ACE Inhibitor

Treatment with an ACE inhibitor decreases preload and afterload by blunting the exaggerated peripheral compensatory response. ACE inhibitors should be considered first-line therapy for HF owing to systolic dysfunction. Many clinical trials have provided consistent evidence that ACE inhibitors result in decreased symptoms, improved quality of life, 30% to 35% fewer hospitalizations, and 20% to 25% reductions in mortality for patients with NYHA class II-IV HF. In addition, ACE inhibitors slow the progression to HF among patients with asymptomatic LV systolic dysfunction. Although the positive effects of ACE inhibitors probably apply to all available drugs in this class, enalapril, captopril, lisinopril, and ramipril have the strongest evidence for mortality reductions. The physician should initiate treatment at low dosage and titrate to the doses shown to be effective in clinical trials. Improved patient outcomes appear to be dose related.

Contraindications to using an ACE inhibitor use include pregnancy, bilateral renal artery stenosis, angioedema or other allergic responses, or documented persistent intolerance to ACE inhibitor (symptomatic hypotension, severe renal dysfunction, hyperkalemia, or cough). To minimize the risk of symptomatic hypotension the lowest possible starting dose should be given to patients with hyponatremia (<135 meg/L), recent increase in diuretic dose, serum creatinine >1.7 mg/dL, and patients over 75 years of age. Physicians should consider giving a test dose of a short acting ACE inhibitor (captopril 6.25 mg) and observing the patient in the office for 2 hours before starting daily ACE inhibitor therapy in patients at risk for symptomatic hypotension.

Serum urea nitrogen, serum creatinine, and potassium concentrations, and blood pressure should be determined before starting ACE inhibitor therapy, within a few weeks after initiating therapy, and after changes in dose. If baseline serum creatinine

is 3.0 mg/dL or greater, ACE inhibitors should be used with caution or in consultation with a specialist and titrated upward slowly to a maximum of half the usual target dose. As many as 25% of patients may have some improvement in renal function with ACE inhibitors, but a larger proportion (30%-35%) will show an elevation of serum creatinine. The average increase in creatinine is 0.4 mg/dL with most of the change observed in the first 6 weeks. The reversible renal dysfunction caused by ACE inhibitors may resolve with a careful decrease in diuretic dose. If creatinine stabilizes at less than 3.0 mg/dL, and hyperkalemia or symptomatic hypotension are not persistent, ACE inhibitors should be continued and titrated up to target doses. Serum potassium should be monitored carefully during dose titration in patients who are also receiving a potassium-sparing diuretic due to the increased risk of hyperkalemia. Systolic blood pressure of 90 to 100 should not deter the physician from titrating to target doses unless hypotension becomes symptomatic. Nonproductive cough is a common adverse effect of ACE inhibitors secondary to increased bradykinin levels. Cough may not be attributable to ACE inhibitors in a given HF patient since it is a common HF symptom. Only 1% to 2.5% of patients in large clinical trials discontinued ACE inhibitors due to cough.For patients with cough on an initial ACE inhibitor trial, switching to an alternative ACE inhibitor may diminish cough symptoms.