up with a cardiologist. Patients who received no heart failure medication had proportionately fewer primary care encounters within 14 days (52%) of hospital discharge than patients prescribed monotherapy (61%), dual therapy (61%), or triple therapy (61%). After 30 days, about 40% of patients who received no post-discharge heart failure medication and about 25% of patients prescribed medication had not received primary care follow-up.

The authors called for improvements in medication dosing and post-discharge follow-up for these patients. “Even allowing for ‘lag,’ over a quarter of patients had no encounters with their [primary care physician] within 30 days, and approximately one third had an encounter with a cardiologist,” they wrote. “While transitional care supporting early outpatient follow-up is essential, it may also be warranted to bolster specialty care in the year post-discharge.”