The Valsartan Antihypertensive Long-term Use Evaluation Trial

VALUE was a multicenter, prospective, double-blinded randomized clinical trial initiated and led by the investigators. The study took place from 1997 to 2004. The sponsor was Novartis, who had an interactive role with the investigators for the study design, and Novartis monitored study sites and provided source data verifications. In 2011, Ullevaal University Hospital, Oslo, Norway, took over the database with conditions detailed in a written agreement with the funder. One author (S.E.K.) had from then full access to all the data and took responsibility for its integrity and the data analysis. Thus, the data file resides in the hands of the authors, and Novartis had no role in the present study.

The trial was approved by ethics committees and written informed consent collected from all the participants in 31 countries.

The study compared, in a prospective, randomized double-blinded design, the effects of two different antihypertensive treatment regimens on cardiac morbidity and mortality in hypertensive patients aged 50 years or older. One regimen was based on the ARB valsartan, and the other on the CCB amlodipine.

VALUE participants were selected based on predefined combinations of risk factors, including age, male gender, and the presence of certain conditions such as electrocardiographic left ventricular hypertrophy (ECG-LVH), determined by Cornell voltage-duration product or Sokolow-Lyon voltage criteria with or without a strain pattern, serum creatinine ≥150 μmol/l, proteinuria (positive dipstick in morning urine at two different visits), diabetes mellitus (DM), or verified coronary, cerebrovascular, or peripheral artery disease.

Exclusion criteria included pregnancy, renal artery stenosis, either myocardial infarction, percutaneous coronary intervention, or coronary artery bypass surgery during last three months, medically relevant valvular disease, cerebrovascular events last 3 months, severe hepatic disease, severe chronic kidney failure (serum creatinine >3.0 mg/dl, >265 µmol/L), congestive heart failure requiring angiotensin converting enzyme inhibitor and patients using beta-blocker for both coronary artery disease and hypertension.