Problem Hypertension in High-Risk Patients
Format Multicenter, double-blind clinical trial
Treatment Benazepril plus amlodipine
Control Benazepril plus hydrochlorothiazide
Population 11,506 patients
Inclusion criteria Hypertensive individuals at high risk over 60 years old
-With systolic BP 160 mm Hg or currently on antihypertensive therapy
-AND Evidence of cardiovascular or renal disease or target organ damage (see below)

Patients aged 55 to 59 years were eligible if they have evidence of two or more of the cardiovascular diseases or target organ damage criteria

Evidence of CV disease or end-organ damage included:
-Cardiac diseases (and of)
--Previous MI
--Hospitalization for unstable angina
--Previous revascularisation
-Previous stroke
-Previous peripheral arterial occlusive disease
-Renal impairment (Creat > 133 or macroalbuminuria)

Men or women of any ethnic background were eligible to be enrolled.
Exclusion criteria Current evidence for angina pectoris (specifically, any symptom within 3 months before evaluation for study entry)
History of symptomatic heart failure or evidence of left ventricular ejection fraction 40%
Myocardial infarction
Other acute coronary syndromes, or coronary revascularizations within 1 month of the first visit
Stroke or other ischemic cerebrovascular episodes within 3 months preceding study evaluation
Hypertension that is excessively severe, known to be refractory to treatment, or known to have a secondary cause

In addition, any other concomitant illness, physical impairment, or mental condition that could interfere with the effective conduct of the study during its likely duration also served as an exclusion criterion
Follow-up Mean 35.6 months
Primary endpoint Time to composite of a cardiovascular event and death from cardiovascular causes
Secondary endpoint(s) Composite of cardiovascular events, defined as the primary end point excluding fatal events
Composite of death from cardiovascular causes, nonfatal stroke, and nonfatal myocardial infarction
Individual components of the primary and secondary end points
Hospitalization for heart failure
Death from any cause

Prespecified subgroup analyses based on age, sex, and presence or absence of diabetes were also performed
Details -
Brief summary: CCBs are superior to diuretics when added to ACEi in high risk patients
PAPER: Benazepril plus Amlodipine or Hydrochlorothiazide for Hypertension in High-Risk Patients
Date 4 Dec 2008
Journal N Engl J Med. 2008 Dec 4;359(23):2417-28.
Information Benazepril-amlodipine superior to the Benazepril-hydrochlorothiazide in high risk HTN patients
-Reduced CV events and death from CV events
-Similar BP reductions (difference < 1 mmHg)
-Overall primary end point was not driven by any one outcome

Note this may appear at odds with ALLHAT
-?Different diuretic used
-?Benefits of CCB specifically when RAS inhibited
PAPER: Effects of body size and hypertension treatments on cardiovascular event rates: subanalysis of the ACCOMPLISH randomised controlled trial
Date 6 Dec 2012
Journal Lancet. 2012 Dec 5. pii: S0140-6736(12)61343-9.
Information Thiazides appear less effective in obese patients
CCBs appear to benefit all subgroups