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Caution is required in patients with very low systolic blood pressure (<80 mm Hg), markedly increased serum levels of creatinine (greater than 3 mg per dL), bilateral renal artery stenosis or elevated levels of serum potassium (greater than 5.5 mmol per L).

Finally, treatment with an ACE inhibitor should not be initiated in hypotensive patients who are at immediate risk of cardiogenic shock. Such patients should first receive appropriate treatment for their HF and then be re-evaluated for ACE inhibition once stability has been achieved.

Initiation and maintenance

Although most of the evidence supporting an effect of ACE inhibitors on the survival of patients with HF is derived from experience with enalapril, the available data suggest that there are no differences among available ACE inhibitors in their effects on symptoms or survival42.

Although some have suggested that drugs in this class may differ in their ability to inhibit tissue ACE, no trial has shown that tissue ACE-inhibiting agents are superior to other ACE inhibitors in any clinical aspect of HF. Nevertheless, in selecting among ACE inhibitors, it is recommended to give preference to ACE inhibitors that have been shown to reduce morbidity and mortality in clinical trials (captopril, enalapril, lisinopril, and ramipril), because these studies have clearly defined a dose that is effective in modifying the natural history of the disease.

Treatment with an ACE inhibitor should be initiated at very low doses, followed by gradual increments in dose if lower doses have been well tolerated. Renal function and serum potassium should be assessed within 1 to 2 weeks of initiation of therapy and periodically thereafter, especially in patients with pre-existing hypotension, hyponatremia, diabetes, or azotemia or in those taking potassium supplements.

Because fluid retention can blunt the therapeutic effects and fluid depletion can potentiate the adverse effects of ACEI, physicians should ensure that patients are being given appropriate doses of diuretics before and during treatment with these drugs.

Short- and long-term therapy with ACE inhibitors is usually well-tolerated by the large majority (85% to 90%) of patients with HF. Physicians should attempt to prescribe doses of an ACE inhibitor that have been shown to reduce the risk of cardiovascular events in clinical trials. If these target doses, which are high rather than medium, cannot be used or are poorly tolerated, lower doses should be used. Once the drug has been titrated to the appropriate dose, patients can generally be maintained on long-term therapy with an ACE inhibitor with little difficulty.

42 Garg R, Yusuf S. Overview of randomized trials of angiotensin-converting enzyme inhibitors on mortality and morbidity in patients with heart failure. Collaborative Group on ACE Inhibitor Trials. JAMA 1995;273:1450-6.

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