The management of acute hypertension in patients with renal dysfunction: labetalol or nicardipine?

STUDY OBJECTIVES: To compare the safety and efficacy of U.S. Food and Drug Administration (FDA)-recommended doses of labetalol and nicardipine for hypertension (HTN) management in a subset of patients with renal dysfunction (RD). DESIGN: Randomized, open label, multicenter prospective clinical trial. SETTING: Thirteen United States tertiary care emergency departments. PATIENTS OR PARTICIPANTS: Subgroup analysis of the Evaluation of IV Cardene (Nicardipine) and Labetalol Use in the Emergency Department (CLUE) clinical trial. The subjects were 104 patients with RD (i.e., creatinine clearance < 75 mL/min) who presented to the emergency department with a systolic blood pressure (SBP) ≥ 180 mmHg on 2 consecutive readings and for whom the emergency physician felt intravenous antihypertensive therapy was desirable. INTERVENTIONS: The FDA recommended doses of either labetalol or nicardipine for HTN management. MEASUREMENTS: The number of patients achieving the physician's predefined target SBP range within 30 minutes of treatment. RESULTS: Patients treated with nicardipine were within target range more often than those receiving labetalol (92% vs. 78%, P = 0.046). On 6 SBP measures, patients treated with nicardipine were more likely to achieve the target range on either 5 or all 6 readings than were patients treated with labetalol (46% vs. 25%, P = 0.024). Labetalol patients were more likely to require rescue medication (27% vs. 17%, P = 0.020). Adverse events thought to be related to either treatment group were not reported in the 30-minute active study period, and patients had slower heart rates at all time points after 5 minutes (P < 0.01). CONCLUSIONS: In severe HTN with RD, nicardipine-treated patients are more likely to reach a target blood pressure range within 30 minutes than are patients receiving labetalol. CLINICAL IMPLICATIONS: Within 30 minutes of administration, nicardipine is more efficacious than labetalol for acute blood pressure control in patients with RD.

CLUE: a randomized comparative effectiveness trial of IV nicardipine versus labetalol use in the emergency department.

INTRODUCTION: Our purpose was to compare the safety and efficacy of food and drug administration (FDA) recommended dosing of IV nicardipine versus IV labetalol for the management of acute hypertension. METHODS: Multicenter randomized clinical trial. Eligible patients had 2 systolic blood pressure (SBP) measures ≥180 mmHg and no contraindications to nicardipine or labetalol. Before randomization, the physician specified a target SBP ± 20 mmHg (the target range: TR). The primary endpoint was the percent of subjects meeting TR during the initial 30 minutes of treatment. RESULTS: Of 226 randomized patients, 110 received nicardipine and 116 labetalol. End organ damage preceded treatment in 143 (63.3%); 71 nicardipine and 72 labetalol patients. Median initial SBP was 212.5 (IQR 197, 230) and 212 mmHg (IQR 200,225) for nicardipine and labetalol patients (P = 0.68), respectively. Within 30 minutes, nicardipine patients more often reached TR than labetalol (91.7 vs. 82.5%, P = 0.039). Of 6 BP measures (taken every 5 minutes) during the study period, nicardipine patients had higher rates of five and six instances within TR than labetalol (47.3% vs. 32.8%, P = 0.026). Rescue medication need did not differ between nicardipine and labetalol (15.5 vs. 22.4%, P = 0.183). Labetalol patients had slower heart rates at all time points (P < 0.01). Multivariable modeling showed nicardipine patients were more likely in TR than labetalol patients at 30 minutes (OR 2.73, P = 0.028; C stat for model = 0.72) CONCLUSIONS: Patients treated with nicardipine are more likely to reach the physician-specified SBP target range within 30 minutes than those treated with labetalol.

Outcomes associated with small changes in normal-range cardiac markers.

INTRODUCTION: Troponin concentrations rising above an institutional cutpoint are used to define acute myocardial necrosis, yet it is uncertain what outcomes are associated with fluctuations in troponin that do not exceed this level. We evaluate the association between troponin fluctuations below an institutional upper limit of normal and acute coronary syndrome (ACS). MATERIALS AND METHODS: This was a post hoc analysis of the Internet tracking registry of ACS (i*trACS), which describes patients presenting to emergency departments (EDs) with suspected ACS across the spectrum of risk. Patients were included in this registry if they were at least 18 years old and had suspected ACS at the time of their ED visit. Inclusions in this analysis required that patients had at least 1 cardiac marker (creatine kinase-MB [CK-MB], troponin T, or troponin I) drawn twice within 6 hours of presentation, with both measures being below the institution's upper limit of normal. A marker change was defined as either an increase or decrease that exceeded 15% of the institutional upper limit of normal. Acute coronary syndrome was defined as a positive stress test, documented myocardial infarction, coronary revascularization, or death within 30 days of their ED admission. RESULTS: Of 17,713 patient visits, 2162 met inclusion and exclusion criteria. There were 1872 patient visits with 2 troponin results and 1312 with 2 CK-MB results. Patient visits with increasing troponin had increased odds of ACS compared with those with stable troponin levels (odds ratio, 3.6; 95% confidence interval, 1.4-9.2). Changing CK-MB and decreasing troponin were not associated with increased odds of ACS. CONCLUSIONS: Small increases in troponin concentration below the upper limit of normal are associated with increased odds of ACS.

Outcomes associated with nesiritide administration for acute decompensated heart failure in the emergency department observation unit: a single center experience.

The authors' purpose was to determine 30- and 180-day readmission and mortality rates for acutely decompensated heart failure patients receiving nesiritide in the emergency department observation unit. The authors conducted a retrospective evaluation of all patients admitted to the emergency department observation unit, stratified by nesiritide administration, from January 2002 to January 2004. Eligible patients had a primary diagnosis of acutely decompensated heart failure. Observation unit treatment was by previously published protocols, except for nesiritide administration, which was per attending physician choice. Of 595 patients, 196 (33%) received nesiritide. The crude and adjusted odds ratios comparing readmission rates and mortality rates of the nesiritide group with the control group failed to demonstrate significant differences at either the 30- or the 180-day endpoints. The use of nesiritide for acute decompensated heart failure in the emergency department observation unit is not associated with mortality or readmission differences compared with standard therapy alone.

Initial emergency department systolic blood pressure predicts left ventricular systolic function in acute decompensated heart failure.

Ejection fraction (EF) is often unknown in patients who present with acute decompensated heart failure (ADHF). The objective of this study was to determine whether a patient's systolic blood pressure is associated with their left ventricular EF. This study was a retrospective chart review of all patients admitted to an emergency department (ED) observation unit from January 2002 to December 2004. A low EF was defined as <40%. Among 475 patients, the median age was 72 years, 53% were men, 40% were white, 59% were black, and 59% had a low EF. Patients with low EFs were more likely male ( P<.0001), with prior congestive heart disease ( P<.0001), longer QRS duration ( P<.0001), left bundle branch block ( P<.0001), and higher B-type natriuretic peptide ( P<.0001). The low EF group was less likely to have diabetes ( P<.0001). Adjusted odds ratios for an EF >or=40% were significant at all systolic blood pressure readings >120 mm Hg. Having an ED systolic BP >120 mm Hg is associated with significantly higher rates of preserved left ventricular systolic function in patients with ADHF.

Emergency department stabilization of heart failure.

Optimizing heart failure management begins in the emergency department. Prompt recognition and treatment of underlying pathophysiology can improve patient outcomes. A review of therapeutic options is provided, with the goal of providing best practices in patient care.

Illicit stimulant use in a United States heart failure population presenting to the emergency department (from the Acute Decompensated Heart Failure National Registry Emergency Module).

Illicit stimulant drug use may have a profound clinical impact in acute decompensated heart failure (ADHF). The chronic use of cocaine and methamphetamine may lead to overt cardiomyopathy and ADHF. The Acute Decompensated Heart Failure National Registry Emergency Module (ADHERE-EM) collected data on patients presenting to emergency departments with ADHF at 83 geographically dispersed hospitals in the United States. This registry was queried to determine the rate of self-reported illicit drug use in emergency department patients presenting with ADHF and compare these patients with those without illicit drug use. The registry enrolled 11,258 patients with ADHF with drug use data from January 2004 to March 2006. Of these patients, 594 (5.3%) self-reported current or past stimulant drug use. Compared with nonusers, these patients were more likely to be younger (median age 49.7 vs 76.1 years), to be African American (odds ratio 11.9, 95% confidence interval 9.8 to 14.4), and to have left ventricular ejection fractions <40% (odds ratio 3.4, 95% confidence interval 2.8 to 4.2). Admitted users had no difference in mortality (adjusted odds ratio 0.83, 95% confidence interval 0.25 to 2.72) compared with nonusers. In conclusion, data from ADHERE-EM suggest that a clinically important percentage of patients with ADHF report the use of illicit stimulant drugs. Although these patients are younger with a greater degree of LV dysfunction, they did not have greater risk-adjusted mortality.

Venous thromboembolism prophylaxis in hospitalized heart failure patients.

BACKGROUND: Venous thromboembolism (VTE) is a concerning problem for hospitalized heart failure (HF) patients. Current recommendations are that all hospitalized New York Heart Association Class III or IV HF patients should receive VTE prophylaxis. Our purpose was to describe the rate of use and the characteristics of patients receiving VTE prophylaxis in the Acute Decompensated Heart Failure National Registry (ADHERE). METHODS AND RESULTS: HF hospitalization episodes in ADHERE were analyzed. Patients were excluded from analysis if they were receiving Coumadin or intravenous heparin, had elevated troponin levels, underwent cardiac catheterization or dialysis before or during hospitalization, or were initially admitted to the intensive care unit. VTE prophylaxis was defined as low-molecular-weight or subcutaneous unfractionated heparin administered at any time during hospitalization and intravenous vasoactive therapy was defined as any inotrope, inodilator, or vasodilator. Chi-square, analysis of variance, and Wilcoxon tests were used for univariate and multivariate analyses. Logistic regression was used to evaluate outcomes. A total of 155,073 entries were evaluated, with 71,376 eligible for VTE prophylaxis; 21,847 (31%) received VTE prophylaxis. VTE prophylaxis patients were more often African American (28% versus 21%) or admitted from the emergency department (84% versus 79%), compared with those who did not receive VTE prophylaxis (both P < .0001). Medical history and initial presentation characteristics were similar, except edema, which was more likely in VTE prophylaxis patients (71% versus 66%, P < .0001). Patients receiving VTE prophylaxis more often received an intravenous vasoactive agent (23% versus 18%), angiotensin-converting enzyme inhibitor (61% versus 54%), or beta-blocker (63% versus 58%) during their hospitalization and were more likely discharged on an angiotensin-converting enzyme inhibitor (53% versus 49%) or beta-blocker (57% versus 54%) than non-VTE prophylaxis patients, all P < .0001. VTE prophylaxis patients were more often admitted to the intensive care unit (4.8% versus 2.5%, P < .0001) and had longer median hospital stays (4.2 versus 3.8 days, P < .0001). Mortality was similar between cohorts (3.0% versus 2.9%, P = .69). CONCLUSIONS: Despite recommendations that all hospitalized New York Heart Association III and IV CHF patients receive venous thromboembolic disease prophylaxis, less than one third of eligible patients receive this guideline recommended therapy.