Endpoints in clinical trials: does evidence only originate from 'hard' or mortality endpoints?

Abstract

'Hard' primary endpoints from randomized clinical trials, such as cardiovascular morbidity and mortality data are usually considered as the backbone of evidence for clinical practice guidelines. However, 'intermediate' or 'surrogate' endpoints, for example, biological or imaging markers are increasingly being recognized for their importance in stratifying risk and determining treatment strategy in clinical practice. In hypertension, use of validated surrogate endpoints, notably left ventricular hypertrophy (LVH), microalbuminuria, arterial stiffness and carotid intima-media thickness are discussed. These variables are among those assessed in clinical practice, and are considered as predictors of cardiovascular risk. Moreover, some antihypertensive therapies can reverse these organ-damage abnormalities and improve cardiovascular prognosis partly independently from their blood pressure lowering effect. Recognizing the importance of identifying subclinical organ damage in the prediction of cardiovascular risk provides further support to physicians making decisions in their daily clinical practice and offers possibilities for prospective studies on cardiovascular prevention in populations of middle age with low cardiovascular risk. In this article we overview the advantages and disadvantages of morbidity/mortality trials and 'hard' versus 'soft' endpoints. We also considered the relevance of analyzing not only primary endpoints but also secondary endpoints.