Heart failure: future treatment approaches

Large-scale clinical trials of vasodilators with nitrates and hydralazine and with angiotensin-converting enzyme (ACE) inhibitors in the 1980s and early 1990s provided the first credible evidence that medical therapy can prolong survival in patients with chronic heart failure (CHF). Moreover, patients treated with ACE inhibitors required fewer hospitalizations for worsening heart failure (HF). Nonetheless, the prognosis in patients with HF remains bleak, and better therapies are urgently needed. Recently, beta-blockers and spironolactone have been shown to reduce mortality when added to ACE inhibitors, diuretics, and digoxin. Digoxin has a neutral effect on overall mortality but does reduce the rate of hospitalization. Angiotensin II receptor blockers (ARB) inhibit the AT1 angiotensin receptor, which mediates the deleterious effects of the renin-angiotensin system, and may provide advantages over ACE inhibitors or advantages when used in combination with ACE inhibitors. Newer drugs that interfere with other mechanisms that contribute to progression of heart failure are also under study. As new therapies prove effective in large populations, they lead to a mandate for polypharmacy. The long-term solution to this clinical problem is to develop sensitive and reliable markers that can predict response in individual patients or monitor effectiveness of therapy.