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

Chapter 7

ASCOT Trial

Jesper Mehlsen

7.1 Introduction

One of the first randomized, placebo-controlled trials in hypertensive subjects [1] demonstrated that whereas treatment dramatically reduced mortality and the incidence of strokes, it did not prevent myocardial infarction. This paradox was confirmed by metaanalyses of randomized trials—all of which used standard diuretic and/or beta-blocker therapy—showing treatment effects similar to those predicted by prospective, observational studies on stroke incidence but not on the occurrence of coronary heart disease (CHD; 2). It has been speculated that adverse effects of the older antihypertensive drugs on serum lipids, glucose, and potassium could blunt the cardioprotection conferred by lowering of blood pressure.

7.2 Objectives

The rationale for the ASCOT study [3] was thus to answer the issue of whether a newer combination of antihypertensive agents, a dihydropyridine calcium channel blocker (CCB) and an angiotensin converting enzyme (ACE) inhibitor, would produce greater benefits in terms of reducing CHD events than the standard beta-blocker/diuretic combination. The second main issue of ASCOT was whether lipid lowering with a statin would provide additional beneficial effects in those hypertensive patients with average or below average levels of serum cholesterol.

7.3 Study Design

ASCOT involved two treatment comparisons in a factorial design—a prospective, randomized, open, blinded endpoint design comparing two antihypertensive ...