MD Conference Express ATS 2013 - (Page 16)
CLINICAL TRIAL HIGHLIGHTS
16
July 2013
Figure 1. Change From Baseline in the 6-Minute
Walk Distance
Placebo (n=111)
Ambrisentan 10 mg/day (n=57)
Spironolactone (n=21)
Spironolactone+ambrisentan (n=10)
120
100
80
∆ 6MWD (m)
maintaining normal bioavailable levels of the vasodilator
and anti-remodeling molecule nitric oxide. Together,
these observations raised the possibility that coupling the
mineralocorticoid-receptor antagonist spironolactone with
therapies that inhibit the adverse effects of ETA-mediated
pulmonary vasoconstriction/remodeling may be a useful
therapeutic strategy for patients with PAH.
This study analyzed data from patients in the doubleblind, placebo-controlled Ambrisentan in Patients With
Moderate to Severe Pulmonary Arterial Hypertension
studies [ARIES-1 and -2; Galiè N et al. Circulation
2008] who were randomized to receive placebo or the
selective ETA antagonist ambrisentan (10 mg daily)
and in whom spironolactone use was reported. The
investigators elected to study patients randomized to
the maximum dose of ambrisentan because it was at
this dose that the greatest benefit on clinical outcome
was observed in the ARIES trial. Critiera for inclusion
in the spironolactone treatment group was as follows:
study drug use for ≥28 days, initiation of spironolactone
prior to enrollment or ≤28 days after first ARIES study
drug day, and discontinuation of spironolactone >28
days prior to the final ARIES study drug dose. Twentyone patients in the placebo group (21/132; 15.9%) and
10 patients in the ambrisentan group (10/67; 14.9%)
met the spironolactone criteria.
Patients treated with ambrisentan plus spironolactone
tended to have increased mean pulmonary vascular
resistance (14.5±6.0 vs 10.8±5.7 Wood units; p=0.07) and
plasma B-type natriuretic peptide (BNP) concentrations
(236.7 ng/L; 95% CI, 81.5 to 687.4 vs 131.7 ng/L; 95% CI,
88.0 to 197.2; p=0.24) compared with those treated with
ambrisentan alone.
On the primary endpoint of change from baseline in
6-minute walk distance at Week 12, patients treated with
ambrisentan plus spironolactone achieved a mean peak
mean change of +74.2 meters compared with +38.2 meters
for those treated with ambrisentan alone (p=0.11; Figure 1).
A similar trend was observed for the predetermined
secondary endpoints: ambrisentan plus spironolactone
was associated with a 1.7-fold improvement in BNP levels
(p=0.08) compared with ambrisentan alone at Week 12 and
a decrease in the geometric BNP mean of 66% compared
with 39% decrease for ambrisentan alone at Week 12.
World Health Organization functional status improved
by ≥1 class in 50.0% of patients treated with ambrisentan
plus spironolactone versus 21.6% of placebo-treated
patients (p=0.01). Additionally, none of the patients
treated with ambrisentan plus spironolactone reached the
clinical endpoints of progressive illness, PAH-associated
hospitalizations, and/or death versus 5.3% of patients
treated with ambrisentan only.
60
40
20
0
–20
0
4
Weeks
8
12
Reproduced with permission from B Maron, MD.
Limitations of the study include the retrospective design
and small sample size. In addition, aldosterone levels
were not measured in the ARIES trial nor were potential
mechanisms by which aldosterone influenced outcomes.
Additionally, the investigators recognized that use of
spironolactone may be a marker of more severe PAH and
that the clinical response observed in patients treated with
ambrisentan plus spironolactone reflects the enhanced
therapeutic efficacy of ambrisentan. Nevertheless, these
results support the hypothesis that spironolactone and ETA
antagonism may be beneficial in PAH, and, overall, results
from this study provide evidence to support future clinical
trials to characterize the efficacy of aldosterone inhibition
in the treatment of PAH.
Haloperidol Does Not Prevent
Delirium in Ventilated ICU Patients
Written by Emma Hitt, PhD
Treatment of ventilated patients in the intensive care unit
(ICU) with haloperidol or intravenous saline resulted
in similar rates of delirium- and coma-free days. Valerie
Page, MB, BCh, Wirral University Teaching Hospital NHS
Foundation Trust, Wirral, United Kingdom, presented
data from the Randomised, Double-Blind, PlaceboControlled Trial to Compare the Early Administration of
Intravenous Haloperidol Versus Placebo in the Prevention
and Treatment of Delirium in Critically Ill Ventilated
Patients [HOPE-ICU; ISRCTN83567338].
Between 55% and 80% of ventilated ICU patients have
delirium, with an estimated 65% unrecognized or untreated.
Although limited evidence supports the use of haloperidol
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Table of Contents for the Digital Edition of MD Conference Express ATS 2013
MD Conference Express ATS 2013
Contents
Prevention and Early Treatment of Acute Lung Injury
Nocturnal Noninvasive Ventilation Improves Outcomes in Multiple Disorders
Hospital Readmissions: Challenges and Opportunities
EBUS-TBNA: Accurate and Safe for Detecting Sarcoidosis
Data Link Obstructive Sleep Apnea and Type 2 Diabetes
Statin Use Improves Respiratory-Related Mortality in Patients With COPD
Addition of Spironolactone to Ambrisentan May Be a Novel Treatment Strategy to Improve Outcome in Patients With PAH
Haloperidol Does Not Prevent Delirium in Ventilated ICU Patients
Beraprost Plus Sildenafil Effective in Pulmonary Arterial Hypertension
Dupilumab Is Safe and Effective for Controlling Asthma Attacks
Once-Daily QVA149 Improves Breathlessness in COPD Patients
CPAP in CVD and OSA Does Not Significantly Improve Cardiovascular Biomarkers
CPAP Reduces BP in Patients With Resistant Hypertension and Obstructive Sleep Apnea
Effects of Obesity on COPD
Pulmonary Embolism
Ventilator-Associated Pneumonia
Lung Cancer Screening
Idiopathic Pulmonary Fibrosis
Non-Small-Cell Lung Cancer
MD Conference Express ATS 2013
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