Obtaining Reliable Information from Randomized Controlled Trials in Congestive Heart Failure and Left Ventricular Dysfunction

Abstract

Chronic congestive heart failure (CHF) is a syndrome that is the end result of a number of different kinds of cardiac damage and compensatory mechanisms resulting in a variable prognosis. Patients usually have a high mortality rate, a high rate of morbid complications, and multiple severe symptoms. The high rates of morbidity and symptoms lead to limitations in daily activities and poor quality of life. The aim of therapy in such patients should therefore be not only the amelioration of symptoms and signs of CHF but also the prevention of morbidity, improvement in quality of life, and prolongation of survival. Because the clinical course in a particular patient is highly variable and unpredictable, the effect of a therapy can be reliably evaluated only if all sources of errors in this evaluation are minimized. In general, errors can be classified into those due to systematic biases and those due to random errors. In order to avoid a variety of systematic biases randomized double-blind controlled trials are essential. Such studies avoid biases in patient allocation, minimize imbalances at entry use of other therapy, and avoid biases in endpoint ascertainment. In this chapter, I will discuss the following issues:

• 1. The likely size of effect with currently available interventions.

• 2. Why randomized trials are essential in heart failure.

• 3. Why some of the trials should be much larger than those that have been conducted.

• 4. How some of the currently employed methods of analysis and reporting can be biased and can lead to misleading conclusions.

• 5. Why one may not be able to extrapolate from the effect of a particular agent on surrogate endpoints (such as exercise tolerance) to clinically relevant outcomes such as survival or morbidity.

• 6. How the framework of the trials and the data that are collected systematically provide an opportunity to learn more about the clinical course of patients with heart failure.

• 7. Examples of some large studies that are in progress.