Document View - ProQuest

http://proquest.umi.com/pqdweb?index=20&sid=2&srchmode=1&vins...

Databases selected: Multiple databases...

Do diuretics do more harm than good?

Jillene Magill-Lewis. Drug Topics. Oradell: Oct 23, 2006. Vol. 150, Iss. 20; pg. 14, 1 pgs
Abstract (Summary)

New evidence indicates that traditional diuretics may be more harmful than beneficial for heart failure patients, while some drugs currently contraindicated could be beneficial. These suggets and more were presented at the Heart Failure Society of America's 10th annual meeting in Seattle last month. Two classes of drugs, biguanides and thiazolinediones (TZDs), increase sensitivity to insulin and could potentially reduce morbidity in diabetic heart failure patients. TZDs are approved for use only in early heart failure. Current diuretics do not always reduce edema, and some may cause more harm than good. So far, the vasopressin antagonists have produced diuresis and reduced the need for other diuretics, such as furosemide. They may also reduce mortality rates.

Full Text (648 words)

Copyright Advanstar Communications, Inc. Oct 23, 2006 New evidence indicates that traditional diuretics may be more harmful than beneficial for heart failure patients, while some drugs currently contraindicated could be beneficial. These nuggets and more were presented at the Heart Failure Society of America's 10th annual meeting in Seattle last month. Metformin and TZDs Diabetes and heart failure are not a healthy combination. "Patients with diabetes do have worsening long-term outcomes," said W. H. Wilson Tang, M.D., assistant professor of medicine at Cleveland Clinic Lerner College of Medicine. Two classes of drugs, biguanides and thiazolinediones (TZDs), increase sensitivity to insulin and could potentially reduce morbidity in diabetic heart failure patients, Tang said. Metformin, the only biguanide available in the United States, is contraindicated in heart failure. Phenformin, an early biguanide, caused lactic acidosis, and metformin has been "guilty by association" ever since, said Tang. Three cases of lactic acidosis have been reported with metformin in 100,000 patient years of treatment-about equal to the risk of lactic acidosis in patients not on metformin. TZDs are approved for use only in early heart failure. Increased risk of edema has been the main concern, said Tang. In clinical studies, despite edema and weight gain, heart failure mortality did not differ. Both TZDs now on the marketpioglitazone (Actos, Takeda), and rosiglitazone (Avandia, GlaxoSmithKline)-have shown a wide range of heart benefits, Tang said. Whether biguanides and TZDs are safe and effective in heart failure patients remains to be seen, but "risk concerns for metf ormin and the TZDs have not translated into increased mortality risks," Tang said. Targeting insulin resistance Insulin resistance plays a key role in heart failure. "In the absence of other risk factors, heart failure itself is associated with whole body and heart insulin resistance," said Richard P. Shannon, M.D., chairman, department of medicine, Allegheny General Hospital, Pittsburgh. He has been researching the mechanism of insulin resistance in cardiac muscle. He believes cardiac insulin resistance may be due to decreased mitochondrial function and decreased oxidation. There is glucose present for cardiac muscle to consume, but it is unable to do so; the heart is starving in the presence of plenty. A series of peptides called glucagon-like peptides (GLPs) may offer a remedy. He has studied one-GLP-I-to see if it would reverse cardiac insulin resistance. In the clinical study, a subcutaneous infusion of GLP-I for 10 weeks yielded a clinical benefit. The drug was insulinomimetic and was associated with minimal risk of hypoglycemia. GLP-I suppressed glucagons, increased contractility, and increased glucose uptake without changing plasma insulin. Preserving renal function "Renal dysfunction is common in patients with acute decompensated heart failure," said Michael M. Givertz, M.D., codirector of the cardiomyopathy and heart failure program at Brigham & Women's Hospital, Boston. "And the problem is worse than we thought."

1 of 3

11/04/2011 17:16

Document View - ProQuest

http://proquest.umi.com/pqdweb?index=20&sid=2&srchmode=1&vins...

Enlarge 200% Enlarge 400%

2 of 3

11/04/2011 17:16

Document View - ProQuest

http://proquest.umi.com/pqdweb?index=20&sid=2&srchmode=1&vins...

Current diuretics do not always reduce edema, and some may cause more harm than good. "Loop diuretics appear safe in the short term but activate RAAS in the longer term," said Mark C. P. Haigney, M.D., an electrophysiologist in the division of cardiology at Uniformed Services University of the Health Sciences in Bethesda, Md. The renin-angiotensinaldosterone system (RAAS) regulates blood volume and pressure. Haigney's animal study found that furosemide decreased survival by 40% when used during heart failure. Adenosine antagonists may be a novel approach to diuresis and can improve renal function and blood flow, Givertz said. Ongoing studies are evaluating safety and efficacy in this new class of drugs. Another new alternative to diuretics is the class of vasopressin antagonists. This group of drugs induces electrolytesparing diuresis and can correct hyponatremia, if present. Three vasopressin antagonists are currently under study, tolvaptan (V2 selective); lixivaptan (V2 selective); and conivaptan (Via and V2 balanced). So far, the vasopressin antagonists have produced diuresis and reduced the need for other diuretics, such as furosemide. They may also reduce mortality rates.
[Author Affiliation] Jillene Magill-Lewis, R.Ph. [Author Affiliation] THE AUTHOR is a medical writer based in the Seattle area. Indexing (document details) Subjects: Classification Codes Locations: Companies: Author(s): Author Affiliation: Diuretics, Mortality, Heart failure, Annual meetings, Antagonist drugs, Associations 9190, 8641, 9540 United States--US Heart Failure Society of America (NAICS: 813212 ) Jillene Magill-Lewis Jillene Magill-Lewis, R.Ph. THE AUTHOR is a medical writer based in the Seattle area. Document types: Document features: Section: Publication title: Source type: ISSN: News Illustrations RX CARE Drug Topics. Oradell: Oct 23, 2006. Vol. 150, Iss. 20; pg. 14, 1 pgs Periodical 00126616

ProQuest document ID: 1164264411 Text Word Count Document URL: 648 http://proquest.umi.com/pqdweb?did=1164264411&sid=2&Fmt=4&cl ientId=64099&RQT=309& VName=PQD

Copyright 2011 ProQuest LLC. All rights reserved.

3 of 3

11/04/2011 17:16