What is the optimal angiotensin-converting enzyme inhibitor dose in heart failure?

Doses of angiotensin-converting enzyme (ACE) inhibitors used in the landmark heart failure trials that demonstrated survival benefit are rarely reached in routine practice. The authors review the current literature regarding optimal dosing of ACE inhibitors in heart failure with specific focus on neurohormonal, functional capacity, and clinical outcomes. Neurohormonal studies have shown that lower ACE inhibitor dosing may provide inadequate suppression of the renin-angiotensin-aldosterone system. Higher doses of ACE inhibitors have resulted in greater increments in exercise and functional capacity. Clinically, patients on high-dose ACE inhibitor therapy had significant reductions in all-cause mortality or hospitalization, cardiovascular hospitalizations, and heart failure-specific hospitalizations. There is, however, conflicting evidence, and so continued uncertainty exists regarding optimal dosing. Despite underutilization of ACE inhibitors, there is insufficient evidence to support lower doses. Likewise, limited data exist for doses higher than those used in the landmark trials. Clinicians should therefore attempt to reach target doses in heart failure whenever possible.