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Observational studies in people without cardiovascular (CV) disease show a strong, graded association between blood pressure (BP) above 115/75 mmHg and CV risk. Most BP lowering trials included people with established CV disease, diabetes, renal disease and/or hypertension with end organ damage or in the absence of these conditions those with systolic BP above 160 mmHg. However, most CV events in populations arise from persons without these major risk factor and the role of BP lowering drugs among them is uncertain.

Design and method:

HOPE-3 was a double-blind randomized placebo-controlled trial with a 2-by-2 factorial design which evaluated BP lowering with candesartan/hydrochlorothiazide 16/12.5 mg/day, cholesterol lowering with rosuvastatin 10 mg/day and their combination in a population at moderate CV risk. We enrolled men older 55 years and women older 60 years with one or more risk factors, without selection based on history of hypertension or strict BP entry levels. Persons with clear indications or contraindications to any of the study drugs, including a history of CV disease, advanced renal disease or advanced diabetes were excluded. The two co-primary outcomes were the composite of CV death, nonfatal myocardial infarction or nonfatal stroke (tested at p < 0.04) and the composite of any of these events plus resuscitated cardiac arrest, heart failure and revascularizations (tested at p < 0.02). We projected a 1%/year placebo event rate and over 80% power to detect a relative risk reduction of at more 22.5% and accrual of more 500 first co-primary outcomes and 600 second co-primary outcomes.


We randomized 12,705 participants from 21 countries. Mean follow-up was 5.7 years. Compliance was high and less that 1% of participants were lost or refused follow up. Participants’ mean age was 65.6 years, 46% were women, mean BP was 138/82 mmHg. The safety of BP lowering treatment in this population and its effects on CV outcomes overall and in prospectively defined subgroups by baseline risk and BP levels were evaluated.


The HOPE-3 trial provide information on BP lowering in a population at moderate risk, without selection based on history of hypertension or elevated BP levels.

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