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

Chapter 24

Coronary Drug Project

Paul L. Canner

24.1 Introduction

By 1960, evidence had accrued that linked elevated blood lipid levels with increased incidence of coronary heart disease (CHD). At the same time, the pharmaceutical industry was developing drugs that were effective in reducing blood cholesterol in persons with hyperlipidemia. The time had come to assess whether reduction of lipid levels would be effective in the treatment and possible prevention of CHD. In November 1960, proceedings were started that culminated in a line item in the Federal budget for funding in 1966 of the Coronary Drug Project (CDP) [1].

24.2 Objectives

The CDP was a randomized, double-blind, placebo-controlled clinical trial of the efficacy and safety of five lipid-modifying agents in men with previous myocardial infarction (MI) [2]. The patients were followed for a minimum of 5 years to determine whether pharmaceutical modification of blood lipids would lead to improved survival and a reduction in cardiovascular (CV) mortality and morbidity. A secondary objective was to identify baseline prognostic factors for CV mortality and morbidity in the placebo group of patients.

24.3 Study Design and Methods

24.3.1 Treatments

CDP patients were randomly allocated to six treatment arms: mixed conjugated equine estrogens at two dosage levels (2.5 and 5.0 mg/day), clofibrate (1.8 g/day), dextrothyroxine (6.0 mg/day), nicotinic acid (or niacin, 3.0 g/day), and a lactose placebo (3.8 g/day) [2]. These treatments ...