What were the findings of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT)?

From the Guidelines

The ALLHAT study found that diuretics, such as chlorthalidone, are equally effective or superior to other antihypertensive medications, including calcium antagonists, ACE inhibitors, and α-blockers, in preventing primary and secondary outcomes in hypertensive patients. The study's results, as reported in the Journal of the American Society of Nephrology in 2004 1, highlight the importance of diuretics as initial drug therapy in treating hypertension.

Key Findings

• The ALLHAT study compared the effectiveness of a diuretic with other antihypertensive medications, including a calcium antagonist, an ACE inhibitor, and an α-blocker.
• The results showed that a diuretic was equally effective in primary outcomes and superior in some secondary end points compared to the other medications.
• The study's findings support the use of diuretics as initial therapy for hypertensive patients, due to their effectiveness in reducing blood volume and vascular resistance while having beneficial effects on arterial compliance.

Clinical Implications

• The ALLHAT study's results have significant implications for clinical practice, as they demonstrate that less expensive diuretics are as effective as newer, more costly medications for hypertension management.
• The study's findings continue to influence hypertension treatment guidelines, with thiazide diuretics, such as chlorthalidone, recommended as initial therapy for most patients with uncomplicated hypertension 1.

From the Research

Overview of the ALLHAT Study

The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) was a randomized, double-blind, active-controlled clinical trial that compared the effectiveness of different antihypertensive medications in preventing cardiovascular disease outcomes. The study found that:

• Chlorthalidone, amlodipine, and lisinopril were equally effective in preventing the primary outcome of fatal coronary heart disease or nonfatal myocardial infarction 2, 3
• Chlorthalidone and lisinopril were more effective at preventing heart failure, whereas amlodipine and chlorthalidone were more effective than lisinopril at preventing stroke 2
• Thiazide-type diuretics, such as chlorthalidone, were superior in preventing one or more major forms of cardiovascular disease and were less expensive 3

Comparison of Treatment Outcomes

The study compared the outcomes of participants randomized to chlorthalidone, amlodipine, or lisinopril, and found that:

• There were no significant differences between the treatment groups in terms of the primary outcome of combined fatal coronary heart disease or nonfatal myocardial infarction 3
• Amlodipine had a higher 6-year rate of heart failure compared to chlorthalidone, while lisinopril had higher 6-year rates of combined cardiovascular disease, stroke, and heart failure compared to chlorthalidone 3
• Chlorthalidone decreased systolic blood pressure to a slightly greater extent than amlodipine or lisinopril 4

Stroke Outcomes

The study also examined stroke outcomes among participants randomized to chlorthalidone, amlodipine, or lisinopril, and found that:

• Stroke rates were higher with lisinopril than with chlorthalidone or amlodipine in-trial, but not including post-trial 5
• In-trial differences in stroke rates were driven by race and gender, with lisinopril being less effective in preventing stroke among Blacks and women 5
• No treatment differences in stroke outcomes were detected over the 10-year period, and no differences appeared among treatment groups in adjusted risk of all-cause mortality including post-trial for participants with nonfatal in-trial strokes 5

Key Findings

The key findings of the ALLHAT study include:

• Thiazide-type diuretics, such as chlorthalidone, are effective in preventing cardiovascular disease outcomes and are less expensive than other antihypertensive medications 2, 3
• Amlodipine and lisinopril had higher rates of certain cardiovascular disease outcomes, such as heart failure and stroke, compared to chlorthalidone 3, 5
• The study's findings support the use of thiazide-type diuretics as first-line therapy for hypertension, particularly in high-risk patients 2, 3