(a) Davis BR, Cutler JA, Gordon DJ, Furberg CD, Wright JT Jr, Cushman WC, Grimm RH, LaRosa J, Whelton PK, Perry HM, Alderman MH, Ford CE, Oparil S, Francis C, Proschan M, Pressel S, Black HR, Hawkins CM
(b) ALLHAT Officers and Coordinators(c) Pressel SL, Davis BR, Wright JT, Geraci TS, Kingry C, Ford CE, Piller LB, Bettencourt J, Kimmel B, Lusk C, Parks H, Simpson LM, Nwachuku C, Furberg CD (d) and (e) ALLHAT Officers and Coordinators

(a) Rationale and design for the Antihypertensive and Lipid Lowering treatment to prevent Heart Attack Trial (ALLHAT)
(b) Major cardiovascular events in hypertensive patients randomized to doxazosin vs chlorthalidone. The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT)
(c) Operational aspects of terminating the doxazosin arm of the Antihypertensive and Lipid Lowering treatment to prevent Heart Attack Trial (ALLHAT)
(d) Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic
(e) Major outcomes in moderately hypercholesterolemic, hypertensive patients randomized to pravastatin vs usual care

(a) Am J Hypertens 1996;9:342-60
(b) JAMA 2000;283:1967-75
(c) Control Clin Trials 2001;22:29–41
(d) JAMA 2002;288:2981–97
(e) JAMA 2002;288:2998–3007

Hypertension and hypercholesterolaemia

Antihypertensive arm: to assess the incidence of fatal coronary heart disease and nonfatal MI in patients treated with chlorthalidone, amlodipine, lisinopril, or doxazosin Lipid-lowering arm: to assess the all-cause mortality in patients treated with either pravastatin or ‘usual care’

Antihypertensive arm: randomised, double-blind. Lipid-lowering arm: randomised, open

Antihypertensive arm: mean 4.9 years Lipid-lowering arm: mean 4.8 years

Antihypertensive arm: 33,357 (15,255 chlorthalidone, 9048 amlopidine, 9054 lisinopril), aged ≥ 55 years, with hypertension and at least 1 other risk factor for coronary heart disease Lipid-lowering arm: 10,355 patients (5170 pravastatin, 5185 usual care), aged ≥ 55 years, with fasting LDL cholesterol 3.1–4.9 mmol/l for those with no known coronary heart disease, or 2.6–3.3 mmol/l for those with known coronary heart disease, and fasting triglyceride levels < 3.9 mmol/l, selected from the antihypertensive arm

Antihypertensive arm: chlorthalidone, 12.5–25 mg, or amlodipine, 2.5–10 mg, or lisinopril, 10–40 mg, or doxazosin, 2–8 mg (discontinued early) Lipid-lowering arm: pravastatin, 40 mg in the evening plus NCEP diet, or NCEP diet alone

Step 2 and step 3 antihypertensive agents, if required

Antihypertensive arm: primary combined outcome of fatal coronary heart disease or nonfatal MI occurred in 2956 patients. No significant difference was observed for amlodipine (relative risk 0.98, 95% CI 0.90–1.07; p = 0.65) or lisinopril (relative risk 0.99, 95% CI 0.91–1.08; p = 0.81) vs chlorthalidone Lipid-lowering arm: all-cause mortality did not differ significantly between the pravastatin and usual care treatment groups (relative risk 0.99, 95% CI 0.89–1.11; p = 0.88)

After an interim analysis, in March 2000 an independent review committee recommended discontinuing the doxazosin-treatment arm because of a higher incidence of combined cardiovascular events, and in particular congestive heart failure events, for the doxazosin group compared to the chlorthalidone group

This study has been the basis for a number of publications. A selection of references:

Angio-oedema
– Piller LB et al, J Clin Hypertens 2006;8:649–56

Antihypertensive medication at entry
– Grimm RH et al, J Clin Hypertens 2009;11:466–74

Antihypertensive medication in the long term
– Cushman W et al, Circulation 2010;120:2160

Atrial fibrillation
– Haywood LJ et al, J Am Coll Cardiol 2009;54:2023–31

Combination therapy
– Cushman WC et al, J Clin Hypertens 2008;10:751–60

Cost-effectiveness
– Heidenreich PA et al, J Gen Intern Med 2008;23:509–16

Diuretics and fasting glucose levels
– Barzilay JI et al, Arch Intern Med 2006;166:2191–201

Diuretics and prevention of heart failure
– Davis BR et al, Circulation 2006;113:2201–10
– Davis BR et al, Circulation 2008;118:2259–67

Diuretics vs alpha-blockers
– ALLHAT Officers and Coordinators, Hypertension 2003;42:239–46

Genetics of hypertension (GenHAT)
– Maitland-van der Zee AH et al, Pharmacogenet Genomics 2008;18:651–6
– Lynch AI et al, Pharmacogenet Genomics 2009;19:415–21

Metabolic syndrome
– Black HR et al, Diabetes Care 2008;31:353–60

Race
– Wright JT Jr et al, Arch Intern Med 2008;168:207–17
– Margolis KL et al, Am Heart J 2009;158:948–55

Renal outcomes and glomerular filtration rate
– Rahman M et al, Arch Intern Med 2005;165:936–46
– Rahman M et al, Am J Kidney Dis 2008;52:412–24