The evolution of heart failure management over recent decades: from CONSENSUS to CIBIS

The treatment of chronic heart failure (CHF) has changed greatly during the last two decades, moving from therapy based on a haemodynamic model to treatments targeting the neuroendocrine systems and the remodelling process. The use of inotropic agents to compensate for the loss of contractile force resulted only in neutral or deleterious effects on long-term prognosis. Vasodilator therapy was then introduced with the objective of improving haemodynamics and reducing cardiac load. The first vasodilator studied, hydralazine/isosorbide dinitrate, was rapidly superseded by the ACE-inhibitors, the first neurohormonal antagonists to demonstrate mortality reduction in CHF, and to inhibit left ventricular (LV) remodelling. During the 1980s, ACE-inhibitors were shown to benefit patients in all NYHA classes including patients with asymptomatic LV dysfunction. The concept of neurohormonal blockade was then extended to the sympathetic nervous system. Although the first evidence of a beneficial effect of beta-blockade dates back as early as 1975, it was not until the 1990s that major randomized controlled trials showed a mortality reduction of approximately one-third when beta-blockers were given in addition to standard therapy with ACE-inhibitors and diuretics. In recent years, the aldosterone antagonists have also emerged as beneficial treatments for severe CHF. However, other neurohormonal antagonists have proved disappointing. Most recently, cardiac resynchronization therapy, with or without an implantable cardioverter defibrillator, has also been shown to reduce morbidity and mortality in selected patients. With the range of drugs and devices now available, the challenge now is to find the optimal combination for each patient.