Recent Research

High-intensity statins after CHD hospitalization, beta-blockers at discharge and 30-day readmissions, metoclopramide and pneumonia in stroke, and more.

High-intensity statins often not taken after CHD hospitalization, study finds

Patients who are hospitalized for coronary heart disease (CHD) often don't fill prescriptions for high-intensity statins after discharge, according to a study.

Researchers used a 5% random sample of Medicare beneficiaries between age 65 and age 74 to conduct a retrospective cohort study examining rates at which high-intensity statin prescriptions are filled after CHD hospitalization. Beneficiaries were included in the study if they filled a prescription for statins after myocardial infarction or coronary revascularization in 2007, 2008, or 2009. The authors defined high-intensity statins as atorvastatin, 40 to 80 mg; rosuvastatin, 20 to 40 mg; and simvastatin, 80 mg. The study results were published in the Jan. 27 Journal of the American College of Cardiology.

A total of 8,762 Medicare beneficiaries who filled a statin prescription after a CHD event were included in the study. Twenty-seven percent of first statin prescription fills after discharge were for a high-intensity statin, while 35% of the 8,019 patients with 365 days of follow-up filled a high-intensity statin prescription any time after hospital discharge. Patients who had taken a high-intensity statin before their CHD event were more likely to fill a high-intensity statin prescription afterward than patients who had not been taking statins before their hospitalization or those who had been taking low- or moderate-intensity statins (80.7%, 23.1%, and 9.4%, respectively). Multivariable adjusted risk ratios for filling a high-intensity statin prescription were 4.01 (95% CI, 3.58 to 4.49) for patients taking high-intensity statins previously and 0.45 (9%% CI, 0.40 to 0.52) for those taking low- or moderate-intensity statins previously, compared with patients who were not taking statins before their hospitalization.

The authors noted that data on statin prescriptions came from pharmacy claims, that some instances of low- or moderate-intensity statin use could have been appropriate, that their results are not generalizable to younger patients, and that use of high-intensity statins may have increased since 2009 because of the availability of generic atorvastatin. However, they concluded that a majority of Medicare beneficiaries did not receive a prescription for high-intensity statins after CHD hospitalization, contrary to clinical trial evidence and guideline recommendations, and that patients were more likely to fill a high-intensity statin prescription after discharge if they had taken the drugs before their hospitalization. “Future efforts are needed to better understand the causes of this pattern so that interventions can be designed to improve evidence-based care,” the authors wrote.

The author of an accompanying editorial was concerned by the findings. “It is unlikely that most patients after significant cardiac events would have ignored their physician's advice if they were indeed given a prescription for high-intensity statins, so why did most patients end up on lower-dose therapy?” the editorialist asked. He speculated that treating physicians might not know about the guideline recommendations, might not believe in them because of ongoing controversy about cholesterol targets, might not have prescribed the drugs if patients already had low LDL cholesterol levels, or might be concerned about side effects of statins at high doses. “Although not guideline recommended, it is conceivable that treating physicians wanted to evaluate patient response and tolerance to lower-dose therapy before proceeding to high-intensity statin therapy,” the editorialist wrote. “Finally, physician inertia and/or lack of adequate discharge planning could explain the observed gaps in [guideline-directed medical therapy].”

The editorialist called these gaps “worrisome” and called for actions to improve implementation of these therapies in clinical practice. “Future [coronary artery disease] performance measures should include documentation of evidence for guideline-based therapy use by clinicians tied to pay for performance. Such a strategy has worked for heart failure and it is time now to apply it to patients with [coronary artery disease],” he concluded.

Beta-blockers at discharge didn't increase 30-day readmissions for heart failure patients

Prescribing beta-blockers to heart failure patients at discharge didn't increase their 30-day readmissions, a study found.

Researchers sought to determine if the initial negative inotropic effect of beta-blockers in heart failure patients might increase their 30-day all-cause readmissions. They used data from 3,067 Alabama Medicare patients who had a left-ventricular ejection fraction <45%, and were discharged with heart failure (HF) between July 1, 1998 and Oct. 31, 2001. The researchers then used propensity-score matching to derive a cohort of 380 patients who received beta-blockers at discharge and 380 who didn't. The main outcome was 30-day all-cause hospitalization; secondary outcomes were all-cause mortality, heart failure hospitalizations, and a combined end-point of all-cause readmissions or all-cause mortality.

There was no significant association between use of beta-blockers and 30-day readmissions (hazard ratio [HR], 0.87; 95% CI, 0.64 to 1.18) or heart failure readmission (HR, 0.95; 95% CI, 0.57 to 1.58), but there was a significant association between beta-blockers use and lower 30-day, all-cause mortality (HR, 0.29; 95% CI, 0.12 to 0.73). Also, in the 4-year post-discharge period, patients taking beta-blockers had fewer deaths (HR, 0.81; 95% CI, 0.67 to 0.98) and a lower combined outcome of all-cause readmissions or all-cause mortality (HR, 0.87; 95% CI, 0.74 to 0.97). Results were published online Dec. 29 by the American Journal of Medicine.

Study limitations included lack of data on post-discharge use of medications, and the fact that low numbers of mortality events in 30 days may have inflated hazard ratios erroneously, the authors wrote. The mean age of patients in the study was 73 years, thus the results suggest that older, hospitalized patients with systolic heart failure can be prescribed beta-blockers without concern that doing so will increase 30-day readmissions, the authors concluded.

Metoclopramide may help reduce pneumonia in patients with stroke and nasogastric tubes

Metoclopramide may help reduce pneumonia in patients with stroke who are fed via nasogastric tubes, according to a small study.

Between September 2008 and September 2011, researchers performed a double-blind, randomized, placebo-controlled trial in patients within 7 days of stroke onset and 48 hours after insertion of a nasogastric tube. Patients were assigned to receive 10 mg of metoclopramide (10 mL of colorless solution) or placebo (10 mL of saline solution) through the nasogastric tube 3 times per day for 21 days or until no additional nasogastric feeds were given. Clinicians recorded clinical signs of pneumonia each day and diagnosed pneumonia if relevant clinical signs, high inflammatory markers, and new infiltrates on chest radiograph were present. The study's primary outcome was number of pneumonia episodes in each treatment group; secondary outcomes were episodes of witnessed aspiration, highest white blood cell counts and C-reactive protein levels during follow-up, antibiotic days, neurological deficit at 21 days, and final clinical outcome. Study results were published online by Stroke on Dec. 16.

A total of 60 patients were randomly assigned to a study group, 30 to metoclopramide and 30 to placebo. The mean age was 78 years, and 63.3% were women. The mean National Institutes of Health (NIH) Stroke Scale score was 19.25. Ninety-eight patients had a nasogastric tube for 1 week or more, 31 (51%) had a nasogastric tube for 2 weeks, and 19 (31%) had a nasogastric tube for 3 weeks. Overall, the placebo group had significantly more pneumonia episodes than the metoclopramide group (rate ratio, 5.24; P<0.001). Patients in the metoclopramide group also had lower aspiration rates (rate ratio, 20.54; P=0.003), better oxygen saturation (P<0.001), better inflammatory markers (P=0.16 for white blood cell count and P=0.014 for C-reactive protein level), and better scores on the NIH Stroke Scale (P=0.043) than those in the placebo group. Mortality did not differ significantly between the groups (odds ratio, 1.85; P=0.292).

The authors noted that their study was small and not fully blinded and that a formal sample size was not calculated, among other limitations. However, they concluded that metoclopramide may reduce pneumonia rates and improve other clinical outcomes in patients who have had a subacute stroke and are being fed through a nasogastric tube. They noted that their findings should be confirmed in larger, multicenter randomized blinded trials. “If confirmed, the findings could lead to a new approach to the prevention of pneumonia in patients with stroke fed via [nasogastric tubes],” they wrote.

Clarithromycin may cause serious adverse events when taken with certain statins

Clarithromycin may cause serious adverse events when taken with rosuvastatin, pravastatin, or fluvastatin, according to a study.

Researchers used large health care databases to determine whether increased frequency of adverse events was seen when clarithromycin, which inhibits cytochrome P450 3A4 (CYP3A4), was taken with a statin that CYP3A4 does not metabolize. Included patients were from a population-based cohort who were taking rosuvastatin, pravastatin, or fluvastatin and received a new prescription of clarithromycin or azithromycin between 2002 and 2013. Because azithromycin does not inhibit CYP3A4, patients prescribed this drug served as the control group. The study's primary outcomes, all in 30 days after co-prescription, were hospital admission for rhabdomyolysis, acute kidney injury, or hyperkalemia, all based on diagnostic codes, and all-cause mortality. The study results were published online Dec. 22 by CMAJ.

Overall, 104,041 people were included in the study, 51,523 in the clarithromycin group and 52,518 in the azithromycin group. Seventy-six percent of patients were prescribed rosuvastatin (76%), 21% were prescribed pravastatin, and 3% were prescribed fluvastatin. The median dosage of clarithromycin and azithromycin was 1,000 mg/d for 10 days and 300 mg/d for 5 days, respectively. Patients who were prescribed both clarithromycin and 1 of the 3 studied statins had a higher risk of hospital admission with acute kidney injury (adjusted relative risk, 1.65; 95% CI, 1.31 to 2.09) and hyperkalemia (adjusted relative risk, 2.17; 95% CI, 1.22 to 3.86), as well as all-cause mortality (adjusted relative risk, 1.43; 95% CI, 1.15 to 1.76), compared with patients in the control group. No statistically significant increase in relative risk was seen for hospital admission with rhabdomyolysis (adjusted relative risk, 2.27; 95% CI, 0.86 to 5.96).

The authors noted that the absolute risk increase for each of the primary outcomes was small. In addition, they pointed out that their findings may not have been causal, that some confounding variables may not have been measured, and that their results apply only to older adults. However, they concluded that the combination of clarithromycin and a statin that is not metabolized by CYP3A4 is associated with a modest increase in deaths and hospital admissions due to adverse events. “Although the US FDA recommends the use of non-CYP34-metabolized statins as a safer alternative when taken concurrently with CYP3A4 inhibitors, our findings indicate that unintended adverse events may still occur, possibly because of additional mechanisms of drug interactions independent of the CYP3A4 pathway,” the authors wrote. Specifically, they noted that clarithromycin may also inhibit the liver-specific organic anion-transporter polypeptides (OATP1B1 and OATP1B3), which are considered the key rate-limiting transporters that govern the hepatic uptake of statins. “To prevent toxicity, the use of azithromycin or another antibiotic that does not interact with statins can be considered,” they said.

Hypertension often undertreated after hospitalization for stroke

Patients who were hospitalized for an ischemic stroke often had a systolic blood pressure (SBP) above 160 mm Hg at discharge and at subsequent outpatient visits, a study found.

Researchers in the Veterans Health Administration analyzed 3,153 patients hospitalized and discharged after an acute ischemic stroke. The patients' outpatient visits in the year after discharge were analyzed for the patients' SBPs and the clinicians' use of opportunities for treatment intensification (whether antihypertensive therapy was increased in response to a reading >160 mm Hg or multiple readings >140 mm Hg). Results were published online by Stroke on Dec. 30.

Overall, at discharge, 62.6% of the patients had a SBP <140 mm Hg, 26.0% had an SBP between 141 and 160 mm Hg, and 11.4% had an SBP >160 mm Hg. In the year after discharge, 62% of the patients had no opportunities for treatment intensification because their blood pressure never went over 140 mm Hg. However, even among those who left the hospital with an SBP <140 mm Hg, 30% had a treatment intensification opportunity, only 58% of which clinicians acted on. In the middle group (141 to 160 mm Hg), 47% of patients had an intensification opportunity, with only 60% of those resulting in intensification. Finally, in the patients who were discharged with SBP >160 mm Hg, 63% had a treatment intensification opportunity, and 65% of those were acted on.

The study also looked for a relationship between medication adherence and treatment intensification but found none. Among the patients who had an intensification opportunity, about 48% adhered to medications before their stroke, a rate that dropped to 46% after discharge. The results suggest that there are many opportunities to improve stroke patients' hypertension control, and given the relationship between discharge blood pressure and subsequent readings, “the place to affect the most change in the poststroke BP trajectory is before discharge,” the study authors concluded.

They recommended improvements on 3 fronts. First, hospital clinicians should increase efforts to improve hypertension management before discharge. Second, physicians in all settings should assure that patients are on the correct medications and titrate those medications to achieve blood pressure control. Finally, more work should be done on improving adherence, including counseling about adherence and assessment of barriers to taking medication, some of which might have resulted from the stroke itself.

Invasive management best for AMI patients with cardiogenic shock

Invasive management is superior to conservative management of patients with cardiogenic shock complicating acute myocardial infarction, a study found.

Researchers analyzed data from 20,644 patients in the Nationwide Inpatient Sample who were discharged between 2002 and 2011 with a primary diagnosis of acute myocardial infarction (AMI) and a secondary diagnosis of cardiogenic shock. About 53% of the patients were age 75 years or older. The researchers used propensity-score matching to assemble a cohort of patients managed invasively versus conservatively. Invasive procedures included cardiac catheterization, percutaneous coronary intervention (PCI), or coronary artery bypass graft (CABG) surgery. The main outcome was in-hospital mortality. Results were published online Dec. 29 by the American Journal of Medicine.

Among patients who underwent invasive management, 58% had PCI, and 22% had CABG. Intra-aortic balloon pump was used in 57.4% of patients who were managed invasively and 4.7% of those managed conservatively. Patients with invasive management had a 59% reduced odds of in-hospital mortality, compared to those managed conservatively (mortality: 37.7% vs. 59.7%; odds ratio [OR], 0.41; 95% CI, 0.39 to 0.43; P<0.0001). Mortality benefit from invasive management was seen both in patients 75 years and older (44% vs. 63.6%; OR, 0.45; 95% CI, 0.42 to 0.49; P<0.0001) and those younger than 75 (30.6% vs. 55.1%; OR, 0.36; 95% CI, 0.33 to 0.39; P<0.0001), but the magnitude of the risk reduction was significantly greater for the younger patients. Within the invasively managed group, there was also a larger mortality risk reduction in patients without diabetes compared to those with diabetes.

The results emphasize the need for aggressive management in the elderly, a high-risk subgroup which physicians may be hesitant to treat aggressively. “Our findings lend support to the recent guidelines that do not make the distinction of age in advocating for an invasive strategy,” the study authors wrote.

Prednisone speeds recovery for inpatients with community-acquired pneumonia

For patients hospitalized with community-acquired pneumonia (CAP), prednisone treatment shortened their time to clinical stability and hospital length of stay, a study found.

The double-blind trial included 785 patients with CAP, hospitalized at 1 of 7 tertiary care centers in Switzerland in 2009 to 2014. They were randomized to either prednisone, 50 mg daily for 7 days, or placebo, with a primary endpoint of clinical stability (stable vital signs for at least 24 hours). Results were published by The Lancet on Jan. 18.

The median time to clinical stability was significantly shorter in the prednisone group than the placebo group (3.0 days vs. 4.4 days; hazard ratio [HR], 1.33; P<0.0001). Time to hospital discharge was also shorter (6 days vs. 7 days; HR, 1.19; P=0.012). The prednisone group had a lower rate of pneumonia-associated complications within 30 days, but the difference was not statistically significant (11 patients on prednisone vs. 22 on placebo; odds ratio [OR], 0.49; P=0.056). Prednisone was associated with a higher rate of inpatient hyperglycemia requiring insulin (19% vs. 11%; OR, 1.96; P=0.0010).

This is the largest trial to confirm the benefits of corticosteroids in CAP, the study authors concluded. Only one previous trial has found conflicting results, possibly because of its results in the subgroup of inpatients admitted directly to the ICU. The benefits of prednisone likely result from the drug's effect on inflammatory cytokines, according to the authors. They noted that use of corticosteroids in CAP improved patient outcomes and reduced hospital costs in this study.

The study “provides valuable evidence” to recommend treatment with prednisone in adults hospitalized with CAP, noted an accompanying comment. However, more research is also needed to assess the impact of corticosteroids on community-acquired pneumonia treated in the outpatient setting and the ICU, as well as on long-term benefit from corticosteroids and the sequelae of pneumonia, the comment said.

Cost-effectiveness model supports universal MRSA decolonization in ICU

Universal decolonization for methicillin-resistant Staphylococcus aureus (MRSA) in ICU patients was more cost-effective than screening-based strategies, a modeling study found.

Researchers compared 3 strategies for preventing MRSA spread: 1) nasal screening with contact precautions for positive patients, 2) nasal screening with contact precautions and targeted decolonization for positive patients, and 3) universal decolonization without screening. Using data from a large, randomized trial implementing these strategies and a decision-analytic model, they calculated the quality-adjusted life-years (QALYs) that would be gained by prevented MRSA infections. Results were published in the February Critical Care Medicine.

Universal decolonization would reduce MRSA infections by 1.31% and 1.59% over targeted decolonization and just contact precautions, respectively, the model showed. That would be a savings of $16,203 per QALY compared to targeted decolonization and $14,562 per QALY compared to contact precautions. The study authors calculated between $185 and $193 in savings per patient, which means a 12-bed ICU with 700 annual admissions could save between $129,500 and $135,100 annually using universal decolonization.

The authors concluded that universal decolonization outperforms the other strategies and would likely be cost-effective even at a low threshold of willingness to pay per QALY, based on probabilistic analysis. The results are only based on modeling and so should be confirmed by randomized trials, the study authors cautioned. They also noted that only data from the ICU were used and that bacterial resistance to decolonization methods would affect the findings. Still, the results add economic information to the existing data supporting decolonization without screening. “The debate is ongoing, but there is a pool of evidence that universal decolonization programs may have a place in the management of MRSA epidemics in ICUs,” the study authors concluded.

Improved mortality rates in diabetic ICU patients appear to be independent of glucose control, study finds

Improved mortality rates in diabetic ICU patients over the past decade appear to be independent of glucose control, according to a study.

Researchers performed a serial, cross-sectional observational study of adult, nonobstetric discharges from Yale-New Haven Hospital between Jan. 1, 2000, and Dec. 31, 2010. The study's objective was to examine whether decreased mortality affected all patients with diabetes and whether any factors could explain it. Main outcome measures were in-hospital mortality, inpatient glycemic control (i.e., percentage of days with glucose levels below 70 mg/dL, above 299 mg/dL, 70 to 179 mg/dL, and SD of glucose measurements), and outpatient glycemic control as determined by HbA1c level. The study results were published online Jan. 28 by the Journal of Hospital Medicine.

A total of 322,938 admissions were analyzed for the study, and of these, 76,758 (23.8%) involved diabetic patients. Among the 54,685 ICU admissions, the overall mortality rate was 9.9% (10.5% in diabetic patients and 9.8% in nondiabetic patients). Among the 14,364 ICU patients with diabetes, a 7.8% relative reduction in odds of mortality was observed for each successive study year, after adjustment for age, race, payer, length of stay, service assignment (surgical vs. medical), discharge diagnosis, and comorbid conditions (odds ratio, 0.923; 95% CI, 0.906 to 0.940). Patients without diabetes, meanwhile, had a 2.6% yearly reduction in odds of mortality (odds ratio, 0.974; 95% CI, 0.963 to 0.985; P<0.001 for the interaction). The significant decrease in mortality persisted in diabetic ICU patients after adjustment for both inpatient and outpatient glycemic control (odds ratio, 0.953; 95% CI, 0.914 to 0.994).

The authors noted that improvements in glucose management in the study may have been too small for a mortality benefit, that clinical endpoints such as infections and complications were not included, that that postdischarge mortality was not examined, among other limitations. However, they concluded that the disproportionate decrease in mortality in diabetic ICU patients over time does not appear to be related to improved outpatient or inpatient glycemic control.

“Although improved glycemic control may have other benefits, it does not appear to impact in-hospital mortality,” the authors wrote. “Our real-world empirical results contribute to the discourse among clinicians and policymakers with regards to refocusing the approach to managing glucose in-hospital and readjudication of diabetes-related quality measures.”

‘Patient navigator’ intervention reduces readmissions for some safety-net patients

Older patients who were cared for at safety-net hospitals and were at high risk for readmission had lower 30-day readmission rates if they received coaching and assistance from community health workers acting as patient navigators, but the same benefits were not seen among younger patients, a study found.

Researchers performed a randomized, controlled trial in an academic public safety-net system with 2 hospitals to determine whether a patient navigator intervention would improve readmission rates among those at high risk. General inpatients were considered at high risk for readmission if they had 1 or more of the following risk factors: age older than 60 years, in-network inpatient admission in the past 6 months, a length of stay of at least 3 days, or an admission diagnosis of heart failure or chronic obstructive pulmonary disease.

Those assigned to the patient navigator group received coaching and assistance via hospital visits and weekly telephone calls up to 30 days after discharge that addressed discharge preparation, medication and symptom management, scheduling of follow-up appointments, and communication with primary care. The study's main outcome measures were in-network 30-day hospital readmissions, while secondary outcomes included outpatient follow-up rates. Study results were published online Jan. 24 by the Journal of General Internal Medicine.

A total of 1,937 patients were randomly assigned, 747 to the patient navigator group and 1,190 to the control group. Of these, 585 in the patient navigator group and 925 in the control group were included in the analytic sample. The researchers analyzed outcomes for the entire sample and by age; 425 patients in the intervention group and 584 controls were older than age 60, and 160 patients in the intervention group and 341 patients in the control group were age 60 or younger.

Thirty-day readmission rates did not differ overall between the intervention and control groups. However, a statistically significant difference was seen by age. Patients in the intervention group who were older than age 60 had an adjusted absolute decrease of 4.1% (95% CI, −8.0% to −0.2%) in readmission rates and increased rates of 30-day outpatient follow-up. Patients in the intervention group who were 60 years of age or younger, meanwhile, had an adjusted absolute increase in readmission rates of 11.8% (95% CI, 4.4% to 19.0%) and no change in rates of 30-day outpatient follow-up.

The authors noted that their data covered only in-network readmissions, that discharge coordinators were not blinded to the study group, and that their results may not be generalizable to all settings, among other limitations. However, they concluded that the patient navigator intervention evaluated in their study was associated with reduced readmission rates in older patients but higher rates in younger patients. The study results raise questions about younger patients covered under public insurance, the authors said.

“Did their readmissions address unmet medical needs? Could these readmissions have been prevented with more intensive community-based care? Were our results shaped by previous excluded populations, such as non-English speakers, those leaving [against medical advice], or the homeless?” the authors wrote. “Future studies that address these questions may help to optimize transitional care of vulnerable patients across all age groups.”

Nonpharmacological, multicomponent interventions reduced delirium, prevented falls

Nonpharmacological, multicomponent interventions appeared to be effective at reducing delirium and preventing falls in hospitalized older patients, a study found.

Researchers conducted a meta-analysis of 14 articles that involved 4,267 patients with an average age of nearly 80 years at 12 acute medical sites and surgical wards. Results appeared online Feb. 2 in JAMA Internal Medicine.

Eleven studies showed significant reductions in delirium incidence (odds ratio [OR], 0.47; 95% CI, 0.38 to 0.58) associated with multicomponent, nonpharmacological interventions. Four randomized or matched trials found a reduction in delirium incidence of 44% (OR, 0.56; 95% CI, 0.42 to 0.76). The rate of falls decreased significantly among intervention patients in 4 studies (OR, 0.38; 95% CI, 0.25 to 0.60); in 2 randomized or matched trials, the rate of falls was reduced by 64% (OR, 0.36; 95% CI, 0.22 to 0.61). Length of stay and institutionalization after discharge also trended in favor of the intervention groups, with a mean difference of −0.16 (95% CI, −0.97 to 0.64) day and a 5% lower chance of institutionalization (95% CI, 0.71 to 1.26) in the intervention patients.

The authors called the effect of intervention strategies on delirium incidence “striking,” with a highly significant 53% odds reduction. In 2008, there were 13.2 million hospital discharges of older patients in the U.S., with a mean hospital stay of 5.5 days, so the authors estimated that about 1 million cases of delirium in the hospital could have been prevented by multicomponent nonpharmacological interventions each year, resulting in Medicare savings of approximately $10,000 per case prevented, or $10 billion annually. “Few intervention strategies have proved effective for fall prevention in the hospital,” the authors wrote. “Notably, 12 of 14 studies examined in this meta-analysis included exercise interventions designed to enhance mobility.”

In a related commentary, an author noted that components of these interventions, such as frequent orientation of patients to time, place, and situation; early mobilization; attention to hearing and visual deficits and aids as appropriate; preservation of sleep-wake cycles; and adequate hydration, are likely already occurring some of the time at most of the hospitals. But the key to their effectiveness is using them consistently.

“Changing practice in the acute care setting is never easy and is often fraught with great uncertainty about risks and benefits to patients and the system,” the editorial concluded. “However, with respect to delirium prevention, the results [of this study] suggest that it may no longer be a matter of evidence or knowing what to do. It may now be a matter of convincing hospitals and health care professionals to just do it.”