Recent Research

Women and stroke care, frailty as a predictor of cardiac surgery outcome, cost-effectiveness of heart failure therapy, and more


Women were less likely to receive thrombolysis and had longer door-to-needle time, study finds

Although men and women received comparable stroke care overall, women were less likely to receive thrombolysis and had longer door-to-needle and assessment times in the ED, according to a recent registry study.

Using the Florida–Puerto Rico Stroke Registry, researchers studied 51,317 patients (49% women) with a final diagnosis of acute ischemic stroke. Registry data were collected from January 2010 to September 2014 from 64 hospitals in Florida and nine in Puerto Rico. Results were published online on Aug. 23, 2016, by Stroke and appeared in the January 2017 issue.

Researchers evaluated the sex-specific differences in risk factors, presentation, thrombolysis rates, and performance on seven Get With the Guidelines stroke care measures. They used the composite variable of defect-free care to determine the proportion of patients receiving all applicable stroke measures.

Women in the study were older, were more likely to be non-Hispanic black, and had a higher prevalence of hypertension, atrial fibrillation, and previous stroke or transient ischemic attack compared to men. They were less likely than men to be smokers and to have previous coronary artery disease or myocardial infarction.

Although women received a similar overall quality of stroke care compared to men, they were less likely to receive thrombolysis (adjusted odds ratio [OR], 0.92; P=0.02) or to have a door-to-needle time less than one hour (adjusted OR, 0.83; P=0.02). Of the 5,003 patients (10%) who received intravenous tissue plasminogen activator, women had a longer median door-to-needle time than men (73 minutes vs. 69 minutes; P=0.005). Women also had longer assessment times in the ED than men, as measured by the likelihood of having a door-to-computed tomography time of 25 minutes or less (adjusted OR, 0.86; P<0.0001).

In total, 77.8% of women received defect-free care, compared with 78.5% of men (adjusted OR, 0.96; P=0.04). Women also received a lower quality of care in all of the predefined measures compared to men, although the differences were statistically significant for only early antithrombotic treatment (P<0.001), antithrombotics at discharge (P<0.001), anticoagulation at discharge (P=0.005), and statins at discharge (P<0.0001). These differences did not meet the prespecified threshold for clinical significance.

The researchers noted limitations to the study, such as the likelihood that hospitals participating in the voluntary stroke registry have more of an interest in improving stroke care than those not participating. The study population also had a higher representation of Hispanics and non-Hispanic blacks than the general U.S. population.

Frailty may help predict outcomes after cardiac surgery in older adults

Frailty as assessed by mobility, disability, and nutritional status may help predict outcomes after major and minimally invasive cardiac surgery in older patients, according to a recent study.

Researchers performed a systematic review to evaluate the evidence supporting several frailty instruments used to predict outcomes in older adults having cardiac surgery. MEDLINE and EMBASE were searched without language restrictions through May 2, 2016. Cohort studies were included if they looked at the association between frailty and death or functional status (as assessed by Activities of Daily Living, the Duke Activity Status Index, the Kansas City Cardiomyopathy Questionnaire, or New York Heart Association class) at six months or longer in patients at least 60 years of age after major or minimally invasive cardiac surgery. Coronary artery bypass grafting and open-valve surgery were classified as major procedures and transcatheter aortic valve replacement was classified as minimally invasive surgery.

Results were published early online Aug. 23, 2016, by Annals of Internal Medicine and appeared in the Nov. 1, 2016, issue.

For both major and minor surgery, mobility, disability, and nutrition were frequently assessed domains of frailty. Nine frailty instruments were evaluated in 18,388 patients from eight studies who were undergoing major cardiac surgery. Mean age of patients ranged from 62 to 79 years. In this group, moderate-quality evidence supported assessment of mobility or disability, and very low- to low-quality evidence supported use of a multicomponent instrument to predict death or major adverse cardiovascular and cerebrovascular events (MACCEs). None of the eight studies examined functional status in major cardiac surgery patients.

Thirteen frailty instruments were evaluated in 17 studies of 5,177 patients undergoing minimally invasive procedures. Mean age of patients ranged from 79 to 86 years. Moderate- to high-quality evidence supported assessment of mobility to predict death or functional status. Although several multicomponent instruments predicted death, functional status, or MACCEs in this group, the evidence was low- or moderate-quality.

The researchers acknowledged that the frailty assessments in the studies were heterogeneous and that few frailty instruments have been validated. In addition, they noted that multicomponent frailty instruments had limited generalizability, since they were evaluated in study samples from single centers, and that publication bias was possible. However, they concluded that frailty status as assessed by mobility, disability, and nutritional status may predict death at six months or more after major cardiac surgery and functional decline after minimally invasive cardiac surgery.

The authors recommended that clinicians should try to classify patients preoperatively into three groups:

  • extreme risk, with predicted health status after the procedure unlikely to be meaningfully better than without the procedure;
  • high risk, with predicted health status after the procedure likely better than without the procedure, though with a high risk for harm; and
  • low risk, with likely benefit from the procedure but low risk for harms.

They also noted that functional status may be as important to patients as risk for short-term complications or death and that this should factor into assessments.

An accompanying editorial said that the review shows that frailty status is a strong predictor of longer-term mortality and supports frailty assessment in older adults who are considering surgery.

“In addition, to inform surgical decision making for both patients and clinicians, we must assess the effects of frailty on patient-centered outcomes (such as quality of life, function, and cognition),” the editorialists wrote. “Once the decision to have surgery is made, we may better prepare patients and their family members for the possible outcomes and provide needed support, possibly including palliative care. By identifying frailty, we can improve care for our older surgical patients.”

Sacubitril-valsartan appears cost-effective in certain heart failure patients

Treatment with sacubitril-valsartan appears to be cost-effective for reducing cardiovascular mortality and morbidity in patients with New York Heart Association (NYHA) class II to IV heart failure, a recent study found.

Researchers developed a Markov model to perform an independent analysis of the cost-effectiveness of sacubitril-valsartan versus usual care in patients with a mean age of 64 years, NYHA class II to IV heart failure, and reduced ejection fraction (<0.40). Subgroup composition was based on that of the PARADIGM-HF trial, in which 72.9% of patients had class II heart failure, 26.2% had class III heart failure, and 0.9% had class IV heart failure. Patients with class I heart failure (4.7%) who were ill during screening but improved during the study's run-in phase were excluded from the Markov model but included in a sensitivity analysis. Patients in the PARADIGM-HF trial initially received sacubitril-valsartan, 200 mg twice daily, or enalapril, 10 mg daily. The current study, however, modeled lisinopril, 20 mg daily, as the comparator drug due to its lower cost, wider use, and functionally equivalent benefits. Cost-effectiveness was analyzed in subgroups of patients with class II or class III/IV heart failure. The study's outcome measures were life-years, quality-adjusted life-years (QALYs), hospitalizations for heart failure, and incremental cost-effectiveness ratios. The study results were published online Aug. 30, 2016, by Annals of Internal Medicine and appeared in the Nov. 15, 2016, issue.

In the base-case analysis, the sacubitril-valsartan group had 0.08 fewer heart failure hospitalization, 0.69 additional life-year, 0.62 additional QALY, and $29,203 in incremental costs versus the comparator group, which equaled a cost per QALY gained of $47,053. Cost per QALY gained in sacubitril-valsartan patients was $44,531 in those with NYHA class II heart failure and $58,194 in those with NYHA class III or IV heart failure. Class I patients had a higher risk for cardiovascular death in the sacubitril-valsartan group (decrease in average survival, 0.84 year or 0.57 QALY). In the sensitivity analysis, treatment with sacubitril-valsartan was most sensitive to duration of improved outcomes; cost per QALY gained was $120,623 if duration was limited to the median duration of follow-up (i.e., 27 months). The cost per QALY gained did not exceed $100,000 for variations in any other study parameters.

The authors noted that treatment efficacy was based on a single trial with limited subgroup data and that data on long-term treatment were not available. In addition, they said that they did not model patient transition between NYHA classes, that they based drug costs on wholesale prices, and that they did not evaluate concerns about neurocognitive effects of the drug. However, they concluded that based on their analysis, sacubitril-valsartan appears to be cost-effective for reducing cardiovascular morbidity and mortality in patients with NYHA class II to IV heart failure and reduced ejection fraction. They noted that the treatment value was highest in patients with class II heart failure, who also benefited most from treatment in the PARADIGM-HF trial, and that improved outcomes with the drug would need to be sustained for at least 36 months to keep the cost per QALY below the $100,000 threshold.

Overnight extubations associated with higher mortality risk

ICU patients who were extubated overnight had higher mortality rates than those taken off mechanical ventilation during the day, according to a recent study.

The retrospective cohort study was based on the Project IMPACT database and included more than 97,000 patients from 165 ICUs who were extubated between Oct. 1, 2000, and March 29, 2009. Over the entire time period, 20.1% of the patients were extubated between 7 p.m. and 7 a.m. That percentage decreased over the study period, from 23.2% in 2000-2001 to 18.8% in 2009.

After multivariable adjustment, researchers found that patients who had received mechanical ventilation for less than 12 hours were significantly more likely to be extubated overnight. Among the patients with less than 12 hours of ventilation, reintubation rates were similar whether they were extubated overnight or not, but overnight extubation was associated with higher mortality, both during the ICU stay and the hospital stay (ICU mortality: 5.6% vs. 4.6% [P=0.03]; hospital mortality: 8.3% vs. 7.0% [P=0.01]). The overnight extubations were associated with shorter length of stay in the ICU but no change in overall hospital length of stay for these patients.

Among patients who had been on mechanical ventilation for at least 12 hours, overnight extubation was associated with more frequent reintubation in the ICU (14.6% vs. 12.4%; P<0.001) as well as higher mortality in the ICU (11.2% vs. 6.1%; P<0.001) and in the hospital (16.0% vs. 11.1%; P<0.001). There were no differences in lengths of stay for these patients based on the time of day of extubation. The results were published online Sept. 6, 2016, by JAMA Internal Medicine and appeared in the November 2016 issue.

“As anticipated, no clear benefits were associated with overnight extubation,” the study authors wrote. The results differ from the only previous study of this question, noted both the study and an accompanying editorial. However, that study was conducted in a single medical center with strict weaning and extubation criteria. Palliative extubations represent a potential confounding factor for the current study, but the authors tried to control for this, they said. Another limitation was the age of the data, although the results were supported by sensitivity analyses using data through 2013 from another source.

“Our finding that overnight extubation is associated with higher mortality is of great potential clinical import. Although our study cannot prove causality, our findings raise serious concerns about the routine practice of overnight extubation for many patients in the ICU,” the authors concluded. They noted that the results might not apply to all patient subgroups, and that overnight extubation could be safe or even beneficial in certain situations, such as cardiac surgery.

Measuring procalcitonin at ICU admission associated with lower cost and antibiotic exposure

Patients who had their procalcitonin measured on the day they were admitted to the ICU had shorter length of stay and lower costs than similar ones who didn't, a recent study found.

The retrospective analysis used the Premier Healthcare Database to propensity-score match 33,569 patients who had one or two procalcitonin tests on day 1 of an ICU admission to 98,543 similar patients who didn't have procalcitonin measured. Results were published online in September 2016 by CHEST.

A multivariable regression analysis showed that procalcitonin testing was associated with shorter lengths of stay, both in the hospital (11.6 days vs. 12.7 days; P<0.001) and in the ICU (5.1 days vs. 5.3 days; P<0.03). Although procalcitonin patients had higher laboratory costs by $81, their overall hospital costs were lower ($30,454 vs. $33,213; P<0.001). They also had less antibiotic exposure (16.2 days vs. 16.9 days; P=0.006) and were more likely to be discharged to home (44.1% vs. 41.3%; P=0.006). However, no difference in mortality rates was observed between the procalcitonin-managed group and the matched patients.

It is “not readily apparent” how to interpret procalcitonin's lack of effect on mortality rates, given the other observed benefits, the study authors said. They assumed that procalcitonin was being used to rule sepsis in or out. “One would certainly expect that more rapid identification and management of septic patients would also have translated into improved survival in addition to improved healthcare utilization and cost of care,” they wrote.

Possible explanations (and limitations of the study) include that, because this was a retrospective analysis, differences in severity of illness and chronic health status couldn't be entirely controlled for and differences in treatment couldn't be measured, the authors said. They called for additional research to evaluate the significance and mechanisms of their findings.

Pulmonary embolisms often found in patients with acute COPD exacerbations

A significant percentage of patients with unexplained acute exacerbations of chronic obstructive pulmonary disease (COPD) are found to have a pulmonary embolism, according to a systematic review.

Researchers searched MEDLINE and EMBASE from 1974 to October 2015 and included seven studies of patients with unexplained COPD exacerbations in their review. Out of a total of 880 patients, 16.1% (95% CI, 8.3% to 25.8%) had a pulmonary embolism confirmed by pulmonary CT angiography. (In contrast, other inpatient populations have prevalence rates of 5.7% to 6.0%, the study noted.) Of the identified pulmonary embolisms, 68% were found in the main pulmonary arteries, lobar arteries, or interlobar arteries, sites that have a clear indication for anticoagulant treatment, the study authors noted.

The study was published early online in August 2016 by CHEST.

Patients who were found to have a pulmonary embolism more frequently reported pleuritic chest pain or had signs of cardiac failure than those with only an acute COPD exacerbation. Conversely, having signs of a respiratory infection was associated with lower likelihood of pulmonary embolism. The results show that pulmonary embolisms are relatively common among patients with unexplained COPD exacerbations and thus that this issue merits clinical attention, the study authors said. The study's findings could be helpful in decision making about whether to order pulmonary CT angiography in patients with COPD exacerbations, they added.

The authors noted several possible explanations for the observed association between pulmonary embolism and COPD exacerbations: Systemic inflammation contributes to the development of thrombotic events; glucocorticoids, which are used to treat COPD exacerbations, can increase venous thromboembolism risk; and pulmonary embolism could either trigger or mimic an exacerbation.

Anemia, low hemoglobin linked to increased mortality up to a year after stroke, study finds

At the time of stroke onset, a substantial proportion of patients have anemia, which is associated with increased mortality up to one year after stroke, according to a recent study.

Researchers conducted a registry-based study, as well as a systematic review and meta-analysis, to determine the impact of admission hemoglobin levels and anemia on stroke mortality outcomes. Results were published online on Aug. 17, 2016, by the Journal of the American Heart Association.

The study included 8,013 patients (mean age, 77.81 years; 52.4% female) with acute stroke admitted consecutively between January 2003 and May 2015 to a regional tertiary center in the United Kingdom. Researchers measured mortality at seven days, 14 days, one month, three months, six months, and one year. Inpatient mortality was 21.3%, and 86.7% of patients had ischemic stroke.

On admission, 24.5% of patients had anemia, which was defined according to World Health Organization criteria (hemoglobin <12.0 g/dL in women and <13.0 g/dL in men). Low hemoglobin was defined as being in the lowest quintile of studied patients' hemoglobin levels (<11.7 g/dL for women and <12.4 g/dL for men). Elevated hemoglobin was defined as >15.5 g/dL in women and >17.0 g/dL in men.

In men with ischemic stroke, low hemoglobin levels at admission was associated with higher odds of death at all time points, compared to those with normal hemoglobin levels. High hemoglobin levels were associated with increased odds of mortality at four time points: inpatient, seven days, 14 days, and one month.

In women with ischemic stroke, low hemoglobin levels were associated with mortality at five time points: inpatient, one month, three months, six months, and one year, and elevated hemoglobin was associated with increased mortality at seven days, 14 days, and one month.

In men with hemorrhagic stroke, anemia was associated with increased mortality at one year, and elevated hemoglobin was linked to increased mortality at four time points: inpatient, seven days, 14 days, and one month. In women with hemorrhagic stroke, low hemoglobin levels were associated with increased mortality at all time points, and elevated hemoglobin was associated with increased mortality at three time points: inpatient, six months, and one year.

The systematic review included 20 studies that evaluated the impact of anemia and hemoglobin levels on stroke. Combined with the database study, the total pooled study population included 29,943 participants. Meta-analyses of pooled results showed that anemia is linked to an increased risk of mortality in ischemic stroke (pooled odds ratio, 1.97; 95% CI, 1.57 to 2.47) and hemorrhagic stroke (odds ratio, 1.46; 95% CI, 1.23 to 1.74).

The study authors said that in addition to pathophysiological explanations for the findings, it's plausible the excess mortality risk might result from anemic patients being less likely to be prescribed antithrombotics because of increased risk of bleeding. They also noted limitations to their work, such as how they were not able to fully adjust for treatment effects and how the small number of patients with hemorrhagic stroke may have led to nonsignificant findings. They noted that the optimal interventions for this patient population remain unclear.

EMR-based intervention increased early statins, linked to improved outcomes in ischemic stroke

An electronic medical record (EMR)-based intervention increased early statin administration after ischemic stroke and was associated with improved outcomes, according to a recent study.

Researchers performed a retrospective analysis of a multicenter EMR intervention aimed at increasing early statin administration in patients who had had an ischemic stroke at 20 hospitals in the Kaiser Permanente Northern California health system. Specifically, the stroke EMR order set was changed from “opt-in” statin ordering to “opt out.” The study's main outcomes were 90-day mortality, discharge disposition, and increase in severity of stroke. Results were published online July 29, 2016, by the Journal of the American Heart Association.

The study included data on all patients 18 years of age or older who were admitted to any Kaiser Permanente Northern California hospital with a primary discharge diagnosis of ischemic stroke from July 2009 to September 2013. Patients were also required to have received neuroimaging during the hospitalization and at least one documented assessment of stroke severity according to the modified National Institutes of Health Stroke Scale within 24 hours of arrival, with a score of 1 or higher.

The EMR intervention took place in September 2011 and was done at all 20 hospitals at the same time without any specific communication to practicing physicians. Where previously physicians could sign a stroke order set without selecting an option in the statins section, the EMR change required them to first address the statins section by either ordering a statin or documenting why no statin was ordered.

The study included 6,131 hospitalizations for ischemic stroke during the study period—2,859 in the 26 months before the intervention and 3,272 in the 25 months afterward. After the EMR intervention, overall in-hospital statin administration increased from 87.2% to 90.7% (P<0.001) and early statin administration increased from 16.9% to 26.3% (P<0.001). Rate of survival at 90 days, meanwhile, showed a small increase associated with the EMR intervention in time-series modeling (88.4% vs. 88.9%), as did discharge to home or to a rehab facility (60.7% to 61.2%), while in-hospital neurologic worsening showed a small decrease (6.8% vs. 5.9%). Larger increases in rates of 90-day survival (87.2% vs. 94.1%) and discharge to home or rehab (57.8% to 72.1%) and a larger decrease in neurologic deterioration in the hospital (6.9% vs. 4.2%) were associated with an increase in early statin administration (i.e., within eight hours).

The authors noted that their analysis was retrospective and that the intervention was not assigned at random, among other limitations. However, they concluded that this multicenter EMR intervention was associated with increased early administration of statins after ischemic stroke, better rates of poststroke survival and discharge to rehab or home, and lower risk for in-hospital neurologic deterioration. “Simple interventions of this kind using a modern EMR represent an important new approach to examining the impact of prescribing changes on measurable clinical outcomes,” the authors concluded.