Although symptoms may improve in some patients within the first 48 hours of therapy with an ACE inhibitor, the clinical responses to these drugs are generally delayed and may require several weeks or months before becoming apparent. Even if symptoms do not improve, long-term treatment with an ACE inhibitor should be maintained to reduce the risk of death or hospitalization.
Abrupt withdrawal of treatment with an ACE inhibitor can lead to clinical deterioration and should be avoided43 in the absence of life-threatening complications (e.g., angioedema).
Every effort should be made to minimize the occurrence of sodium retention or depletion during long-term treatment with an ACE inhibitor, because changes in salt and water balance, as previously mentioned, can exaggerate or attenuate the cardiovascular and renal effects of treatment44. Fluid retention can minimize the symptomatic benefits of ACE inhibition, whereas fluid loss increases the risk of hypotension and azotemia. The use of an ACE inhibitor can also minimize or eliminate the need for long-term potassium supplementation.
Nonsteroidal anti-inflammatory drugs can block the favorable effects and enhance the adverse effects of ACE inhibitors in patients with HF and should be avoided. Retrospective analyses of large-scale clinical trials have suggested that aspirin might interfere with the benefits of ACE inhibition in patients with HF by inhibiting kinin- mediated prostaglandin synthesis. In short-term hemodynamic studies, aspirin can attenuate the hemodynamic actions of ACE inhibitors in patients with HF45, an effect not seen with non-aspirin anti-platelet agents (e.g., clopidogrel)46. In several multicenter trials, concomitant use of aspirin was associated with a diminution of the effect of ACE inhibitors on survival and on cardiovascular morbidity47.
A recent comprehensive systematic overview of 22.060 patients from 6 long-term randomized trials of ACEIs re-evaluated the issue of the potential detrimental effect of combining aspirin with ACEI therapy. When all of these trials were considered together, the effects of ACEIs were significantly beneficial in patients with and without aspirin
43 Pflugfelder PW, Baird MG, Tonkon MJ, DiBianco R, Pitt B. Clinical consequences of angiotensin- converting enzyme inhibitor withdrawal in chronic heart failure: a double-blind, placebo-controlled study of quinapril. The Quinapril Heart Failure Trial Investigators. J Am Coll Cardiol 1993;22:1557-63.
44 Cody RJ, Covit AB, Schaer GL, Laragh JH, Sealey JE, Feldschuh J. Sodium and water balance in chronic congestive heart failure. J Clin Invest 1986;77:1441-52.
45 Hall D, Zeitler H, Rudolph W. Counteraction of the vasodilator effects of enalapril by aspirin in severe heart failure. J Am Coll Cardiol 1992;20:1549-55.
46 Spaulding C, Charbonnier B, Cohen-Solal A, et al. Acute hemodynamic interaction of aspirin and ticlopidine with enalapril: results of a double-blind, randomized comparative trial. Circulation 998;98:757- 65.
47 Al Khadra AS, Salem DN, Rand WM, Udelson JE, Smith JJ,Konstam MA. Antiplatelet agents and survival: a cohort analysis from the Studies of Left Ventricular Dysfunction (SOLVD) trial. J Am Coll Cardiol 1998;31:419-25.