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REVIEW ARTICLE

Surrogate end points in heart failure

Inder S. Anand, MD, FRCP, DPhil (Oxon), FACC^*,*, Viorel G. Florea, MD, PhD, DSc^* and Lloyd Fisher, PhD, FACC

^* University of Minnesota Medical School and Veterans Affairs Medical Center, Minneapolis, Minnesota, USA
Department of Biostatistics, University of Washington, Seattle, Washington, USA

Manuscript received December 27, 2000; revised manuscript received January 31, 2002, accepted February 6, 2002.

^* Reprint requests and correspondence: Professor Inder S. Anand, Director of Heart Failure Program, Veterans Affairs Medical Center, One Veterans Drive 111-C, Minneapolis, Minnesota 55417, USA.
anand001{at}tc.umn.edu

Because of the increasing number of pharmacologic strategies available for treatment of heart failure (HF), the time has come to reassess the adequacy of end points used to evaluate therapeutic efficacy. Interest in the use of surrogate end points in clinical studies is increasing. A surrogate end point is defined as a measurement that can substitute for a true end point for the purpose of comparing specific interventions or treatments in a clinical trial. A true end point is one that is of clinical importance to the patient (e.g., mortality or quality of life), whereas a surrogate end point is one biologically closer to the disease process (e.g., ejection fraction or left ventricular volume in HF). The prime motivation for the use of a surrogate end point concerns the possible reduction in sample size or trial duration. Such reductions have important cost implications and in some cases may influence trial feasibility. Another, perhaps more important, aspect of measuring surrogate end points is that they increase our understanding of the mechanism of action of drugs and thus may help physicians to take a more enlightened approach in managing their patients. In this article we have analyzed the possible potentials of the surrogate end points in clinical studies of patients with chronic HF. Other uses of possible surrogates are discussed, and the limitations in finding true surrogates are mentioned. At this time we conclude there is no well established surrogate in HF.

Abbreviations and Acronyms   BEST   Beta-blocker Evaluation of Survival Trial   BNP   brain natriuretic peptide   CONSENSUS   Cooperative North Scandinavian Enalapril Survival Study   EF   ejection fraction   FDA   Food and Drug Administration   HF   heart failure   LV   left ventricular/ventricle   MOXCON   Effect of Sustained Release Moxonidine on Mortality and Morbidity in Patients with Congestive Heart Failure   NE   norepinephrine   NYHA   New York Heart Association   Peak VO2   maximal oxygen intake   PRIME II   Second Prospective Randomized Study of Ibopamine on Mortality and Efficacy   PROMISE   Prospective Randomized Milrinone Survival Evaluation trial   QOL   quality of life   REFLECT   Randomized Evaluation of FLosequinan on ExerCise Tolerance   SAVE   Survival And Ventricular Enlargement trial   Val-HeFT   Valsartan Heart Failure Trial   V-HeFT   Vasodilator-Heart Failure Trial

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