Calcium channel antagonists (CCAs) may either be divided into the 
dihydropyridines (e.g. amlodipine, felodipine, isradipine, lacidipine, 
nilvadipine, nifedipine, nicardipine etc.), the phenylalkylamines (e.g. 
verapamil) and the benzothiazepines (e.g. diltiazem) according to their chemical 
structure, or into first generation agents (nifedipine, verapamil and diltiazem) 
and second generation agents (subsequently developed 
dihydropyridine-derivatives). Second generation CCAs are characterized by 
greater selectivity for calcium channels in vascular smooth muscle cells than 
the myocardium, a longer duration of action and a small trough-to-peak variation 
in plasma concentrations. Heart failure is characterized by decreased cardiac 
output resulting in inadequate oxygen delivery to peripheral tissues. Although 
the accompanying neurohormonal activation, leading to vasoconstriction and 
increased blood pressure, is initially beneficial in increasing tissue 
perfusion, prolonged activation is detrimental because it increases afterload 
and further reduces cardiac output. At the level of the myocyte, heart failure 
is associated with increased intracellular calcium levels which are thought to 
impair diastolic function. These changes indicate that the CCAs would be 
beneficial in patients with heart failure. There has been a strong interest and 
increasing experience in the use of CCAs in patients with heart failure. Despite 
potential beneficial effects in initial small trials, findings from larger 
trials suggest that CCA may have detrimental effects upon survival and 
cardiovascular events. However, this may not necessarily be a 'class b' effect 
of the CCAs as there is considerable heterogeneity in the chemical structure of 
individual agents. Clinical experience with different CCAs in patients with 
heart failure includes trials that evaluated their effects on hemodynamic 
parameters, exercise tolerance and on symptomatology. However, the most relevant 
results are those from randomized clinical trials that assessed mortality as the 
primary endpoint. First generation CCAs have direct negative inotropic effects 
and even sustained release formulations have not proved any beneficial effect 
upon survival. With second generation CCAs, some benefit on hemodynamic 
parameters has been observed but none on survival, alone or in combination with 
ACE inhibitors. It is noteworthy that although amlodipine had a neutral effect 
on morbidity and mortality in large, randomized, placebo-controlled trials in 
patients with heart failure, the drug was well tolerated. There is no specific 
indication for CCAs (first or second generation) in patients with systolic heart 
failure, alone or in combination with ACE inhibitors, but amlodipine may be a 
considered in the management of hypertension or coronary artery disease in 
patients with heart failure.