Methods and Applications of Statistics in Clinical Trials, Volume 1: Concepts, Principles, Trials, and Designs

Chapter 75

TNT Trial

John C. Larosa, Scott M. Grundy, and David D. Waters

75.1 Introduction

The link between elevated LDL-C levels and increased risk of coronary heart disease (CHD) events is well established. Indeed, for secondary prevention trials, the relationship between on-treatment LDL-C and CHD event, rates seems to be approximately linear [1]. Secondary prevention guidelines currently recommend an LDL-C treatment target of <100 mg/dL (<2.6 mmol/L) for patients with CHD or CHD equivalents (including clinical manifestations of noncoronary forms of atherosclerotic disease [peripheral arterial disease, abdominal aortic aneurysm, and carotid artery disease (transient ischemic attacks or stroke of carotid origin or >50% obstruction of a carotid artery)], diabetes, and 2+ risk factors with 10-year risk for hard CHD >20%) and state that it is reasonable to reduce LDL cholesterol levels to <70 mg/dL (1.8 mmol/L) in very high-risk patients [2,3]. However, prior to the Treating to New Targets (TNT) study. the value of treating CHD patients, particularly those with stable, nonacute disease, to LDL-C levels substantially below 100 mg/dL (2.6 mmol/L) had not been clearly demonstrated.

75.2 Objectives

The primary hypothesis of TNT was that reducing LDL-C levels to well below 100 mg/dL (2.6 mmol/L) in stable CHD patients with modest LDL-C elevation (despite previous low-dose atorvastatin therapy) could yield incremental clinical benefit [4,5]. This hypothesis was tested by comparing the ...