Problem Hypertension with cardiac RFs
Format Multicenter, double-blind, randomized trial
Treatment Chlorthalidone OR Amlodipine OR Lisinopril
Control -
Population 33,357 patients
Inclusion criteria > 55 years old

Stage 1 or stage 2 hypertension
-Untreated hypertension with SBP 140–180 mmHg or DBP 90–110 mmHg
--But not higher than SBP 180 mmHg or DBP 110 mmHg]
-Or treated with 1–2 antihypertensive drugs and BP ≥ 160/100 at visit 1 or ≥180/110 mm Hg at visit 2, when medication may have been partially withdrawn

At least one additional risk factor for coronary heart disease (CHD)
-Previous (>6 months) myocardial infarction or stroke
-Left ventricular hypertrophy demonstrated by electrocardiography or echocardiography
-History of type 2 diabetes
-Current cigarette smoking
-High-density lipoprotein cholesterol of less than 35 mg/dL (<0.91 mmol/L)
-Documentation of other atherosclerotic CVD
Exclusion criteria History of hospitalized or treated symptomatic heart failure (HF) and/or known left ventricular ejection fraction of less than 35%
Follow-up Mean 4.9 years
Primary endpoint Composite of fatal coronary heart disease (CHD) or nonfatal myocardial infarction (MI)
Secondary endpoint(s) All-cause mortality
Combined CHD & nonfatal MI, CHD death, coronary revascularization, hospitalized angina
Combined cardiovascular disease & combined CHD, stroke, lower extremity revascularization, treated angina, fatal/ hospitalized/treated congestive heart failure, hospitalized or outpatient peripheral arterial disease
Other – renal
Details N.B. 42,418 patients were randomised, but the doxazosin arm of 9,062 patients was discontinued early at 3.3 years.

Unless the drug regimen had to be tapered for safety reasons, individuals continued any prior antihypertensive medications until they received randomized study drug, at which point they stopped taking all previous medications.
Brief summary: Similar control with CCB/Thiazide/ACEi; Thiazide may be superior. Doxazosin less suitable. Monotherapy often not sufficient.
PAPER: Major Outcomes in High-Risk Hypertensive Patients Randomized to Angiotensin-Converting Enzyme Inhibitor or Calcium Channel Blocker vs Diuretic
Date 18 Dec 2002
Journal JAMA. 2002 Dec 18;288(23):2981-97.
Information Chlorthalidone vs. Amlodipine vs. Lisinopril in high-risk HTN patients
-No difference in fatal/non-fatal CHD/MI
-Chlorthalidone lead to better control of SBP
--1 mm lower vs. amlodipine; 2 mm lower vs. lisinopril
--Reduced stroke, combined CVD, HF (vs. Lisinopril)
--Reduced HF (vs. Amlodipine)

Only 30% of patients achieve <140/90 on monotherapy

N.B. Doxazosin arm stopped early
-25 percent higher rate of combined CVD
-Two-fold higher rate of heart failure vs. Chlorthalidone