Literature at a Glance
A guide to this month’s studies.
- Carotid stenting is equivalent to endarterectomy in carotid artery stenosis.
- Idiopathic ventricular fibrillation is associated with early repolarization.
- Aggressive LDL and blood pressure management may benefit diabetic patients.
- Treatment of hypertension in patients older than age 80 improves outcomes.
- Length of stay predicts mortality in pulmonary embolism patients.
- Poor symptom control and lack of family support during end-of-life hospital stays.
- Potentially inappropriate medication use in hospitalized elders is common.
- Steroids may not help in pediatric meningitis.
- PCI and CABG may be equivalent in the treatment of left main disease.
Background: Patients with moderate to severe symptomatic carotid artery stenosis and those with severe asymptomatic carotid stenosis benefit from carotid endarterectomy. Carotid stenting may provide an alternative therapy, but the long-term protection against stroke compared with endarterectomy is unclear.
Study Design: Prospective randomized trial.
Setting: 29 centers in the United States.
Synopsis: This article reports the long-term (three years) follow-up of the SAPPHIRE trial, published in 2004, which compared carotid stenting to endarterectomy in patients at high surgical risk. In that trial, 334 patients randomized to either stenting or endarterectomy had similar outcomes at one year. Patients were followed for three years with death and major cardiovascular events as endpoints.
Rates of stroke at three years were approximately 10% with an overall death rate of approximately 20%. There was no difference between carotid stenting and endarterectomy with regards to death, stroke, or other cardiovascular outcome.
Notably, follow-up was not complete (78%), a specific type of stenting procedure was used, and the patient population was at high risk for surgical complications. Therefore, results may not be applicable in other centers or in other patient populations. Yet, this trial provides follow-up, long-term evidence that carotid stenting may be a viable alternative to endarterectomy in patients with carotid artery stenosis.
Bottom line: Carotid stenting and endarterectomy had similar outcomes at three years in high-risk patients with carotid artery stenosis.
Citation: Gurm HS, Yadav JS, Fayad P, et al. Long-term results of carotid stenting versus endarterectomy in high-risk patients. N Engl J Med. 2008;358:1572-1579.
Background: Electrocardiographic early repolarization, defined as elevation of the QRS-ST junction of at least 0.1mV from baseline in the inferior or lateral leads (manifested as slurring or notching), occurs in 1% to 5% of patients. It is considered benign, but experimental studies have suggested it may be arrhythmogenic.
Study Design: Prospective case-control.
Setting: 22 international tertiary care centers.
Synopsis: Case subjects were less than 60 years of age and were resuscitated after ventricular fibrillation (VF) arrest ultimately deemed idiopathic. All had normal echocardiograms, no evidence of coronary artery disease, and no repolarization abnormalities (including Brugada and long-QT). Of 206 patients, 31% had early repolarization on EKG, versus only 5% in controls without heart disease. In case subjects with prior EKGs, early repolarization was proven to be pre-existing.
The mean magnitude of J-point elevation was 2 mm in cases versus 1.2 mm in controls, and in cases this magnitude increased during later episodes of arrhythmia. Electrophysiologic mapping showed that ectopy originated at sites concordant with the location of abnormal repolarization. During five years of follow-up, arrhythmic recurrence was twice as common in cases with early repolarization.
Although long-term observational studies of persons with early repolarization have shown a benign natural course, this study may change our approach to those with syncope or a family history of sudden death.
Bottom line: Early repolarization on EKG is associated with idiopathic ventricular fibrillation.
Citation: Haissaguerre M, Derval N, Sacher F, et al. Sudden cardiac arrest associated with early repolarization. N Engl J Med. 2008;358(19):2016-2023.
Does Aggressive Blood Pressure and LDL Treatment in Diabetics Affect Development of Subclinical Atherosclerosis?
Background: There is evidence to suggest more aggressive treatment of LDL cholesterol in patients with known coronary artery disease is beneficial and more aggressive blood pressure control can improve outcomes in some patient populations. However, it is unclear if patients with diabetes without cardiovascular disease would benefit from more aggressive LDL and systolic blood pressure (SBP) treatment.
Study Design: Randomized, open-label, blinded-to-end point trial.
Setting: Four centers in Oklahoma, Arizona, and South Dakota.
Synopsis: Investigators studied 499 type 2 diabetic American Indian men with no history of cardiovascular disease. Patients were randomized to receive treatment to achieve aggressive (70 mg/dL and 115 mmHg) or standard (100 mg/dL and 130 mmHg) targets for their LDL cholesterol and SBP, respectively.
At three years, the aggressive group showed decreased carotid intima-media thickness (IMT) and decreased left ventricular mass, whereas both IMT and left ventricular volume increased in the standard group. There were no differences in clinical cardiovascular events between the aggressive and standard group and both groups had lower-than-expected clinical events.
This study included no women and was limited to an American Indian population. Of note, there was an increase in adverse events related to blood pressure medications in the aggressive group. It also is unclear how the surrogates of cardiovascular disease or subclinical atherosclerosis relate to significant clinical outcomes.
Bottom line: More aggressive LDL and SBP treatment in diabetics without coronary disease decreased subclinical atherosclerosis but did not impact clinical outcomes.
Citation: Howard B, Roman M, Devereux R, et al. Effect of lower targets for blood pressure and LDL cholesterol on atherosclerosis in diabetes. JAMA. 2008;299(14):1678-1689.
Background: There is debate about whether treatment of hypertension in the elderly is beneficial. Numerous studies suggest blood pressure control does less to prevent strokes in patients older than 80 years than for younger patients. Moreover, other evidence shows controlling blood pressure in elderly patients may result in an increase in mortality even if there was a decreased risk of stroke.
Study Design: Randomized, double-blind, placebo-controlled trial.
Setting: 195 centers in 13 countries in Europe, China, Australasia, and North Africa.
Synopsis: This study evaluated 3,845 patients, age 80 or older, with a sustained systolic blood pressure (SBP) of 160 mmHg and randomized them to receive indapamide (sustained release) or placebo. Perindopril, or placebo, was added if necessary to achieve a target blood pressure of 150/80 mmHg. Patients who received the indapamide with or without the perindopril had lower blood pressure, lower rate of stroke, lower rate of heart failure, lower rate of death from a cardiovascular cause, and a 21% reduction in all-cause mortality (all statistically significant). There were very few adverse drug events and fewer adverse events overall in the treatment group.
Of note, exclusion criteria included a history of heart failure requiring anti-hypertensive medication, dementia, need for nursing care, an inability to stand or walk, and a creatinine more than 1.7 mg/dL. As well, the “target” SBP of 150 mmHg (which only half of the treatment group achieved) is still considered hypertensive according to the JNC 7 guidelines.
Bottom line: In some patients older than 80, treatment of hypertension may reduce the incidence of stroke, death from stroke, heart failure, and all-cause mortality.
Citation: Beckett N, Peters R, Fletcher A, et al. Treatment of hypertension in patients 80 years of age or older. N Engl J Med. 2008;358:1887-1898.
Background: Though there are clear trends toward shorter hospital stays after pulmonary embolism (PE), especially with the introduction of low molecular weight heparin, the optimal timing of discharge and the effect of decreased length of stay (LOS) on post-discharge mortality are unknown. Furthermore, there is no risk stratification strategy used to identify low-risk patients with PE who can safely be discharged early or treated in the outpatient setting.
Study Design: Retrospective cohort study.
Setting: 186 acute care hospitals in Pennsylvania from January 2000 to November 2002.
Synopsis: Using a statewide database of 15,531 patients discharged with pulmonary embolism (PE), the authors sought to identify patient and hospital factors associated with LOS and assess whether LOS was associated with post-discharge mortality.
Findings indicate there is considerable variation in LOS for PE between and within hospitals in Pennsylvania. The median LOS for patients with PE was six days; patients with a LOS of four or fewer days had significantly higher post-discharge mortality than patients hospitalized five to eight days. More than half the patients discharged at four or fewer days were classified as high-risk, with Pulmonary Embolism Severity Index (PESI) scores of III-V (3.1% to 24.5% risk of mortality at 30 days).
Although we cannot infer causation (i.e., early discharge=death), clinicians should be aware of the results and consider severity of illness (using PESI or other criteria) in the discharge decision in patients with PE. Future prognostic models and evidence-based criteria would be helpful to identify patients with PE who can be safely discharged early.
Bottom line: Physicians may inappropriately select patients with PE for early discharge who are at increased risk of complications.
Citation: Aujesky D, Stone RA, Kim S, et al. Length of hospital stay and post-discharge mortality in patients with pulmonary embolism. Arch Intern Med. 2008;168(7):706-712.
Background: Despite an increasing focus on providing appropriate end-of-life care, the majority of patients in developed countries die in the hospital. The circumstances and quality of care provided at the time of death are poorly described.
Study Design: Cross-sectional survey.
Setting: 613 departments in 200 French hospitals.
Synopsis: For 3,793 in-hospital deaths, the investigators surveyed the bedside nurses about the circumstances and details of the death. Twenty-three percent of the patients were admitted for end-of-life care, 29% had a malignancy, and 50% of patients were identified as terminally ill for three days prior to their death.
A family member or relative was present in only 25% of all deaths; 20% of patients were alone at the time of death. In the last few hours of life, up to 70% of patients had symptoms of respiratory distress, while only 44% received opiate analgesia. Only 35% of nurses were satisfied with the quality of death. Satisfaction increased with presence of family members and having written protocols for care at the end of life.
This large, multicenter study has limitations but provides a concerning snapshot of death in the hospital. Hospitalists should be aggressive about symptom control at the end of life as well as attempt to ensure patients are not alone at the time of death.
Bottom line: Many patients die in the hospital in some degree of respiratory distress and without family or friends at the bedside.
Citation: Ferrand E, Jabre P, Vincent-Genod C, et al. Circumstances of death in hospitalized patients and nurses’ perceptions. Arch Intern Med. 2008;168(8):867-875.
Background: Use of potentially inappropriate medications (PIM) in the elderly based on the Beers’ List is common in nursing homes, the emergency department (ED), and outpatient settings and is associated with adverse outcomes and hospitalization. Frequency of PIM use the inpatient setting has not been well studied.
Study Design: A retrospective cohort study.
Setting: 384 U.S. hospitals.
Synopsis: In this retrospective cohort study of 493,971 inpatients (older than 65) admitted with medical diagnoses to non-surgeons, PIM prescription was evaluated. Forty nine percent of all patients were prescribed at least one PIM, while 6% were prescribed three or more. In a multivariable model, physician specialty was associated with variation in high severity PIM (HSPIM) prescription. In comparison with internal medicine physicians, cardiologists (odds ratio [OR] 1.32) and pulmonologists (OR 1.10) were more likely to prescribe HSPIMs, while hospitalists (OR 0.90) and geriatricians (OR 0.60) were less likely. In addition, patient age older than 85 was associated with decreased HSPIM prescription (OR 0.59) compared with those younger than 85.
Compared with patients in the Midwest, patients in the South (OR 1.63) and West (OR 1.43) were more likely to prescribe HSPIMs, while those in the Northeast (OR 0.85) were less likely. Hospitals with geriatric services had less PIM use. The study couldn’t account for continuation of chronic medications and did not evaluate adverse outcomes from PIM prescribing.
Bottom line: PIM prescription to hospitalized geriatric patients is common and associated with provider and hospital characteristics.
Citation: Rothberg MB, Pekow PS, Liu F, et al. Potentially inappropriate medication use in hospitalized elders. J Hosp Med. 2008;3:91-102:91-102.
Background: The benefit of adjuvant corticosteroids in the treatment of bacterial meningitis in children in the developed world remains unclear; recent expert guidelines reflect this uncertainty.
Study Design: Retrospective cohort study.
Setting: Twenty-seven tertiary care hospitals in the United States.
Synopsis: Researchers examined 2,780 children with a primary diagnosis of bacterial meningitis discharged from 27 tertiary care centers in the U.S. from 2001-2006. Using a propensity analysis (to control for severity of illness), the study compared those who had received adjunctive corticosteroids with those who had not, with mortality and length of study (LOS) as primary outcomes.
The median age was nine months, 8.9% of children received corticosteroids, and the overall mortality rate was 4.2%. Adjuvent corticosteroids did not reduce mortality or LOS. The outcomes were unchanged in subgroup analyses.
Although limited by its retrospective design and lack of other outcome measures (e.g., hearing loss, neurological deficits), this study provides reasonable evidence that corticosteroid use in bacterial meningitis in children may not save lives or shorten LOS. Pediatric hospitalists may not want to routinely give steroids in this setting pending large randomized-controlled trials.
Bottom line: Adjunctive corticosteroids therapy in children with bacterial meningitis may not save lives or reduce LOS.
Citation: Mongelluzzo J, Mohamad Z, Ten Have TR, Shah SS. Corticosteroids and mortality in children with bacterial meningitis. JAMA. 2008;299(17):2048-2055.
Background: The current standard of care for the treatment of left main coronary artery disease is coronary-artery bypass grafting (CABG). With the advent of drug-eluting stents, there is growing interest in the use of percutaneous coronary intervention (PCI) to treat left main disease.
Study Design: Prospective observational study.
Setting: Twelve Korean cardiac centers.
Synopsis: From 2000 to 2006, patients with left main disease were treated with PCI or CABG at the discretion of the physician. Nearly 1,100 patients in each cohort were compared and evaluated for death and a composite outcome of death, myocardial infarction, or stroke. Propensity-matching was employed to control for confounders.
In the overall cohort matched by propensity score, there was no significant difference in death or the composite outcome between the PCI and CABG groups after three years. Type of stent (bare metal vs. drug-eluting) did not affect the outcome. Rates of target-vessel revascularization were significantly higher in the group that received stents.
The results are limited by the observational nature and the need for propensity analysis and yet provide an intriguing result. The standard of care for treatment of left main disease remains CABG, but clinicians may be more comfortable treating with stents while we await randomized-controlled trials.
Bottom line: In this observational study, PCI and CABG had similar outcomes in patients with left main disease.
Citation: Seung KB, Park D, Kim Y, Lee S. Stents versus coronary-artery bypass grafting for left main coronary artery disease. N Engl J Med. 2008;358:1781-1792.