Recent Research

Blood pressure after stroke, mortality risk prediction, and more.

Lowering blood pressure immediately after stroke doesn't reduce death, disability

Using medication to lower blood pressure in the first 48 hours after acute ischemic stroke onset doesn't reduce death or disability, a recent study found.

Researchers recruited 4,071 stroke patients from 26 hospitals across China between August 2009 and May 2013. Patients were randomized either to discontinue all antihypertensive medications during hospitalization or to get antihypertensive treatment. The treatment aimed to lower systolic blood pressure by 10% to 25% within the first 24 hours after randomization, to achieve blood pressure less than 140/90 mm Hg within 7 days, and to maintain that level through the remainder of the hospitalization. Several types of antihypertensives were used, individually and in combination, to achieve the goals. The main, combined outcome was death and major disability, defined by a modified Rankin score ≥3 at 14 days or at hospital discharge.

Though mean systolic blood pressure was significantly reduced in the treatment versus the control group, the main outcome didn't differ between groups (683 events with treatment vs. 681 events without). Treatment-group patients saw mean systolic blood pressure drop to 144.7 mm Hg from 166.7 mm Hg within 24 hours, compared to a drop from 165.6 mm Hg to 152.9 mm Hg in the control group (P<0.001). Blood pressure remained significantly lower in the treatment group at 3-month follow-up despite the majority of patients in each group being on antihypertensives (84.5% of the treatment group vs 75.4% of the control group). However, death and disability didn't differ significantly between groups, and neither did vascular events or recurrent stroke, although recurrent strokes were slightly reduced. Results were published in the Feb. 5 Journal of the American Medical Association.

Study limitations include that patients with a blood pressure ≥220/120 mm Hg were excluded, as were patients who had received intravenous thrombolytic therapy for their stroke. Also, Chinese patients may not be representative of Western patients; they are more likely to use heparin, for example, the researchers noted. Still, past research has shown the association between blood pressure and stroke is similar between Chinese and Western populations, they added. The decision to lower blood pressure in acute ischemic stroke patients should be based on clinical judgment, the authors concluded.

Tool helps predict 1-year death risk at admission

Researchers have validated a prognostic tool that can be used at admission to estimate a patient's risk of dying within a year.

In a retrospective, observational, cohort study, researchers tested their prognostic tool on 1,064 patients admitted to medical and surgical inpatient services between July and August 2005. Patients came from 1 university hospital and 1 safety-net hospital in Colorado. The researchers sought to validate their index, which had previously been tested successfully in a Veterans Administration hospital. The CARING index comprises primary diagnosis of Cancer, ≥2 Admissions to the hospital for a chronic illness within the last year; Resident in a nursing home; ICU admission with multiorgan failure; and Non-cancer hospice Guidelines. The study's primary end point was death at 1 year. Results were published in the December 2013 Journal of Hospital Medicine.

Thirty-seven percent of the patients met at least 1 of the CARING criteria, and 12.6% died within a year of the index hospitalization. One-year survival was significantly lower for those who met at least 1 of the CARING criteria. The following were individually predictive of 1-year mortality: primary diagnosis of cancer (odds ratio [OR], 7.23), ICU admission with multiple organ failure (OR, 6.97), >2 noncancer hospice guidelines (OR, 15.55), and age (OR, 1.60). Neither being admitted to the hospital at least twice, nor being a resident in a nursing home, was predictive of mortality.

The CARING criteria can be applied to patients quickly and easily, in order to identify those who might benefit from palliative interventions and consults, the authors wrote. Hospitalists, in particular, are a good target for the criteria since they are often first-line clinicians in the hospital, they added.

Pneumonia after acute stroke is associated with other medical complications

Pneumonia after acute stroke is associated with several other kinds of inpatient medical complications, a recent study found.

Researchers sought to define the interrelationship of medical complications after stroke. They analyzed patients enrolled in the China National Stroke Registry from 2007 to 2008, 14,702 of whom had acute ischemic stroke (AIS) and 5,221 of whom had intracerebral hemorrhage (ICH). They sought information on the following in-hospital complications after stroke: recurrent stroke, epileptic seizure, hydrocephalus, myocardial infarction, atrial fibrillation/flutter, pneumonia, urinary tract infection (UTI), gastrointestinal bleeding, deep venous thrombosis, pulmonary embolism and decubitus ulcer. Results were published in the December 2013 Stroke.

Pneumonia was the most common complication after AIS (11.4%) and ICH (16.8%). In both groups of patients, pneumonia was significantly associated with development of gastrointestinal bleeding, decubitus ulcer, deep venous thrombosis, epileptic seizure, UTI, atrial fibrillation/flutter and recurrent stroke (P<0.001 for all). A significant association was also found between several of the nonpneumonia complications after stroke, though once the data were adjusted for pneumonia, these associations were reduced, especially for pairs involving UTI, atrial fibrillation/flutter and gastrointestinal bleeding.

The findings indicate that pneumonia might be a risk factor or marker for developing several other medical complications after acute stroke, the researchers wrote. The results also suggest that association between nonpneumonia complications after acute stroke might be mediated by pneumonia, they said.

Therapeutic hypothermia didn't improve outcomes for cardiac arrest patients

Lowering the temperature of cardiac arrest patients to 33 °C did not increase their survival compared to targeting a temperature of 36 °C, a recent study found.

This multisite, international trial included 939 adults who were unconscious after out-of-hospital cardiac arrest of presumed cardiac cause. They were randomized to management with a targeted temperature of either 33 °C or 36 °C and followed for 180 days. Results were published in the Dec. 5, 2013, New England Journal of Medicine.

At the end of the trial, which included 28 hours of cooling followed by 8 hours of gradual re-warming, 50% of the patients in the lower-temperature group had died compared with 48% in the higher-temperature group (hazard ratio [HR], 1.06; 95% CI, 0.89 to 1.28). The groups also had similar rates of the study's combined secondary outcome, measured at 180 days: poor neurologic function (according to the Cerebral Performance Category scale) or death (54% of the 33 °C patients vs. 52% of the 36 °C patients; HR, 1.02; 95% CI, 0.88 to 1.16).

A target temperature of 33 °C provided neither benefit nor harm for these patients compared to a target of 36 °C, the researchers concluded. The results may appear to conflict with the initial research that motivated guidelines favoring therapeutic hypothermia, but there are a number of important differences, they noted.

This study was larger than the previous ones and had a broader range of patients, including those with nonshockable rhythms, which could suggest that hypothermia has varying effects on different subgroups of patients. Also, this trial controlled all patients' body temperatures, so it may be that preventing fever by using the target of 36 °C was sufficient to provide benefit. Based on these results, “decisions about which temperature to target after out-of-hospital cardiac arrest require careful consideration,” the authors concluded.

An accompanying editorial observed that the study reflected the great improvement that has occurred in survival rates for these patients during the past decade and that “it seems clear we should not regress to a 2002 style of care that does not manage temperature at all.”

Simple screening tool assesses frailty in elderly patients with acute coronary syndrome

The highest category score for the Edmonton Frail Scale (EFS) in elderly patients with acute coronary syndrome was associated with increased comorbidity, longer lengths of stay, and fewer procedures, and was independently associated with mortality, a study found.

The Edmonton Frail Scale is a user-friendly screening interview that requires less than 5 minutes to administer and was designed for non-geriatricians. The scale is derived from 9 factors: cognition (drawing a clock diagram); general health status (hospital admissions and a general description); functional independence (activities of daily living); social support (individuals who can help); medication use (5 or more prescriptions, remembering to take them); nutrition (weight loss); mood (sadness or depression); unexpected urinary incontinence; and functional performance on the timed get up and go test.

Scores range from 0 (not frail) to 17 (very frail). Researchers seeking to assess its use in acute coronary syndrome administered it as part of a pilot study of 183 consecutive patients 65 years or older who were admitted to a single center in Edmonton, Alberta, Canada. Frailty was defined as weight loss, fatigue, and weakness or a state of vulnerability arising from biological, cognitive and social factors. Results appeared in the December 2013 Canadian Journal of Cardiology.

Patient scores ranged from 0 to 13. Patients with higher scores were older, with more comorbidities, longer lengths of stay (EFS 0 to 3: mean, 7.0 days; EFS 4 to 6: mean, 9.7 days; and EFS ≥7: mean, 12.7 days; P=0.03), and decreased procedure use. Crude mortality rates at 1 year were 1.6% for EFS 0 to 3, 7.7% for EFS 4 to 6, and 12.7% for EFS ≥7 (P=0.05).

After adjusting for baseline risk differences using a “burden of illness” score, the hazard ratio for mortality for EFS ≥7 compared with EFS 0 to 3 was 3.49 (95% CI, 1.08 to 7.61; P=0.002).

Researchers noted the advantages and disadvantages of simple screening tools in the context of frailty. The complexity of some other methods makes simple tools attractive to clinicians, they wrote. Even if some nuances are lost, simple tools can still be predictive. And, the EFS has been validated in multiple settings. Still, the authors noted that this was a pilot study designed to assess the tool's use in acute coronary syndrome. Researchers wrote, “Further work is needed to determine whether the use of a validated frailty instrument to better delineate some of the ‘unmeasured factors' involved in medical decision making in elderly patients with cardiovascular disease would provide more transparent and refined discussions of risk and the opportunity for interventions to improve this risk in this important, often disadvantaged, population.”

Perioperative beta-blockers may help some, not all, noncardiac surgery patients with ischemic heart disease

In patients with ischemic heart disease having noncardiac surgery, perioperative beta-blockers appear to improve outcomes only in cases of concurrent heart failure or recent myocardial infarction (MI), according to a recent study.

Researchers in Denmark identified patients in nationwide registries who had ischemic heart disease with or without heart failure and with or without a history of MI and who underwent noncardiac surgery between Oct. 24, 2004, and Dec. 31, 2009. The study's objective was to determine whether beta-blockers were associated with major adverse cardiovascular events (MACEs) and all-cause mortality in this population. Main outcome measures were 30-day risk of MACE, defined as ischemic stroke, acute MI, or cardiovascular death, and all-cause mortality. The results were published online Nov. 18, 2013, by JAMA Internal Medicine.

The study included 28,263 patients with ischemic heart disease who were having noncardiac surgery, 7,990 (28.3%) with heart failure and 20,273 (71.1%) without. MACE occurred in 1,374 of all patients (4.9%), and 1,773 of all patients died (6.3%). Patients with heart failure were significantly more likely to have adverse events than those without heart failure. A total of 4,262 patients with heart failure (53.5%) and 7,419 without heart failure (36.6%) received beta-blockers.

Overall hazard ratios (HRs) associated with beta-blockers were 0.90 (95% CI, 0.79 to 1.02) for MACE and 0.95 (95% CI, 0.85 to 1.06) for all-cause mortality. Patients with heart failure had a significantly lower risk for MACE on beta-blockers (HR, 0.75; 95% CI, 0.70 to 0.87), while among those without heart failure, MACE (HR, 1.11; 95% CI, 0.92 to 1.33) and all-cause mortality (HR, 1.15; 95% CI, 0.98 to 1.35) did not appear to be associated with beta-blocker use. Patients without heart failure who had had an MI within 2 years also appeared to benefit from beta-blockers (HRs, 0.54 for MACE [95% CI, 0.37 to 0.78] and 0.80 for all-cause mortality [95% CI, 0.53 to 1.21]).

The researchers noted that beta-blocker use was determined by outpatient prescriptions rather than hospital data and that information on indications for beta-blocker treatment, doses, and patient adherence were not available, among other limitations. However, they concluded that perioperative use of beta-blockers with noncardiac surgery in patients with ischemic heart disease and heart failure or a recent MI appears to be associated with decreased risk for MACE and all-cause mortality 30 days postoperatively.

The authors of an accompanying editorial congratulated the researchers on their study and said that its results can help inform current clinical practice, although a larger randomized clinical trial remains necessary. The current study, they wrote, questions the conventional wisdom that perioperative beta-blocker therapy should be universal.

“Instead, the astute clinician may need to exercise more judgment in selectively prescribing these medications,” the editorialists wrote. “In the end, we should not be too surprised that even something as instinctive and habitual as perioperative β-blocker therapy for patients with ischemic heart disease must be prescribed in a judicious and personalized manner.”

Thyroid hormones may be associated with mortality in elderly inpatients

Results of thyroid function tests may be associated with mortality in elderly hospitalized patients, according to a recent study.

Researchers in Spain performed a 7-year prospective observational study to examine the relationship between results of thyroid function tests during hospitalization and all-cause and cardiovascular mortality in elderly inpatients. Levels of thyroid-stimulating hormone (TSH), free T4 (FT4), and free T3 (FT3) were measured during the first day of admission, and all-cause and cardiovascular mortality were assessed during follow-up until Jan. 1, 2012. All patients taking medications known to modify thyroid function were excluded. The study results were published in the December 2013 Journal of Clinical Endocrinology and Metabolism.

A total of 404 patients over 65 years of age who were admitted to the geriatrics department at a single hospital in 2005 were included in the study. Two hundred forty-seven were women, and 157 were men. Most patients (73%) had abnormal results on thyroid function tests at admission, with non-thyroidal illness syndrome being the most common alteration (62.1% of the study patients). Three hundred twenty-three patients (80%) died during the study, 61 of them during hospitalization; the median survival time for all patients was 9 months (interquartile range, 1 to 31 months).

In Kaplan-Meier analysis, patients in the first (lowest) tertile of serum FT3, TSH, and serum FT4 had significantly shorter median survival time for all-cause mortality. In multivariate-adjusted Cox regression analysis, history of cancer, age and levels of FT3 were significantly related to all-cause mortality (hazard ratios, 1.60 [P=0.009], 1.03 [P=0.003] and 0.72 [P<0.001], respectively). In the 202 patients for whom cause of death was known, 61 (30.2%) died of cardiovascular disease, most commonly those in the first tertile of TSH and FT3. Free T3, cancer and age were found to be significant predictors of cardiovascular death in adjusted Cox regression analysis (hazard ratios, 0.76 [P=0.004], 1.64 [P=0.027] and 1.05 [P=0.003], respectively).

The authors noted that their results on cardiovascular mortality are limited by selection bias because data on cause of death were not available for all patients. However, they concluded that results of thyroid function tests are related to mortality in elderly patients during hospitalization and in the long term after hospital discharge. “Low FT3, low FT4, and low TSH serum concentrations are associated with decrease[d] survival time, although only low FT3 behaves as a significant predictor of all-cause and [cardiovascular] mortality,” they wrote.

Apixaban as safe as warfarin before cardioversion for atrial fibrillation

In atrial fibrillation patients, apixaban before cardioversion appears to be as safe as warfarin, a recent study found.

In a post-hoc analysis of the ARISTOTLE study, researchers studied 743 cardioversions in 540 patients. Eligible patients had documented atrial fibrillation (AF). They also had at least 1 stroke risk factor. Patients were randomized to receive either warfarin, adjusted to a target international normalized ratio (INR) of 2.0 to 3.0, or apixaban in doses of either 5 mg twice daily or 2.5 mg twice daily, depending on age, weight, and kidney function. The study's main efficacy outcome was stroke and the main safety outcome was major bleeding. Secondary end points were death or myocardial infarction (MI). Patients were followed for 30 days after cardioversion.

Seventy-five percent of cardioversions occurred within 1 year. The mean time to the first cardioversion for patients assigned to apixaban was 251±248 days, while for warfarin patients it was 243±231 days. No cardioversion patients had a stroke or systemic emboli during 30-day follow-up. In each of the warfarin and apixaban groups, 1 patient had an MI, 1 had major bleeding (0.2%) and 2 died. Results were published in the November 2013 Journal of the American College of Cardiology.

Clinical events after cardioversion of AF are comparable for apixaban and warfarin patients, the researchers concluded. Since effective anticoagulation is achieved more quickly with newer oral anticoagulants than warfarin, these newer drugs may shorten pretreatment time before cardioversion, the authors wrote. They cautioned, though, that the minimum duration of newer anticoagulants to assure low risk of an embolic event hasn't been determined, and most ARISTOTLE patients received cardioversion after months of anticoagulation. “Until additional data are reported, elective cardioversion of AF could be performed with a low risk of stroke or systemic emboli in patients treated chronically with new oral anticoagulants,” the researchers wrote.

Pregnant women admitted to hospital for reasons unrelated to delivery have higher risk of first venous thromboembolism

Pregnant women who are admitted to the hospital for reasons not related to delivery have a higher risk of first venous thromboembolism, a recent study found.

In a retrospective cohort study, U.K. researchers used a national database to examine patient records of 206,785 English women who had 1 or more pregnancies between 1997 and 2010. Within this group, they retrieved information on admissions that lasted at least 1 day, except when the cause of admission was delivery or venous thromboembolism (VTE). The main outcome measure, risk of first VTE, was assessed by calculating the absolute rate of VTE in women who were admitted during pregnancy, and comparing them with VTE rates of pregnant women who weren't admitted. Results were published online Nov. 7, 2013, by BMJ.

About 18% of pregnancies (42,256 pregnancies) included at least 1 admission prior to the delivery admission, and 4.7% of women were admitted more than once.

Women admitted to the hospital during pregnancy had a VTE risk 17 times higher during the admission than women who didn't go to the hospital (absolute rate [AR] 1,752/100,000 person-years; incidence rate ratio [IRR], 17.5). The VTE rate at 28 days post-discharge was 6 times higher for women who were admitted, as well (absolute rate [AR] 676/100,000 person-years; IRR, 6.27), with the rate highest in the first 2 weeks post-discharge.

The combined VTE rate during and 28 days post-discharge was highest in the third trimester and in those at least 35 years of age. Combined VTE risk was fourfold higher for those admitted for less than 3 days (AR, 558/100,000 person-years; IRR, 4.05), and 12 times higher for those admitted for 3 days or longer (AR, 1,511/100,000 person-years; IRR, 12.2).

The results suggest that clinicians need to carefully consider which women should receive prophylaxis during a pre-delivery admission, and for how long, the authors wrote. In particular, the results merit “prudent consideration” of pregnant women during the 28 days following hospital discharge (for a pre-delivery admission), they wrote.

As well, while some guidelines suggest prophylaxis for women admitted to the hospital only if she has certain risk factors (like obesity), this study indicated there is a significantly elevated risk in women who lack these risk factors, they wrote. However, the authors noted that the benefits of prophylaxis need to be weighed against the risk of major hemorrhage.

These summaries come from ACP HospitalistWeekly, an e-newsletter provided every Wednesday by ACP Hospitalist. To receive it, call Customer Service at 800-543-1546, ext. 2600, or direct at 215-351-2600 (M-F, 9 a.m. to 5 p.m. EST); send an email; or subscribe online.