Welcome to Scribd, the world's digital library. Read, publish, and share books and documents. See more
Download
Standard view
Full view
of .
Save to My Library
Look up keyword
Like this
2Activity
0 of .
Results for:
No results containing your search query
P. 1
Angiotensin-converting enzyme inhibitors and cardiovascular outcomes in patients on maintenance hemodialysis

Angiotensin-converting enzyme inhibitors and cardiovascular outcomes in patients on maintenance hemodialysis

Ratings: (0)|Views: 14 |Likes:
Published by Mahmoud Diaa

More info:

Published by: Mahmoud Diaa on Aug 16, 2011
Copyright:Attribution Non-commercial

Availability:

Read on Scribd mobile: iPhone, iPad and Android.
download as PDF, TXT or read online from Scribd
See more
See less

10/30/2012

pdf

text

original

 
 Angiotensin-converting enzyme inhibitors andcardiovascular outcomes in patients onmaintenance hemodialysis
Tara I. Chang, MD, MS,
a
David Shilane, PhD,
b
Steven M. Brunelli, MD, MSCE,
c
 Alfred K. Cheung, MD,
d,e
Glenn M. Chertow, MD, MPH,
a
and Wolfgang C. Winkelmayer, MD, MPH, ScD
a
 Palo Alto, CA; Boston, MA; and Salt Lake City, UT 
Background
Persons with end-stage renal disease (ESRD) on hemodialysis carry an exceptionally high burden of cardiovascular disease. Angiotensin-converting enzyme inhibitors (ACEIs) are recommended for patients on dialysis, but thereare few data regarding their effectiveness in ESRD.
Methods
We conducted a secondary analysis of results of the HEMO study, a randomized trial of dialysis dose andmembrane flux in patients on maintenance hemodialysis. We focused on the nonrandomized exposure of ACEI use, usingproportional hazards regression and a propensity score analysis. The primary outcome was all-cause mortality. Secondary outcomes examined in the present analysis were cardiovascular hospitalization, heart failure hospitalization, and thecomposite outcomes of death or cardiovascular hospitalization and death or heart failure hospitalization.
Results
In multivariable-adjusted analyses, there were no significant associations among ACEI use and mortality (hazardratio 0.97, 95% CI 0.82-1.14), cardiovascular hospitalization, and either composite outcome. Angiotensin-converting enzymeinhibitor use was associated with a higher risk of heart failure hospitalization (hazard ratio 1.41, 95% CI 1.11-1.80). In thepropensity score
matched cohort, ACEI use was not significantly associated with any outcomes, including heart failurehospitalization.
Conclusions
In a well-characterized cohort of patients on maintenance hemodialysis, ACEI use was not significantly associated with mortality or cardiovascular morbidity. The higher risk of heart failure hospitalization associated with ACEI usemay not only reflect residual confounding but also highlights gaps in evidence when applying treatments proven effective in thegeneral population to patients with ESRD. Our results underscore the need for definitive trials in ESRD to inform the treatment of cardiovascular disease. (Am Heart J 2011;162:324-30.)
 Angiotensin-converting enzyme inhibitors (ACEIs) havebeen shown to reduce mortality and cardiovasculamorbidity in a variety of clinical scenarios, such aspostacute myocardial infarction or in patients with heartfailure or left ventricular dysfunction.
Persons withend-stage renal disease (ESRD) on dialysis carry anexceptionally high burden of cardiovascular disease, with45% of all deaths attributed to cardiovascular causes.
4
 Although current national clinical practice guidelines
5
recommend the use of ACEIs in patients on maintenancedialysis, there are few data regarding their effectivenessfor cardiovascular disease prevention in this populationbecause randomized clinical trials of ACEIs systematically excluded patients with ESRD.Given the uncertainty surrounding the effectiveness of  ACEIs in patients on maintenance hemodialysis, weconducted a secondary analysis of data from the HEMOstudy.
6
The HEMO study data have several advantagesover previous observational studies, in that the datacontain exceptionally detailed clinical information, allow- ing for improved case-mix adjustment, and clinicaloutcomes were rigorously adjudicated using standardizedcriteria rather than determined by administrative codes. We hypothesized that subjects receiving ACEIs at study entry would have lower risks of mortality and
From the 
Division of Nephrology, Stanford University School of Medicine, Palo Alto, CA,
Department of Health Research and Policy, Stanford University School of Medicine, Palo Alto, CA,
Renal Division, Department of Medicine, Brigham and Women's Hospital,Harvard Medical School, Boston, MA,
Medical Service, Veterans Affairs Salt Lake City Healthcare System, Salt Lake City, UT, and 
Division of Nephrology & Hypertension,University of Utah, Salt Lake City, UT.Submitted March 9, 2011; accepted May 3, 2011.Reprint requests: Tara I. Chang, MD, MS, Stanford University School of Medicine Divisionof Nephrology, 780 Welch Road, Suite 106, Palo Alto, CA 94304.E-mail:tichang@stanford.edu 0002-8703/$ - see front matter © 2011, Mosby, Inc. All rights reserved.doi:10.1016/j.ahj.2011.05.004
 
cardiovascular morbidity compared with subjects whodid not receive this class of medication.
Methods
Study population
Details of the HEMO study protocol have been publishedpreviously.
Briefly, the HEMO study was a randomized clinicaltrial of 1,846 prevalent hemodialysis patients between 18 and 80 years old from 15 US clinical centers composed of 72 dialysisunits. Subjects were enrolled between March 1995 and October 2000 and randomly assigned in a 2 × 2 factorial design tostandard or high equilibrated Kt/V urea and low- or high-fluxdialyzers. Subjects were followed up until death or theadministrative end of study (December 2001). When studyingthe end point of death, we censored subjects at time of kidney transplant only because the HEMO study continued to collectsurvival information even after transfer to a nonparticipatingclinical center. However, when studying end points thatincluded hospitalization, we censored subjects at the time of kidney transplant and transfer to a nonparticipating clinicalcenter because information regarding hospitalization was notcollected after patient transfer to nonparticipating clinicalcenters in the HEMO study.
Medication use
In the HEMO study, use of the following classes of medications was ascertained from the hemodialysis chart or fromthe patient: ACEIs,angiotensin II receptor blockers (ARBs),
β
-blockers, calcium-channel blockers,
α
-1 antagonists (eg,terazosin), minoxidil, adrenergic stimulants (eg, clonidine),erythropoietin, aspirin, warfarin, nitrates, and vitamin Dreplacement (either oral or intravenous). Dose was notrecorded. Although both ARBs and ACEIs inhibit the renin- angiotensin-aldosterone system, these 2 classes of medicationsmay have different associations with outcomes. We were unableto analyze ARB users separately because very few subjects wereusing ARBs at the time of the HEMO study (n = 26). We,
Table I.
Baseline characteristics of the HEMO study cohort before and after propensity score matching
Baseline characteristicsBefore propensity score matching After propensity score matching ACEI nonusern = 1362 ACEI usern = 458
Std Diff (%) ACEI nonusern = 408 ACEI usern = 408
Std Diff (%)
 Age, y 58.2 (13.8) 56.0 (14.8) .004 15.4 57.1 (14.4) 56.6 (14.6) .6 3.4Female sex 56.2 55.5 .8 1.0 55.4 55.2 .9 0.3Black race 63.4 60.7 .3 3.9 61.8 60.1 .6 2.5Duration of dialysis, y 3.9 (4.4) 3.5 (4.2) .1 9.3 3.7 (4.5) 3.6 (4.3) .9 2.3Married/partnered 37.7 42.6 .06 7.1 43.4 41.7 .6 2.4Body mass index, kg/m
2
25.6 (5.3) 24.8 (5.2) .003 15.2 25.1 (4.9) 25.1 (5.2) .9 0.3History of Ischemic heart disease 39.0 38.9 .96 0.1 41.9 40.9 .8 1.4 Arrhythmias 30.6 31.2 .8 0.9 31.9 32.4 .9 0.8Heart failure 35.8 50.0
b
.0001 20.5 47.6 45.8 .6 2.6Other heart conditions 61.8 65.9 .1 6.0 69.1 65.4 .3 5.6Cerebrovascular disease 18.7 22.3 .1 6.3 21.3 21.8 .9 0.9Peripheral vascular disease 24.7 27.5 .2 4.5 26.2 27.5 .7 2.1Diabetes mellitus 42.7 49.3 .01 9.4 47.3 49.3 .6 2.8Musculoskeletal disease 45.3 39.1 .02 8.9 42.7 40.7 .6 2.9Nonvascular nervous system disease 37.0 37.6 .8 0.9 38.7 37.8 .8 1.3Gastrointestinal disease 36.6 37.6 .7 1.5 36.3 38.7 .5 3.5Hepatic disease 17.6 16.8 .7 1.5 18.4 17.7 .8 1.3Malignancy 9.2 8.1 .5 2.8 9.8 8.6 .5 2.9Ophthalmologic disease 27.5 32.1 .06 7.1 31.6 31.9 .9 0.5Sick in past 7 d 22.2 28.6 .005 10.4 24.5 28.2 .2 5.9Predialysis systolic blood pressure, mm Hg 150 (22) 158 (22)
b
.0001 36.3 156 (22) 156 (22) .9 0.9Serum potassium, mEq/L 4.8 (0.8) 5.0 (0.8) .0003 25.0 4.9 (0.8) 4.9 (0.7) .9 1.0Serum albumin, g/dL 3.6 (0.36) 3.6 (0.37) .0003 2.8 3.6 (0.35) 3.6 (0.37)
N
.99 0.0Residual urea clearance adjusted to Watson's V, mL/min per 35 L 0.2 (0.4) 0.3 (0.6) .005 19.9 0.2 (0.4) 0.3 (0.4) .7 2.Other baseline medication use
β
-Blockers 27.9 35.2 .003 11.9 34.8 34.1 .8 1.0Calcium-channel blockers 46.8 55.5 .001 13.4 56.4 53.7 .4 3.8Minoxidil 1.1 3.1 .004 11.4 2.5 2.9 .7 1. Adrenergic agonists 2.4 5.0 .005 12.7 4.7 3.9 .6 2.8Nitrates 16.1 20.3 .04 7.7 19.6 21.3 .5 3.0 Aspirin 25.9 33.4 .002 12.1 31.9 33.3 .7 2.1Coumadin 8.7 10.5 .3 4.8 11.8 10.5 .6 2.9
 Values are percentages or mean (SD).
value was calculated using
χ
2
test or 
tests as appropriate.
Std Diff 
, Standardized difference.
Chang et al
325
American Heart JournalVolume 162, Number 2
 
Figure 1326
Chang et al
American Heart JournalAugust 2011

You're Reading a Free Preview

Download
/*********** DO NOT ALTER ANYTHING BELOW THIS LINE ! ************/ var s_code=s.t();if(s_code)document.write(s_code)//-->