Clinical characteristics of vesnarinone

Congestive heart failure is a common condition with a poor prognosis. Its high rates of morbidity and mortality produce a huge societal burden. Current pharmacological treatment approaches are based on angiotensin-converting enzyme inhibitors, diuretics and digoxin, but up to 5% of patients may have refractory disease with persistent symptoms at rest. Such patients with advanced-stage disease may be candidates for treatment with the novel agent vesnarinone, a mixed phosphodiesterase inhibitor and ion-channel modifier that has modest, dose-dependent, positive inotropic activity, but minimal negative chronotropic activity. Vesnarinone improves ventricular performance most in patients with the worst degree of heart failure. However, before the initiation of vesnarinone therapy, risk-benefit profiles in individual patients should be considered, because in two large-scale studies [i.e. of the high dosage used in the Vesnarinone Study Group Trial (VSGT), and of both dosages used in the Vesnarinone Trial (VEST)] a dose-dependent increase in mortality was identified for vesnarinone 30-120 mg/day. The two studies also found significant vesnarinone-induced, short-term improvements in quality of life (QOL) in patients with refractory end-stage heart failure. Such patients are the most willing to trade-off a slightly increased risk of mortality for improved QOL. It is thus in these patients with refractory end-stage heart failure that vesnarinone may ultimately establish an important treatment role. However, detailed further investigation of the overall place of vesnarinone in heart failure management, with particular reference to the clinical potential of vesnarinone plus beta-blocker combination therapy, for example, is certainly warranted.