Was the ALLHAT (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial) study with doxazosin stopped due to increased cardiovascular events?

From the Guidelines

Yes, the ALLHAT study's doxazosin arm was stopped early due to increased cardiovascular events, specifically a 2.04-fold increase in relative risk of developing heart failure compared with chlorthalidone treatment. The ALLHAT trial, a landmark hypertension study, found that participants taking doxazosin (an alpha-blocker) had a higher risk of combined cardiovascular disease outcomes and nearly twice the risk of heart failure compared to those taking chlorthalidone (a thiazide-type diuretic) 1. The doxazosin arm was terminated early after the Data Safety Monitoring Board observed these concerning trends. This finding significantly impacted clinical practice, as it demonstrated that alpha-blockers like doxazosin were less effective than diuretics in preventing cardiovascular complications of hypertension.

The results suggested that doxazosin's mechanism of action, which involves blocking alpha-1 adrenergic receptors to reduce peripheral vascular resistance, may not provide the same cardiovascular protection as diuretics despite similar blood pressure lowering effects. This outcome from ALLHAT contributed to the recommendation that alpha-blockers should not be first-line agents for uncomplicated hypertension treatment. The study's findings were further supported by subsequent guidelines and reviews, including the 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults 1.

Key points to consider include:

• The ALLHAT study's doxazosin arm was stopped early due to increased cardiovascular events
• Doxazosin was associated with a higher risk of heart failure compared to chlorthalidone
• Alpha-blockers like doxazosin are not recommended as first-line agents for uncomplicated hypertension treatment
• The mechanism of action of doxazosin may not provide the same cardiovascular protection as diuretics despite similar blood pressure lowering effects.

From the Research

Study Overview

• The ALLHAT (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial) study is not directly mentioned in the provided evidence.
• However, the studies provided do discuss the use of doxazosin in the treatment of hypertension.

Doxazosin Studies

• A study published in 2009 2 found that doxazosin was a well-tolerated and effective drug for patients with resistant arterial hypertension.
• Another study published in 2008 3 reviewed the role of doxazosin in the current treatment of hypertension and found that it was a valuable add-on antihypertensive treatment option.
• A study published in 1995 4 found that doxazosin had a beneficial effect on some of the risk factors associated with coronary heart disease.
• A study published in 1988 5 found that doxazosin was a suitable drug for consideration as first-line therapy in mild to moderate essential hypertension.
• A study published in 2007 6 found that the addition of a low dose of doxazosin effectively reduced blood pressure in patients taking calcium channel blockers and angiotensin II receptor blockers or angiotensin-converting enzyme inhibitors.

ALLHAT Study

• Although the provided evidence does not directly mention the ALLHAT study, it is known that the doxazosin arm of the ALLHAT study was stopped early due to an increased risk of cardiovascular events, particularly heart failure, compared to the chlorthalidone arm 2, 3 is not relevant to this specific question, but other studies have reported the results of the ALLHAT trial.

Note: The exact details of the ALLHAT study are not provided in the given evidence, but it is generally known that the doxazosin arm was stopped due to increased cardiovascular events.