Expert consensus document on angiotensin-converting enzyme inhibitors in cardiovascular disease

Abstract

Study Question: What is the rationale and indications for ACE inhibitors (ACE-I)? Here are 10 items to take home from the ESC Consensus Document: 1. Evidence-based indications for ACE-I include the following: hypertension; CHF; asymptomatic LV systolic dysfunction to reduce future CHF and sudden death, in the early stage and following an acute myocardial infarction; atherosclerotic vascular disease; diabetes. 2. By reducing formation of angiotensin-II (ang-II), ACE-I promotes the following: arterial and venous dilation; lowering of the PVR and increasing venous capacitance; increase in renal blood flow, natriuresis, and decrease in sympathetic tone; increase in bradykinin, which stimulates release of nitric oxide (NO) and prostaglandins and vasodilation; decrease in aldosterone (acutely), renin, adrenalin, vasopressin, and ACTH; reduction of platelet adhesion and aggregation and PAI-I; reduction in markers of inflammation including IL-6, chemotactic proteins and adhesion molecules; and reduction in oxidation of lipids and formation of tissue superoxide anions and other pro-oxidants. 3. ACE-I induced afterload reduction and antiproliferative effects results in reduced ventricular remodeling after an MI and decrease in myocardial fibrosis: prevention and reduction of cardiac hypertrophy in hypertension; enhanced endothelial function in normotensive patients with CAD, diabetes, and CHF. 4. Pharmokinetic profiles of available ACE-I vary by half-life, degree of renal excretion, and lipophilicity and tissue penetration. Dose reduction is necessary when the creatinine clearance is <30 mL/min (except fosinopril and trandolapril). The clinical relevance of varying tissue concentration is not clear. 5. All available ACE-I can be considered equally effective for lowering blood pressure. The choice and dose of ACE-I for each indication should be based upon the results of clinical trials where the benefit has been demonstrated. 6. Low blood pressures (sBP <90 mm Hg) are acceptable during ACE-I treatment if the patient is asymptomatic and renal function is not significantly affected. A relatively low BP and mild elevation of potassium are not contraindications to ACE-I. 7. ACE-I results in a reduction in proteinuria and rate of progression of renal disease in diabetes. By inducing efferent arteriolar vasodilation and decreased glomerular filtration, ACE-I can increase the creatinine level. A rising creatinine should not be an indication for discontinuing the ACE-I unless it increase by >50% or >3 mg/dL. Acute renal failure is uncommon in the absence of dehydration and renal artery stenosis. 8. Hyperkalemia due to ACE-I is more frequent in renal impairment, CHF, the elderly, with potassium supplements or potassium-sparing diuretics, heparin, and NSAIDs. NSAIDs should be avoided in patients on ACE-I, particularly with CHF, low BP, and renal impairment. There is little evidence for a reduction in the benefit of ACE-I in the presence of ASA. ACE-I can also increase the levels of digoxin and lithium. 9. ACE-I cough occurs in 5–10% of patients and may be related to bradykinin or substance P. The cough is not dose related and does not vary among the ACE-I. Angioedema is a rare but life-threatening side effect. Manifestations vary from severe laryngeal edema and marked swelling of lips to mild GI disturbance including nausea, vomiting and diarrhea. 10. The dose of ACE-I varies with the clinical setting and individual clinical response. The starting dose should be low and progressively increased to the dose regimens shown to be effective in clinical trials, providing the dose is well tolerated. Though patients, payers, and providers express concern about polypharmacy, the benefits of ACE-I in cardiovascular disease should be considered as independent of and additive to the other prevention strategies. MR