Randomized clinical trials on surrogate end points: are they useful for evaluating cardiovascular and renal disease protection in hypertension? The case for yes.

Hard end point studies represent the best available evidence for demonstrating the cardiovascular and renal protection that is achievable with a given treatment in hypertensive patients, yet properly designed end point studies require large cohorts of patients and long follow-up, are expensive, and do not provide any insight on the mechanisms that lead to the clinical manifestations. Studies that are based on the incidence of preclinical alterations, i.e., the surrogate end points, may circumvent these limitations provided that their relationship with the major cardiovascular events is scientifically proved. In this respect, among the many surrogate end points that are under investigation, left ventricular hypertrophy, microalbuminuria, and treatment-induced diabetes seem most promising for replacing the hard end points in view of their undisputed mechanistic relationship with the clinical events and of the mounting evidence indicating that from their changes it is possible to predict the clinical outcome of patients. In addition, the limited resources that are required to carry out this kind of investigations make them preferable to hard end point studies for anticipating the cardiovascular and renal benefit associated with the use of antihypertensive agents.