Therapeutic implications of escape from angiotensin-converting enzyme inhibition in patients with chronic heart failure

Abstract

The level of inhibition of the angiotensin-converting enzyme (ACE) provided by standard doses of ACE inhibitors may only be partial during long-term treatment in patients with severe chronic heart failure (CHF). Partial ACE inhibition with time is often referred to as escape from ACE inhibition and labeled ACE escape. Several lines of evidence suggest that ACE escape occurs in patients with severe CHF. Plasma levels of angiotensin II rise above initial values during long-term ACE inhibition, and the effects of ACE inhibitors on cardiac remodeling and lowering of sympathetic nervous system activity attenuate after 1 year of treatment. Moreover, angiotensin II type I receptor blockade (ARB) produces clinical and hemodynamic benefits in patients with CHF who are already receiving ACE inhibitors. The therapeutic implications of ACE escape include evaluation of higher- than-standard doses of ACE inhibitors and routine addition of ARB to ACE inhibition in patients with severe CHF. Data are reviewed to demonstrate that ACE escape reflects inadequate ACE dosage rather than a decrease in ACE inhibition occurring with time.

Isolation and Characterization of Bioactive Pro-Peptides with in Vitro Renin Inhibitory Activities from the Macroalga Palmaria palmata

“…These concentrations were selected due to previous studies where the IC 50 value for Z-Arg-Arg-Pro-Phe-His-Sta-Ile-His-Lys-(Boc)-OMe was obtained and also where this compound demonstrated >90% inhibition of renin at a concentration of 10 μmol/L. 20 In this study, Z-Arg-Arg-Pro-Phe-His-Sta-Ile-His-Lys-(Boc)-OMe, assayed at 10 μmol/L and 1 μmol/L, inhibited renin by 94.71% (±0.87) and 57.35% (±0.91), respectively, as shown in Figure 2.…”

Combined use of direct renin inhibitor and carvedilol in heart failure with preserved systolic function

“…The use of Angiotensin Converting Enzyme inhibitors (ACE-I) and Angiotensin Receptor Blockers (ARB) is associated with angiotensin-II and aldosterone escape [11][12][13]. The use of direct renin inhibitors (DRI) will help in better suppression of the Renin Angiotensin Aldosterone System (RAAS) activity.…”

Ace-Inhibitors Versus Angiotensin Receptor Blockers for Renoprotection : Conclusions From the Evidence and From the Evidence Behind the Evidence

“…Long-term treatment with ACE inhibitors leads to a gradual return of circulating angiotensin II concentrations to pre-treatment values, a phenomenon termed ACE escape (6). One explanation for this observation came…”