Funded Research

Medicine

The HOPE-3 (Heart Outcomes Prevention Evaluation) study

Funding Agency: The Population Health Research Institute at McMaster University, Canada
Study Design: Randomized, Double-Blind, Placebo Control, Factorial Assignment, Safety/Efficacy Study
Intervention: Rosuvastatin, Candesartan/Hydrochlorothiazide, Factorial vs. placebo
Duration of Study: 7 years (May 2007- October 2015)
Number of Patients: 12,705 Patient Populations: Cardiovascular Disease, Stroke, Asymptomatic individuals at moderate risk for CV events
Principal Investigator: Dr SP Kalantri, Director- Professor of Medicine
Ethics Approval: Obtained from Institutional Ethics Committee, MGIMS (MGIMS/IEC/ MS/154/2008 dated 07/05/2008)

Of the approximately 16 million people who die from heart disease and stroke annually, about half have no warning symptoms or previous incidence of cardiovascular disease. It is well known that lowering blood pressure and reducing cholesterol levels are two highly effective strategies to prevent heart disease and stroke, but the benefits of these interventions have only been studied in people who have traditionally-defined high blood pressure and cholesterol levels. However, most heart attacks and strokes occur in people who are considered to have normal blood pressure and cholesterol levels.

HOPE-3 is a large, simple trial evaluating the effects of lipid modification and blood pressure lowering and their combination in a wide range of middle aged people, who are at average risk for vascular events. HOPE-3 tested the concept of whether or not we can slow down, or better yet, reverse the process in most people before they develop cardiovascular disease. The trial randomized 12,705 women 60 years or older and men 55 years or older from 21 countries without known heart disease or prior stroke and without a clear indication or contraindication to any of the study medications. The department of Medicine at MGIMS was one of the centers that recruited eligible and consenting individuals from villages around Sevagram for the trial. Participants were randomly assigned to a fixed combination of candesartan (16 mg per day) and hydrochlorothiazide (12.5 mg per day) or placebo and to rosuvastatin (10 mg per day) or placebo. The rates of heart attacks, strokes, deaths and other cardiovascular events were compared between subjects receiving the active drugs and those on placebo. The median follow-up was 5.6 years.

The primary results of the Heart Outcomes Prevention Evaluation (HOPE)–3 trial were reported in three articles in the New England Journal of Medicine. (N Engl J Med 2016; 374:2021-2031; N Engl J Med 2016; 374:2032-2043 and N Engl J Med 2016; 374:2009-2020).

The study showed that rosuvastatin at a dose of 10 mg per day is more effective in preventing cardiovascular events than is candesartan at a dose of 16 mg per day plus hydrochlorothiazide at a dose of 12.5 mg per day in a relatively low-risk population. The study results provide support for the use of statins as a safe and effective intervention to prevent cardiovascular events in such patients.

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