 |
|
Toleration of High Doses of Angiotensin-Converting Enzyme Inhibitors in Patients With Chronic Heart Failure
Results From the ATLAS Trial
Barry M. Massie, MD;
Paul W. Armstrong, MD;
John G. F. Cleland, MD;
John D. Horowitz, MD;
Milton Packer, MD;
Philip A. Poole-Wilson, MD;
Lars Rydén, MD
Arch Intern Med. 2001;161:165-171.
Background Treatment with angiotensin-converting enzyme (ACE) inhibitors reduces
mortality and morbidity in patients with chronic heart failure (CHF), but
most affected patients are not receiving these agents or are being treated
with doses lower than those found to be efficacious in trials, primarily because
of concerns about the safety and tolerability of these agents, especially
at the recommended doses. The present study examines the safety and tolerability
of high- compared with low-dose lisinopril in CHF.
Methods The Assessment of Lisinopril and Survival study was a multicenter, randomized,
double-blind trial in which patients with or without previous ACE inhibitor
treatment were stabilized receiving medium-dose lisinopril (12.5 or 15.0 mg
once daily [OD]) for 2 to 4 weeks and then randomized to high- (35.0 or 32.5
mg OD) or low-dose (5.0 or 2.5 mg OD) groups. Patients with New York Heart
Association classes II to IV CHF and left ventricular ejection fractions of
no greater than 0.30 (n = 3164) were randomized and followed up for a median
of 46 months. We examined the occurrence of adverse events and the need for
discontinuation and dose reduction during treatment, with a focus on hypotension
and renal dysfunction.
Results Of 405 patients not previously receiving an ACE inhibitor, doses in
only 4.2% could not be titrated to the medium doses required for randomization
because of symptoms possibly related to hypotension (2.0%) or because of renal
dysfunction or hyperkalemia (2.3%). Doses in more than 90% of randomized patients
in the high- and low-dose groups were titrated to their assigned target, and
the mean doses of blinded medication in both groups remained similar throughout
the study. Withdrawals occurred in 27.1% of the high- and 30.7% of the low-dose
groups. Subgroups presumed to be at higher risk for ACE inhibitor intolerance
(blood pressure, <120 mm Hg; creatinine,  132.6 µmol/L [1.5
mg/dL]; age, 70 years; and patients with diabetes) generally tolerated
the high-dose strategy.
Conclusions These findings demonstrate that ACE inhibitor therapy in most patients
with CHF can be successfully titrated to and maintained at high doses, and
that more aggressive use of these agents is warranted.
From the Departments of Medicine, University of California–San
Francisco and the Department of Veterans Affairs Medical Center, San Francisco
(Dr Massie), University of Alberta, Edmonton (Dr Armstrong), and University
of Hull, Kingston upon Hull, England (Dr Cleland); Cardiac Unit, University
of Adelaide, Adelaide, South Australia (Dr Horowitz); Department of Circulatory
Physiology, College of Physicians and Surgeons, Columbia University, New York,
NY (Dr Packer); Department of Cardiology, Imperial College School of Medicine,
University of London, London, England (Dr Poole-Wilson); and Department of
Medicine, the Karolinska Institutet, Stockholm, Sweden (Dr Rydén).
A complete listing of the participants in the Assessment of Lisinopril and
Survival (ATLAS) trial was published previously (Circulation.
1999;100:2317).
Corresponding author: Barry M. Massie, MD, Cardiology Division (111C),
Veterans Affairs Hospital, 4150 Clement St, San Francisco, CA 94121 (e-mail: Barry.Massie{at}med.va.gov). Reprints are not available from the authors.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati  Twitter
What's this?
THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES
|
2009 Focused Update Incorporated Into the ACC/AHA 2005 Guidelines for the Diagnosis and Management of Heart Failure in Adults: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines Developed in Collaboration With the International Society for Heart and Lung Transplantation
Hunt et al.
J Am Coll Cardiol 2009;53:e1-e90.
FULL TEXT
2009 Focused Update Incorporated Into the ACC/AHA 2005 Guidelines for the Diagnosis and Management of Heart Failure in Adults: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines: Developed in Collaboration With the International Society for Heart and Lung Transplantation
2005 WRITING COMMITTEE MEMBERS et al.
Circulation 2009;119:e391-e479.
FULL TEXT
Limited long term effects of a management programme for heart failure
Mejhert et al.
Heart 2004;90:1010-1015.
ABSTRACT
| FULL TEXT
Long-term retention of cardiac resynchronization therapy
Knight et al.
J Am Coll Cardiol 2004;44:72-77.
ABSTRACT
| FULL TEXT
Determinants of failure to prescribe target doses of angiotensin-converting enzyme inhibitors for heart failure
Manyemba et al.
Eur J Heart Fail 2003;5:693-696.
FULL TEXT
Aspirin-Angiotensin-Converting Enzyme Inhibitor Coadministration and Mortality in Patients With Heart Failure: A Dose-Related Adverse Effect of Aspirin
Guazzi et al.
Arch Intern Med 2003;163:1574-1579.
ABSTRACT
| FULL TEXT
Pharmacotherapy for Heart Failure in Patients with Renal Insufficiency
Shlipak
ANN INTERN MED 2003;138:917-924.
ABSTRACT
| FULL TEXT
Differences between general practitioners and cardiologists in diagnosis and management of heart failure: a survey in every-day practice
Rutten et al.
Eur J Heart Fail 2003;5:337-344.
ABSTRACT
| FULL TEXT
Mode of death in heart failure: findings from the ATLAS trial
Poole-Wilson et al.
Heart 2003;89:42-48.
ABSTRACT
| FULL TEXT
Review: The pharmacokinetics and pharmacodynamics of angiotensin-receptor blockers in end-stage renal disease
Sica and Gehr
Journal of Renin-Angiotensin-Aldosterone System 2002;3:247-254.
ABSTRACT
Neurohormonal and clinical responses to high- versus low-dose enalapril therapy in chronic heart failure
Wilson Tang et al.
J Am Coll Cardiol 2002;39:70-78.
ABSTRACT
| FULL TEXT
Failing ageing hearts
Petrie et al.
Eur Heart J 2001;22:1978-1990.
Management of congestive heart failure: How well are we doing?
Giannetti
CMAJ 2001;165:305-306.
FULL TEXT
|
