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| ID | Type | Description | Link |
|---|---|---|---|
| IRB# 00011909 |
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There is now strong evidence from clinical trials that carvedilol therapy in heart failure is superior to therapy with metoprolol. Not only does carvedilol have superior effects on lipid profiles, insulin sensitivity, renal blood flow, and reversal of pathologic remodeling but also its use is associated with fewer deaths compared to metoprolol. These facts make it important to carefully define how metoprolol and carvedilol are pharmacologically different. One potential difference is α1-AR antagonism. If we demonstrate that these α1-AR effects are preserved with chronic therapy, then α1-AR blockade may have an important role in carvedilol favorably altering the natural history of heart failure. On the other hand, if we demonstrate that tolerance to the α1-AR blockade effect of carvedilol decreases with time, then it would be unlikely that this pharmacologic property contributes to the efficacy of carvedilol. In such a case other pharmacologic properties, such as antioxidant activity, would appear to be important. These results will help guide future studies into CHF and AR blockade.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| A | Other | All patients undergo repeated phenylephrine infusions during standard up-titration and maintenance of carvedilol treatment. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| phenylephrine | Drug | All patients undergo repeated phenylephrine infusions during standard up-titration and maintenance of carvedilol treatment. |
|
| Measure | Description | Time Frame |
|---|---|---|
| The primary objective of this study is to determine if tolerance to α1-AR blockade develops with the chronic administration of carvedilol in heart failure patients. | Oct 2003-Aug 2008 |
| Measure | Description | Time Frame |
|---|---|---|
| All patients undergo repeated phenylephrine infusions during standard up-titration and maintenance of carvedilol treatment. | Oct 2003-Aug 2008 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Mark Munger, PharmD | Professor, Pharmacotherapy | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Utah | Salt Lake City | Utah | 84112 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 18657662 | Result | Van Tassell BW, Rondina MT, Huggins F, Gilbert EM, Munger MA. Carvedilol increases blood pressure response to phenylephrine infusion in heart failure subjects with systolic dysfunction: evidence of improved vascular alpha1-adrenoreceptor signal transduction. Am Heart J. 2008 Aug;156(2):315-21. doi: 10.1016/j.ahj.2008.04.004. Epub 2008 Jun 20. |
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| ID | Term |
|---|---|
| D006333 | Heart Failure |
| ID | Term |
|---|---|
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
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| ID | Term |
|---|---|
| D010656 | Phenylephrine |
| ID | Term |
|---|---|
| D004983 | Ethanolamines |
| D000605 | Amino Alcohols |
| D000438 | Alcohols |
| D009930 | Organic Chemicals |
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| D000588 |
| Amines |