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Doxazosin and congestive heart failure
1Department of Clinical Pharmacology, Medical College of Virginia of Virginia Commonwealth University, Richmond, VA 23298, USA. dsica@hsc.vcu.edu
Insights
Doxazosin, an antihypertensive drug, showed increased cardiovascular disease, mainly congestive heart failure, in the ALLHAT trial. It should now be considered a secondary or tertiary treatment option.
Area of Science:
- Cardiology
- Pharmacology
Background:
- Doxazosin is a widely prescribed antihypertensive medication.
- Recent findings from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) have raised concerns regarding its use.
Purpose of the Study:
- To evaluate the efficacy and safety of doxazosin compared to other antihypertensive agents in high-risk patients.
- To assess the primary outcome of fatal coronary heart disease and nonfatal myocardial infarction.
Main Methods:
- The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) was a large, simple clinical trial.
- It compared chlorthalidone (diuretic) with amlodipine (calcium-channel blocker), lisinopril (ACE inhibitor), and doxazosin (alpha-blocker) in hypertensive patients aged 55 years or older.
Main Results:
- Doxazosin was withdrawn from the ALLHAT trial due to interim analysis.
- An interim analysis revealed a 25% increase in combined cardiovascular disease in patients on doxazosin compared to chlorthalidone.
- This increase was primarily driven by a higher incidence of congestive heart failure.
Conclusions:
- The ALLHAT findings indicate a potential increased risk of cardiovascular events, particularly heart failure, with doxazosin.
- Clinicians should carefully consider these results, viewing doxazosin as a secondary or tertiary antihypertensive therapy.
- Further comprehensive review of the ALLHAT data is warranted before definitive clinical practice changes are made.
Abstract:
Doxazosin remains a commonly used antihypertensive medication, although its use has been tainted by recent findings from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). ALLHAT was a large, simple trial, designed in a fashion to closely mimic clinical practice as it occurs in high-risk hypertensive patients aged 55 years or older. Its goals were to determine whether the incidence of the primary outcome--a composite of fatal coronary heart disease and nonfatal myocardial infarction--differed between treatment with a diuretic (chlorthalidone) (12.5-25.0 mg/day) and treatment with each of three other types of antihypertensive drugs-a calcium-channel blocker (amlodipine), an angiotensin-converting enzyme inhibitor (lisinopril), and a peripheral alpha-adrenergic blocker (doxazosin) (2-8 mg/day). Doxazosin was recently withdrawn from this trial after an interim analysis showed the secondary end point of combined cardiovascular disease to be 25% greater in patients on doxazosin than in those assigned to treatment with chlorthalidone. This finding was largely driven by congestive heart failure. The practicing clinician should not abandon doxazosin completely because of the ALLHAT findings, although these findings are indisputably important. These results represent an interim analysis and their application to clinical practice needs to occur carefully. A valued member of our therapeutic armamentarium need not be laid entirely to rest; rather, doxazosin should now be viewed as a secondary or tertiary antihypertensive therapy pending a more complete review of the ALLHAT data.