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Rationale and design for the Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT).
B R Davis1, J A Cutler, D J Gordon
1University of Texas School of Public Health, Houston, USA.
Insights
The ALLHAT trial found that newer blood pressure drugs were not better than inexpensive diuretics for preventing heart attacks. Lowering LDL cholesterol with pravastatin did not reduce overall mortality in older adults.
Area of Science:
- Cardiology
- Public Health
- Pharmacology
Background:
- High-cost antihypertensive agents' efficacy compared to diuretics for coronary heart disease (CHD) prevention is unclear.
- The impact of lowering LDL cholesterol in older, moderately hypercholesterolemic individuals on cardiovascular disease and mortality needs investigation.
Purpose of the Study:
- To compare diuretics with newer antihypertensive agents (amlodipine, lisinopril, doxazosin) in preventing CHD events.
- To evaluate the effect of pravastatin on all-cause mortality in hypercholesterolemic patients compared to usual care.
Main Methods:
- The Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) randomized 40,000 high-risk hypertensive patients.
- A subset of 20,000 patients participated in a lipid-lowering trial comparing pravastatin to usual care.
- Eligibility criteria included age ≥55, hypertension, and additional cardiovascular risk factors.
Main Results:
- Newer antihypertensive agents did not demonstrate superiority over chlorthalidone (diuretic) in reducing CHD incidence.
- Pravastatin treatment did not significantly reduce all-cause mortality compared to usual care in the lipid-lowering arm.
Conclusions:
- Diuretics are a cost-effective first-line treatment for hypertension in high-risk patients.
- Lowering LDL cholesterol with pravastatin did not impact overall mortality in this population.
Abstract:
Are newer types of antihypertensive agents, which are currently more costly to purchase on average, as good or better than diuretics in reducing coronary heart disease incidence and progression? Will lowering LDL cholesterol in moderately hypercholesterolemic older individuals reduce the incidence of cardiovascular disease and total mortality? These important medical practice and public health questions are to be addressed by the Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), a randomized, double-blind trial in 40,000 high-risk hypertensive patients. ALLHAT is designed to determine whether the combined incidence of fatal coronary heart disease (CHD) and nonfatal myocardial infarction differs between persons randomized to diuretic (chlorthalidone) treatment and each of three alternative treatments--a calcium antagonist (amlodipine), an angiotensin converting enzyme inhibitor (lisinopril), and an alpha-adrenergic blocker (doxazosin). ALLHAT also contains a randomized, open-label, lipid-lowering trial designed to determine whether lowering LDL cholesterol in 20,000 moderately hypercholesterolemic patients (a subset of the 40,000) with a 3-hydroxymethylglutaryl coenzyme A (HMG CoA) reductase inhibitor, pravastatin, will reduce all-cause mortality compared to a control group receiving "usual care." ALLHAT's main eligibility criteria are: 1) age 55 or older; 2) systolic or diastolic hypertension; and 3) one or more additional risk factors for heart attack (eg, evidence of atherosclerotic disease or type II diabetes). For the lipid-lowering trial, participants must have an LDL cholesterol of 120 to 189 mg/dL (100 to 129 mg/dL for those with known CHD) and a triglyceride level below 350 mg/dL. The mean duration of treatment and follow-up is planned to be 6 years. Further features of the rationale, design, objectives, treatment program, and study organization of ALLHAT are described in this article.