Recent Research

Ambulatory ECG monitoring after stroke, benefit of ventilator bundle components, alteplase and long-term survival after ischemic stroke, and more.


Ambulatory ECG monitoring may be underused after stroke

Guidelines recommend a minimum of 24 hours of electrocardiographic (ECG) monitoring after stroke to detect atrial fibrillation, but a substantial percentage of patients may not be receiving it, according to a recent study.

Researchers used data from the Ontario Stroke Registry to perform a longitudinal cohort study of consecutive patients who presented to designated stroke centers in Ontario from 2003 to 2013. All patients had a first acute ischemic stroke or transient ischemic attack (TIA) and were in sinus rhythm but were not known to have atrial fibrillation. The study's primary outcome was the proportion of patients who received Holter monitoring for at least 24 hours within 30 days of stroke or TIA. Total duration of ECG monitoring within 90 days after stroke or TIA, temporal trends in monitoring, and use of Holter monitoring versus echocardiography were secondary outcomes. The study results were published in the October Stroke.

Overall, 17,398 consecutive patients met the study's eligibility criteria and were considered to be potential candidates for ECG monitoring. The mean age was 68.8 years, and 45.9% were women. Seventy-five percent of patients had a stroke as their index event, while 25% had a TIA. Two-thirds of patients were hospitalized, and of these, 82.6% were discharged to home or to inpatient rehab. A total of 30.6% (95% CI, 29.8% to 31.4%) received Holter monitoring for at least 24 hours within 30 days after stroke or TIA, and fewer than 1% received ECG monitoring beyond 48 hours. Median time to begin monitoring was 9 days after stroke, and stroke and TIA patients were almost twice as likely to receive echocardiography within 90 days compared with Holter monitoring (odds ratio, 1.8; 95% CI, 1.67 to 2.01).

The authors noted that they could not determine how many patients received telemetry as inpatients and that their findings may not be generalizable to other practice settings. They also pointed out that ECG monitoring is not needed or appropriate in patients with catastrophic stroke, contraindications to anticoagulation, or poor life expectancy and that they could not determine which patients in the database met these criteria. However, they concluded that fewer than one-third of patients in their study received guideline-recommended monitoring after stroke or TIA.

“The underuse of poststroke monitoring over the past decade has likely contributed to an overdiagnosis of stroke events as cryptogenic, an underdiagnosis of [atrial fibrillation], and missed anticoagulant treatment opportunities for secondary stroke prevention,” the authors wrote. “This study underscores the need for clinicians and policymakers to address the gap between recent evidence regarding the effectiveness of ECG monitoring for [atrial fibrillation] detection and real-world practice.”

Some ventilator bundle components may yield more benefit than others, study suggests

Certain components of standard ventilator bundles may have a better effect on outcomes than others, according to a recent study.

Researchers performed a retrospective cohort study of consecutive patients who received mechanical ventilation for at least 3 days at Brigham and Women's Hospital in Boston between Jan. 1, 2009, and Dec. 31, 2013. The goal of the study was to evaluate the association between components of ventilator bundles and ventilator-associated events, time to extubation, mortality while on the ventilator, time to hospital discharge, and in-hospital death. The bundle components examined were head-of-bed elevation, interruption of sedative infusion, spontaneous breathing trials, thromboprophylaxis, stress ulcer prophylaxis, and oral care with chlorhexidine.

Main outcome measures were hazard ratios (HRs) for ventilator-associated events, extubation alive versus ventilator mortality, and hospital discharge versus hospital death. Adjustments were made for demographic characteristics, comorbid conditions, type of unit, illness severity, recent procedures, process measure contraindications, daily markers of clinical status, and calendar year. The study results were published in the September JAMA Internal Medicine.

A total of 5,539 patients were included in the study. Of these, 3,208 (57.9%) were men and 2,331 (42.1%) were women. Mean age was 61.2 years. A total of 770 ventilator-associated events occurred during the study, 313 of which were infection-related ventilator-associated complications and 197 of which were possible cases of ventilator-associated pneumonia. Both interruption of sedative infusion and spontaneous breathing trials were associated with less time to extubation as well as lower risk for ventilator mortality (HRs, 0.51 [P<0.001] and 0.28 [P=0.001]). Spontaneous breathing trials were also associated with lower risk for ventilator-associated events (HR, 0.55; P<0.001).

Head-of-bed elevation and thromboembolism prophylaxis were each associated with less time to extubation but were not associated with ventilator mortality, time to hospital discharge, or hospital mortality. An association was seen between oral care with chlorhexidine and increased risk for ventilator mortality (HR, 1.63; P=0.006) and between stress ulcer prophylaxis and increased risk for ventilator-associated pneumonia (HR, 7.69; P=0.02).

The authors pointed out that their results should be interpreted with caution because their study was observational, because it took place at a single facility, and because data were missing for some processes. However, they concluded that different components of ventilator bundles appear to have different effects on ventilator-associated events and that the classic ventilator bundle should be revisited.

Possible revisions could include greater emphasis on sedative infusion interruptions and spontaneous breathing trials, revision of oral care protocols to exclude chlorhexidine therapy, and reservation of stress ulcer prophylaxis for patients at high, immediate risk for gastrointestinal bleeding, the authors wrote. They also suggested that some interventions not currently included in the classic ventilator bundle, such as conservative fluid management, be considered.

The authors of an accompanying editorial pointed out that patients who received the bundle were not compared with those who didn't receive it and that it is not clear whether bundle components failed due to biological ineffectiveness or challenges in implementation. In addition, they said, the study did not clarify whether the effects of bundle components should be considered additively or in sequence.

“Finally, and perhaps most important, lack of focus on evaluation of the bundle components may be an impediment to the evolution of the bundle itself,” the editorialists wrote. They noted that the study doesn't support removal of any items from the existing bundle “but prompts the need to regularly revisit bundle components with a focus on new developments in the field, reexamination of efficacy of old practices, and how both might be combined into the improved bundle of the future.”

Alteplase treatment associated with slightly improved long-term survival after ischemic stroke

If they survived the acute event, patients who received alteplase within 6 hours of an ischemic stroke were more likely to be alive 3 years later, according to follow-up data from an international trial.

The initial trial randomized 3,035 Australian, European, and British patients with an ischemic stroke to either 0.9 mg/kg of IV alteplase plus standard treatment or standard treatment alone. It ran from May 5, 2000, to July 27, 2011. The new follow-up data analyzed survival rates 3 years after treatment in 1,946 pre-selected British and Scandinavian patients. Results were published in the September Lancet Neurology.

The alteplase group had a significantly higher mortality rate during the first 7 days after treatment (10% vs. 7%; hazard ratio [HR], 1.52; 95% CI, 1.11 to 2.08; P=0.004). However, 3 years after treatment, 47% of the alteplase follow-up group had died, compared to 50% of the standard care group, a nonsignificant difference. Researchers calculated that alteplase treatment was associated with a significantly lower risk of death between 8 days and 3 years after treatment (41% vs. 47%; HR, 0.78; 95% CI, 0.68 to 0.90; P=0.007).

“These results are reassuring for clinicians who have expressed concerns about the effect of alteplase on survival,” study authors said. The survival advantage could be due to better functional outcomes among patients receiving alteplase, although it's also possible that some other factor, such as less healthy patients being more likely to die from intracranial hemorrhage in the acute phase, could have contributed, they noted. Another limitation of the study is that the results do not apply to patients receiving intra-arterial stroke treatment. Still, the study “reinforces the case for thrombolytic treatment,” the authors said.

An accompanying comment noted that the higher risk of death with alteplase actually extended beyond 7 days to about 4 months. This could be due to the patients receiving additional invasive procedures because they had better neurological status, the commenter speculated. He noted the significance of the study finding that the improvement in long-term survival with alteplase was not affected by age, stroke severity, or time to treatment.

Five days of antibiotics for CAP worked as well as physician-directed therapy

Treating community-acquired pneumonia (CAP) with only 5 days of antibiotics resulted in similar success rates as allowing physicians to determine the duration of antibiotics, a recent study found.

The multicenter study was conducted in 4 teaching hospitals in the Basque Country of Spain from Jan. 1, 2012, to Aug. 31, 2013. Patients with CAP were randomized to either a control group in which physicians determined the duration of therapy (n=150) or an intervention group (n=162) in which antibiotics were stopped at 5 days as long as patients had a temperature ≤37.8 °C and no more than 1 sign of clinical instability (e.g., hypotension, tachycardia, tachypnea, and hypoxia). Results were published in the September JAMA Internal Medicine.

The control group took antibiotics for a median of 10 days, compared to 5 in the intervention group. In an intention-to-treat analysis, clinical success rates were similar between the control and invention groups, both at day 10 (48.6% vs. 56.3%; P=0.18) and day 30 (88.6% vs. 91.9%; P=0.33). A per-protocol analysis showed similar success at day 10 (50.4% vs. 59.7%; P=0.12) and day 30 (92.7% vs. 94.4%; P=0.54). To measure outcomes important to patients, the researchers also compared scores on the 18-item CAP symptom questionnaires at day 5, when scores were higher (more CAP symptoms) in the intervention group, and day 10, when scores were not significantly different between groups. The study excluded ICU patients, although about 40% of the patients were class IV or V on the Pneumonia Severity Index. Among these patients, clinical success rates were higher in the intervention group than in the control group at day 30 (intention to treat: 93.1% vs. 80.3%; P=0.04; per protocol: 95.9% vs. 85.2%; P=0.10).

“This study indicates that withdrawing antibiotic treatment based on clinical stability criteria after a minimum of 5 days of appropriate treatment is not inferior to traditional treatment schedules” supporting the safety of recommendations from the Infectious Diseases Society of America and American Thoracic Society, the authors concluded. They noted that lengths of stay and IV antibiotic duration were similar between groups but that readmissions were higher among controls. One limitation of the study was that almost 80% of the patients received quinolones, so the results shouldn't be extrapolated to settings where beta-lactams are widely used.

The study refutes the “illogical dogma” of continuing antibiotic therapy beyond resolution of symptoms, said an accompanying editorial. “There is no evidence that taking antibiotics beyond the point at which a patient's symptoms are resolved reduces antibiotic resistance,” wrote the editorialist. Ideally, antibiotic therapy should be customized to patient response and clinicians “should be encouraged to allow patients to stop antibiotic treatment as early as possible on resolution of symptoms of infection,” the editorialist advocated.

New-onset heart failure patients not receiving CAD testing during or after hospitalization

Most patients hospitalized with new-onset heart failure did not receive testing for ischemic coronary artery disease (CAD) during hospitalization or the following 90 days, a recent study found.

The retrospective cohort study used a database of commercial and Medicare claims to examine 67,161 patients diagnosed with new-onset heart failure during a hospitalization between 2010 and 2013. During hospitalization, only 17.5% underwent testing for ischemic CAD and 2.1% had revascularization. During 90-day follow up, those rates rose to 27.4% and 4.3%, respectively. Stress testing was performed during hospitalization in 7.9% and coronary angiography in 11.1% (90-day rates, 14.6% and 16.5%, respectively). In adjusted analyses, patients with a baseline diagnosis of CAD were more likely to undergo both noninvasive ischemic testing (odds ratio, 1.25; 95% CI, 1.17 to 1.33; P<0.0001) and invasive testing (odds ratio, 1.93; 95% CI, 1.83 to 2.05; P<0.0001).

Given that ischemic testing is recommended for heart failure patients under current guidelines, the results suggest significant underutilization of ischemic CAD testing in such patients, the authors concluded. They noted that the study also found that more than a quarter of studied patients didn't get a 2-dimensional transthoracic echocardiogram, either.

The authors calculated that more than 325,000 new heart failure patients might be being inadequately assessed every year, with potential consequences including underuse of guideline-directed medical therapies and revascularization, leading to unnecessary resource utilization from ED and hospital visits.

These “amazing and troubling” findings might actually be the result of efforts to reduce health care costs, speculated an accompanying editorial, while noting that there was no evidence to determine the causes of the study's results. The editorialist urged physicians to “push for an ischemia work-up and intervention more often than it seems we are doing today.” Both the study and the editorial, which were published in the August Journal of the American College of Cardiology, acknowledged that the study was limited by its use of a claims database.

Vitamin K antagonist may increase bleeding more in older patients

Bleeding risk with a vitamin K antagonist (VKA) may mildly increase after the age of 80 years, and there may also be a sharp increase in the risk of thrombosis in the same age group, a study found.

Researchers conducted a matched cohort study of patients at a thrombosis service in the Netherlands. A total of 1,109 patients ages 90 years or older who were treated with a VKA were randomly matched 1:1:1 with 1,100 patients ages 80 to 89 years and 1,104 patients ages 70 to 79 years based on duration of treatment. The primary outcome was a composite of clinically relevant nonmajor and major bleeding. Secondary outcomes included thromboses and quality of VKA control. Results were published in the August JAMA Internal Medicine.

Compared with patients ages 70 to 79 years, those ages 80 to 89 years had a similar risk of bleeding, whereas patients ages 90 years or older had a mildly increased risk of bleeding, the study found. Patients in their 80s and 90s had a markedly higher risk of thrombosis than did patients in their 70s.

During 6,419 observation-years, 713 of the 3,313 patients had 1,050 bleeding events. Patients ages 70 to 79 years had an event rate per 100 patient-years (ER) of 14.8. The risk of bleeding was not significantly increased in patients ages 80 to 89 years (ER, 16.7; hazard ratio [HR], 1.07; 95% CI, 0.89 to 1.27) and was mildly increased in patients ages 90 years or older (ER, 18.1; HR, 1.26; 95% CI, 1.05 to 1.50). The point estimate of event rates for major bleeding, including fatal bleeds, for those ages 70 to 79 years was 0.9, which was comparable with those for patients ages 80 to 89 years (ER, 1.0; HR, 1.09; 95% CI, 0.60 to 1.98) and ages 90 years or older (ER, 1.1; HR, 1.20; 95% CI, 0.65 to 2.22).

Eighty-five patients (2.6%) developed a thrombotic event. Risk of thrombosis was higher for patients in their 90s (HR, 2.14; 95% CI, 1.22 to 3.75) and 80s (HR, 1.75; 95% CI, 1.002 to 3.05) than for patients in their 70s. VKA control became significantly poorer as age increased, which partly explained the increased bleeding risk in patients ages 90 years or older but not the increased risk of thrombosis, the authors wrote.

An editorial concluded that clinicians are successfully identifying very old patients who can be given anticoagulation with relative safety. However, researchers know little about patients whom clinicians choose not to treat with anticoagulation.

“The specter of iatrogenic hemorrhage and preventable thrombosis looms large when discussing anticoagulation at any age,” the editorial concluded. “Patients and clinicians will benefit greatly from robust and generalizable data when considering these nuanced decisions.”