Recent Research

Autoimmune disorders and PE risk, perioperative therapy in patients with ICDs, and more.

Autoimmune disorders associated with high PE risk after hospital admission

Autoimmune disorders are associated with a high risk for pulmonary embolism (PE) up to a year after hospital admission, according to a recent study.

To determine whether autoimmune disorders conferred an excess risk for PE, researchers in Sweden examined data on persons who had not previously been admitted to the hospital for venous thromboembolism and who had received a primary or secondary diagnosis of an autoimmune disorder from Jan. 1, 1964 to Dec. 31, 2008. Data were obtained from a national database of all registered Swedish residents. The authors used the total Swedish population as a reference population and calculated adjusted standardized incidence ratios (SIR) for PE. The study results were published in the Jan. 21 The Lancet.

Over the study period, 535,538 patients were admitted to the hospital with an autoimmune disorder. Forty-seven percent were men, and 53% were women. In the first year after admission, the overall risk for PE was 6.38 times higher than in the general population. All types of autoimmune disorders studied were associated with increased risk, but the risk was particularly high for immune thrombocytopenic purpura, polyarteritis nodosa, polymyositis or dermatomyositis and systemic lupus erythematosus (10.79, 13.26, 16.44 and 10.23, respectively). The authors found that overall risk decreased over time since hospitalization (1.53 at one to five years, 1.15 at five to 10 years and 1.04 at 10 years or later). The increased risk for PE was observed in both men and women and for patients of all ages.

The authors noted that data were not available on cardiovascular risk factors, outpatient care, or any treatments received, among other limitations. However, they concluded that autoimmune disorders are not only inflammatory disorders but should be considered hypercoagulable disorders as well. “Prophylaxis could be warranted in patients admitted with autoimmune disorders or at least for those disorders for which the risk of pulmonary embolism was very high,” they wrote. They called for additional studies to determine the utility of such prophylaxis in this population.

One-fourth of ICD patients not receiving optimal medical therapy perioperatively

More than a quarter of eligible patients didn't receive optimal medical therapy for congestive heart failure at the time of implantable cardiac defibrillator (ICD) implantation, a recent analysis found.

Using the National Cardiovascular Data Registry, researchers examined data on 175,757 patients who underwent first ICD implantation at 1,201 centers between Jan. 1, 2007 and June 30, 2009. Patients were at least 18 years old, had a left ventricular ejection fraction (LVEF) of 35% or lower, and were stratified by use of perioperative optimal medical therapy (OMT). Researchers compared patients' clinical and procedural characteristics, as well as the characteristics of the physicians implanting the ICDs and the hospitals where the procedures were performed. Results were published in the Jan. 9 Archives of Internal Medicine.

Twenty-six percent (n=45,240) of the ICD recipients were eligible for OMT but didn't receive it. Rates were similar whether ICD placement was the primary purpose of hospitalization (24.6%) or whether the placement was for primary prevention (25.6%). Patients who did get OMT were more often younger, had hypertension, and had commercial insurance. They were less likely to have recently been hospitalized for heart failure, have a history of ischemic heart disease, or have renal dysfunction or atrioventricular node conduction abnormalities. Of patients who had coronary artery bypass graft surgery (CABG) while hospitalized (n=2,632), 65.7% were discharged on OMT, compared to 75.3% of patients (n=5,258) who underwent percutaneous coronary intervention (PCI) while hospitalized.

In multivariate analysis, higher OMT use was seen at teaching hospitals (odds ratio [OR], 1.16; 95% CI, 1.06 to 1.27) and with patients who had PCI during the admission (OR, 1.11; 95% CI, 1.04 to 1.19), a history of hypertension (OR, 1.32; 95% CI, 1.28 to 1.36), and a cardiovascular indication for admission (OR, 1.11; 95% CI, 1.04 to 1.19). Lower OMT use was seen with CABG during admission (OR, 0.66; 95% CI, 0.61 to 0.72), and an implanting physician who was board certified in surgery (OR, 0.73; 95% CI, 0.66 to 0.80). Lower OMT use was also seen in patients with medical comorbidities such as renal dysfunction and chronic lung disease and with more severe cardiovascular disease. Higher OMT rates were seen for implanting physicians with formal electrophysiology training.

The results suggest that an implanting physician's background may influence prescribing patterns and that patients whose ICDs were implanted by nonelectrophysiology clinicians should receive closer scrutiny, the authors said. Electronic decision support and standardized order sets may help with OMT guideline adherence, as may the direct involvement of a medical cardiologist in the peri-implantation setting, they wrote.

Limitations of the data registry used include that investigators didn't have information about antecedent and subsequent medication adherence or medication dosing, so the analysis provides a snapshot of medication use “at best,” an invited commentary author noted. Lower use of OMT by certain physician specialties is “interesting but to some degree a distraction,” as it's not clear the authors tested for covariate interactions, he added. More interesting is the finding that OMT was less common when an implant occurred during an admission that also included CABG, he said. “It is more than reasonable to inquire why a device implant occurs during a hospitalization for a revascularization procedure, which can lead to improvements in both ventricular function and the arrhythmia substrate, unless these device procedures were revisions rather than de novo implants. The latter are not recommended by current guidelines,” the commenter wrote.

C-reactive protein may predict outcomes after drug-eluting stents

C-reactive protein level (CRP) may predict long-term outcomes after implantation of a drug-eluting stent, a recent study indicates.

Researchers in Korea performed an analysis to determine the clinical utility of high on-treatment platelet reactivity (HTPR) testing and CRP level in predicting long-term outcomes of patients who had received drug-eluting stents and were taking clopidogrel. A total of 2,849 patients with drug-eluting stents received on-site platelet function testing to determine presence or absence of HTPR; of these, 2,546 also had data available on CRP level. A composite of all-cause death, nonfatal myocardial infarction, stent thrombosis and stroke was the primary end point. The study results were published in the Dec. 13/20, 2011 Journal of the American College of Cardiology.

The patients had a mean age of 61.7 years, and most (71.1%) were men. More than half (58.3%) were found to have HTPR. At two years of follow-up, patients with and without HTPR did not differ in occurrence of the primary end point (2.8% vs. 2.4%; P=0.18), while patients with high CRP levels were at higher risk than those whose levels were normal (5.6% vs. 1.7%; P<0.001). Platelet function testing did not appear to be clinically useful in predicting long-term outcomes, but adding CRP level to a model that included other conventional risk factors did appear to improve risk prediction (C-statistic, 0.729 to 0.759; P=0.03).

The authors pointed out that their study was observational and used nonrandomized data, that only one type of platelet function test was used, and that the overall event rate was low, among other limitations. However, they concluded that although HTPR as measured in their study had no predictive value in patients with drug-eluting stents, high CRP levels predicted worse outcomes and may help stratify risk in this population.

The authors of an accompanying commentary noted that the study results could hold promise for personalized therapy in patients who receive drug-eluting stents. “Integrating the current evidence and practice guidelines, genetic and platelet function testing are suggested in selected patients that would benefit the most from testing,” the commentary authors wrote. “This patient group is still being defined, but might include patients with prior stent thrombosis, obese or very low body weight individuals, and (incorporating the current study's results) patients with CRP ≥3 mg/L.”

Thrombolysis may benefit acute ischemic stroke patients with diabetes and prior stroke

Thrombolysis appeared to benefit patients with acute ischemic stroke who had concomitant diabetes or a history of stroke, according to a recent study.

Guidelines in the U.S. and Europe have recommended that recombinant tissue plasminogen activator (rtPA) not be used in patients with diabetes or with prior stroke, although this is an area of some debate and these recommendations are not always followed in clinical practice. European researchers compared registry data to determine how diabetes and prior stroke affected outcomes of patients with acute ischemic stroke who received thrombolysis versus controls who did not. Ninety-day modified Rankin Scale scores were compared after adjustment for age and National Institutes of Health Stroke Scale (NIHSS) score at baseline. The study results were published in the Nov. 22, 2011 Neurology.

Overall, data were available for 29,500 patients, 5,411 (18.5%) with diabetes, 5,019 (17.1%) with prior stroke and 1,141 (5.5%) with both. Adjusted modified Rankin Scale scores were better in treated patients than controls among those with diabetes, stroke, or both (odds ratios, 1.45, 1.55, and 1.23; P<0001 for all comparisons according to the Cochran-Mantel-Haenszel test). These results were similar to the 19,939 patients without diabetes or prior stroke, whose odds ratio for the adjusted modified Rankin Scale score was 1.53 (P<0.0001) for the comparison between treated patients and controls. Patient age (≤80 years or >80 years) did not affect outcomes.

The authors acknowledged that the data used in their study were not randomized but concluded that patients who received thrombolysis for acute ischemic stroke had better outcomes, even if they had diabetes or prior stroke, than those who did not receive the therapy. The researchers did not see a significant benefit in patients with both conditions but noted that the subgroup of these patients was small and that no interaction was observed between diabetes and prior stroke and treatment effect. Because the observed benefit of therapy in their study was similar to that seen in patients without diabetes and prior stroke, the authors concluded that there is no reason to withhold rtPA for acute ischemic stroke in patients with these conditions.

The author of an accompanying editorial reiterated the variety of opinions in this area, noting that clinicians have had many questions about how and whether recommendations about eligibility for thrombolysis should be followed. He called the current study “a concerted empirical effort” to determine whether such recommendations are valid for the significant number of patients—up to 15%—who present to the emergency department with a history of prior stroke and diabetes. “There appears to be no justification for the continued restriction of these patients from thrombolytic therapy,” the editorialist concluded.

Two-thirds of adverse drug event hospitalizations in elderly linked to four drug classes

Just four drug classes were involved in more than two-thirds of the hospitalizations of older patients for adverse drug events from 2007 through 2009, a recent analysis found.

Researchers used 2007-2009 data from the 58 hospitals that participate in the National Electronic Injury Surveillance System-Cooperative Adverse Drug Event Surveillance (NEISS-CADES) project to estimate the frequency and rate of emergency hospitalizations of adults aged 65 years and older. They also looked at the roles of specific medications in the hospitalizations, such as drugs designated as high-risk in the elderly by the 2011 Healthcare Effectiveness Data and Information Set (HEDIS) or as “potentially inappropriate” for use in older adults by the updated Beers criteria. Included cases involved hospitalizations for conditions that a clinician expressly attributed to use of a drug, or to a drug-specific adverse effect. Prescription and over-the-counter drugs, vaccines and dietary supplements were included in the analysis. Results were published in the Nov. 24, 2011 New England Journal of Medicine.

On the basis of 5,077 cases in the researchers' sample, they estimated that 99,628 elderly patients had emergency hospitalizations for adverse drug events. Four types of medication, taken alone or in combination, were linked to 67% of the cases: warfarin (33.3%), insulin (13.9%), oral antiplatelets (13.3%) and oral hypoglycemics (10.7%). Most hospitalizations involving warfarin (95.1%), insulin (99.4%) or oral hypoglycemics (99.1%) came from unintentional overdoses. Of hospitalizations attributed to warfarin, a second medication was implicated in 12.5% of visits, most commonly an antiplatelet (6.7%); of hospitalizations attributed to insulin, another medication was implicated in 15.4% of visits, most commonly an oral hypoglycemic (10.1%).

Medications dubbed high-risk by HEDIS were involved in just 1.2% of hospitalizations, while those dubbed potentially inappropriate by Beers criteria were involved in 6.6%. Forty-eight percent of adverse events involved patients aged 80 years or older, and the hospitalization rate was 3.5 times for adults aged 85 years or older vs. those aged 65 to 69 years. Sixty-six percent of the hospitalizations were due to unintentional overdoses.

The analysis probably underestimated the number of emergency hospitalizations, the authors said, because NEISS-CADES data rely on emergency doctors' identification and documentation of adverse drug events, thus events confirmed during hospitalization or by patient interviews aren't likely to be captured. Overall, efforts to improve medication safety in older adults should focus on areas likely to yield the largest and most measurable and clinically significant effects, such as management of antithrombotics and diabetes drugs, they said.

Corticosteroids beneficial in patients with COPD exacerbations on ventilatory support

Systemic corticosteroids may increase the success of noninvasive mechanical ventilation and reduce the duration of mechanical ventilation in patients with acute exacerbations of chronic obstructive pulmonary disease (AECOPDs), recent research suggests.

Researchers ran a double-blind, placebo-controlled, randomized trial to test the safety and efficacy of systemic corticosteroid treatment in patients on ventilatory support (invasive or noninvasive) who had a COPD exacerbation. They screened 354 adult ICU patients from eight hospitals in four countries from July 2005 through July 2009, and excluded 271, usually for prior use of corticosteroids. The remaining 83 patients were randomized to receive intravenous methylprednisolone (0.5 mg/kg every 6 hours for 72 hours, 0.5 mg/kg every 12 hours on days 4 through 6, and 0.5 mg/kg/d on days 7 through 10) or placebo. The groups didn't differ in demographics, illness severity, reason for COPD exacerbation and gas exchange variables, though the blood glucose level was higher (P=0.02) in the corticosteroids group, probably due to a higher prevalence of diabetes in this group. Results were published in the Nov. 28, 2011 Archives of Internal Medicine.

Corticosteroid treatment was associated with a one-day reduction in the median duration of mechanical ventilation (MV) (3 days vs. 4 days; P=0.04) and a trend toward a shorter length of stay in the ICU (6 days vs. 7 days; P=0.09). Also, the rate of noninvasive mechanical ventilation (NIV) failure—and thus rescue MV—was dramatically reduced in patients who received corticosteroid treatment (0% vs. 37%; P=0.004). Mortality in the ICU was similar in both groups. Corticosteroid treatment was associated with a rise in the risk of hyperglycemia requiring treatment (46% vs 25%; P=0.04)—a known side effect. The corticosteroid group had significantly higher glucose levels and daily insulin doses during the five-day study period.

The study results offer strong evidence that systemic corticosteroids can benefit patients who aren't usually included in clinical trials—those on MV and/or requiring ICU admission, the authors wrote. The avoidance of tracheal intubation (a byproduct of the corticosteroid therapy) was the likely reason for the shorter duration of MV and shorter length of stay in the NIV group, they added. Further, these results may be generalized because the characteristics of the patients and the outcomes were consistent with other (observational) studies. The optimal dose of corticosteroids and the duration of treatment for exacerbations that require hospitalizations are still unknown, however, they said.

Invited commenters said the results are “certainly clinically significant,” as well as economically important. “Given the economic burden of AECOPDs, reducing both ICU length of stay and the need for rescue MV can lead to substantial savings,” they wrote. They did raise concerns about study methodology, however, such as whether the investigators were truly blinded, the fact that study enrollment was less than 25% of the planned sample size, and that equipoise (the concept that there must be uncertainty as to the benefit of the intervention under study) “was at least potentially in question for the current trial.”

New-onset afib in severe sepsis associated with stroke, death risk

Severe sepsis patients with new-onset atrial fibrillation (AF) had a higher risk of in-hospital stroke and death compared to those without AF or with preexisting AF.

Researchers used 2007 discharge data on 49,082 adults with severe sepsis from the California State Inpatient Database, which comprises data from all patients hospitalized in nonfederal acute care hospitals in California. The mean patient age was 69 years. After excluding AF cases present at admission, new-onset AF was defined as AF or atrial flutter that occurred during the hospital stay. Severe sepsis, AF and ischemic stroke were defined by the presence of the ICD-9-CM codes for those conditions. Results were published online Nov. 13, 2011 in the Journal of the American Medical Association.

Inpatients with severe sepsis had a significantly higher risk of new-onset AF compared to inpatients without severe sepsis (adjusted odds ratio [OR], 6.82; 95% CI, 6.54 to 7.11; P<0.001). Severe sepsis patients with new-onset AF had higher risks of in-hospital stroke compared to severe sepsis patients without new-onset AF (2.6% vs. 0.6% strokes; adjusted OR, 2.70; 95% CI, 2.05 to 3.57; P<0.001). The former also had a higher risk of in-hospital death (56% vs. 39% deaths; adjusted relative risk, 1.07; 95% CI, 1.04 to 1.11; P<0.001). Within the group of severe sepsis patients without new-onset AF, those with preexisting AF had a 0.57% risk of in-hospital ischemic stroke and a 44% risk of death, while those without any AF had a 0.69% risk of stroke and a 38% risk of death. The increased stroke and mortality risks seen with new-onset AF “were robust across two definitions of severe sepsis, multiple methods of addressing confounding, and multiple sensitivity analyses,” the authors noted.

Current guidelines don't address AF that occurs in the setting of severe sepsis or acute infection, which suggests that new-onset AF in this setting “is an underrecognized public health problem,” the authors wrote. It's projected that one million Americans will have severe sepsis in 2011; this study suggests more than 60,000 Americans will also have new-onset AF and the associated risks of ischemic stroke and in-hospital death. If these findings are replicated, “it will be important to examine management strategies that might diminish the risk of adverse outcomes associated with AF during severe sepsis,” the authors concluded.

Tool helps stratify risk of patients with acute COPD exacerbations

Researchers successfully validated a tool that helps stratify risk of in-hospital death and mechanical ventilation in patients with acute exacerbations of chronic obstructive pulmonary disease (AECOPD) at the time they present to the hospital.

Using 2007 data from a clinical research database, researchers analyzed 34,699 admissions to 177 U.S. hospitals of patients older than age 40 years with a principal diagnosis of AECOPD (81%) or acute respiratory failure with a secondary diagnosis of AECOPD (19%). Based on information available at hospital presentation, patients were put into one of five classes of the BAP-65 tool (BAP-65 criteria are blood urea nitrogen [BUN] ≥25 mg/dL, altered mental status, pulse >109 beats/min, and age >65 years). Patients with none of the first three criteria who were age 65 or younger were class I; those with no criteria who were older than age 65 were class II. Patients with one, two or three risk factors were class III, IV and V, respectively. Primary end points were hospital mortality and need for mechanical ventilation, while secondary end points were length of stay (LOS) and costs. Results were published in the November 2011 Chest.

Mortality rates increased with rising BAP-65 class, from fewer than 1% of patients in class I to more than 25% of patients in class V (P<0.001). Need for mechanical ventilation also increased with class, from 2% in class I to 55% in class V (P<0.001). The area under the receiver-operating characteristic curve (AUROC) for BAP-65 for hospital mortality and/or need for mechanical ventilation was 0.79 (95% CI, 0.78 to 0.80). While the median LOS was four days, median LOS was only three days in class I patients and rose almost linearly to seven days in class V patients (P<0.001). Likewise, median costs for class I patients were $4,307 and rose to $11,473 for class V patients (P<0.001).

The current analysis expands on initial work on the BAP-65 tool by validating it in a large group of patients distinct from those in which it was developed, by including a population that had previously been excluded (those with a principal diagnosis of respiratory failure), and by measuring resource use (LOS and costs), the authors noted. An advantage of the BAP-65 is its objectivity, which means it can be applied with consistency, reliability and generalizability, the researchers concluded, while its information on LOS and cost can be used for economic risk stratification.