Blood-Pressure Lowering in Intermediate-Risk Persons without Cardiovascular Disease

Linh Bao Nguyen, Mercer University College of Pharmacy


The Eighth Joint National Committee (JNC 8) guideline recommends initiating treatment when blood pressure is higher than 150/90 for patients older than 60. Initiating treatment is recommended for patients younger than 60 when either systolic is higher than 140 or diastolic is higher than 90. Treatment is not recommended when blood pressure is less than 140/90. [1]

The American Society of Hypertension (ASH) recommends drug therapy for patients with blood pressures higher than 140/90. Patients with pre-hypertension are counseled to make lifestyle changes. [2]




Title: Blood-Pressure Lowering in Intermediate-Risk Persons without Cardiovascular Disease
Design Double-blind, randomized, placebo-controlled trial; N= 12,705
Objective To evaluate blood-pressure-lowering therapy with a fixed-dose combination of an angiotensin receptor blocker (ARB) and a thiazide diuretic in persons at intermediate cardiovascular risk
Study Groups Active-therapy (candesartan 16 mg + hydrochlorothiazide 12.5 mg per day) (n= 6,356); placebo (n= 6,349)
Methods Eligible patients will receive both active treatments for blood-pressure lowering and cholesterol lowering for four weeks. Patients with 80% or more compliance will be randomized to either take candesartan 16 mg plus hydrochlorothiazide 12.5 mg or placebos daily.
Duration April 2007 to November 2010
Primary Outcome Measure First co-primary outcome: composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke; second co-primary outcome: composite of resuscitated cardiac arrest, heart failure, and revascularization
Baseline Characteristics   Candesartan + hydrochlorothiazide (n= 6,356) Placebo (n= 6,349)
Age (years) 65.7 65.8
Female (%) 45.8 46.7
Systolic (mmHg) 138.2 137.9
Diastolic (mmHg) 82 81.8
Heart rate (beats/min) 72.9 72.5
Body mass index (kg/m2) 27.1 27.1
Waist-to-hip ratio (n) 0.94 0.94
Chinese (%) 29 29.1
Hispanic (%) 27.4 27.7
White (%) 20.2 19.9
South Asian (%) 14.7 14.5
Other Asian (%) 5.4 5.6
Black (%) 1.8 1.7
Other ethnic group (%) 1.6 1.5
Results   Candesartan + hydrochlorothiazide (n= 6,356) Placebo (n= 6,349) Hazard ratio (95% CI) p value
First co-primary outcome (%) 4.1 4.4 0.93 (0.79-1.10) 0.40
Second co-primary outcome (%) 4.9 5.2 0.95 (0.81-1.11) 0.51
Adverse Events Common Adverse Events: N/A
Serious Adverse Events: hypotension, dizziness, or light-headedness 3.4%; renal dysfunction or abnormalities in serum potassium level 0.5%
Percentage that Discontinued due to Adverse Events: 24.4% in active-therapy group
Study Author Conclusions Therapy with candesartan at a dose of 16 mg per day plus hydrochlorothiazide at a dose of 12.5 mg per day was not associated with a lower rate of major cardiovascular events than placebo among persons at intermediate risk who did not have cardiovascular disease.


This study supports the recommendations from JNC8 and ASH for not treating patients when blood pressure is less than 140/90. The study was completed with ethnically diverse population. Therefore, this recommendation is also valid for other ethnic groups besides Caucasian, such as, Chinese, Hispanic, and South Asian.



  1. James PA, Oparil S, Carter BL, et al. 2014 evidence-based guideline for the management of high blood pressure in adults. Report from the panel members appointed to the Eighth Joint National Committee (JNC 8). JAMA 2013 Dec 18. doi: 10.1001/jama.2013.284427.
  2. Weber MA, Schiffrin EL, White WB, et al. Clinical practice guidelines for the management of hypertension in the community: a statement by the American Society of Hypertension and the International Society of Hypertension. J Clin Hypertens (Greenwich). 2014;16(1):14-26.
  3. Lonn EM, Bosch J, López-jaramillo P, et al. Blood-Pressure Lowering in Intermediate-Risk Persons without Cardiovascular Disease. N Engl J Med. 2016;374(21):2009-20.


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