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qwest.net

An explanation for the higher incidence of cardiovascular disease and heart failure in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) with doxazosin and the Vasodilator Heart Failure Trial (V-HeFT) with prazosin might be decreased expression of heat shock proteins. Heat shock proteins help to protect cells from ischemic injury by decreasing oxidation, suppressing cytokine action, refolding damaged proteins, and decreasing apoptosis. I hypothesize that alpha-adrenergic blockade decreases heat shock protein levels, thus making the heart and vascular system vulnerable to injury from pathologic processes such as ischemia, hypertension, oxidation or inflammation. Similarly, poor cardiovascular outcomes with calcium-channel blockers might be due to decreased expression of heat shock proteins.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11806806&dopt=Abstract [PubMed - as supplied by publisher]

ehmc.com

This commentary has two purposes: to summarize the rationale, design and initial results of the Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) trial; and to provide a history of the response to ALLHAT that led to a civil action and a Citizens Petition that was the basis for a public hearing by the US Food and Drug Administration, in May 2001. The author concludes that the results of ALLHAT should be widely disseminated. All clinicians must be warned that initial therapy with doxazosin (and possibly other alpha1 blockers) is definitely inferior to low dose diuretic treatment for patients at high risk for cardiovascular disease, such as those enrolled in ALLHAT.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11806807&dopt=Abstract [PubMed - as supplied by publisher]

bu.edu

The lowering of high blood pressure is supposed to protect target organs from hypertensive damage. The Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial was designed to compare the cardioprotective properties of three antihypertensives from different classes (lisinopril, amlodipine and doxazosin) with chlorthalidone. Despite effective blood pressure lowering and a favorable metabolic profile, the doxazosin arm of the trial had a significantly higher relative risk of cardiovascular disease and heart failure compared with the chlorthalidone arm. This article speculates on possible causes for this unexpected result and suggests that the culprit may be accentuation of the vascular effects of vasopressin, which are maximized under alpha-adrenergic blockade. These findings may have implications for the large number of older men who receive monotherapy with alpha-blockers for treatment of prostatic symptoms.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11806808&dopt=Abstract [PubMed - as supplied by publisher]





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