Dispelling the Myths about ACE Inhibitors and ARB Agents
Though used primarily in heart failure and hypertension, Angiotensin Converting Enzyme Inhibitors (ACEIs) and Angiotensin Receptor Blockers (ARBs) demonstrate nephroprotection by reducing glomerular capillary pressure and proteinuria, and slowing the decline of renal function. Nephroprotection should be employed in patients with chronic kidney disease or diabetic nephropathy, or those at risk. Although these effects are proven, doses in some clinical trials were generally 2-3 times higher than those used in clinical practice. It may be helpful to review some myths about these sometimes undervalued medications to ensure that prescriptions are being written for patients who may benefit from them the most.
MYTH #1: Rises in serum creatinine or potassium are unpredictable and warrant discontinuation.
Hyperkalemia and rises in creatinine are not absolute contraindications to ACEI or ARB therapy, and in most cases are predictable. ACEIs and ARBs reduce aldosterone, thus increasing potassium, and may increase creatinine by additive renal hypoperfusion. Limiting dietary potassium to <2-3g/day, discontinuing contributing medications (e.g. potassium-sparing diuretics, NSAIDs), or initiating a thiazide or loop diuretic may prevent hyperkalemia, while treating patients for heart failure or volume depletion prior to initiation of therapy may prevent detrimental rises in creatinine. Patients should not be discontinued unless potassium exceeds 5.6mmol/L, or resulting GFR declines reach more than 50%.
MYTH #2: ACEIs and ARBs should only be used in hypertensive patients.
The long-term reduction of renal disease progression by ACEIs and ARBs in diabetes goes above and beyond any effects attributable to blood pressure reduction. It is likely that hypertension is a result, not a cause of diabetic nephropathy, and risk for cardiovascular disease may be decreased. According to NKF guidelines, normotensive diabetics with macroalbuminuria are recommended for ACEI or ARB therapy, while patients with microalbuminuria should be considered for treatment and clinical judgment should be used for patients with normoalbuminuria. Starting with low doses and titrating to maximum dose without hypotension may be clinically valuable.
MYTH #3: Cough is an absolute contraindication to ACEI therapy.
Up to 20% of patients receiving an ACEI may develop a dry cough. This is due to elevation of bradykinin levels caused by ACEIs. If there is reasonable certainty that a patient's cough is due to ACEI therapy they should be switched to an ARB, which does not affect bradykinin levels. Angioedema, a contraindication to ACEI therapy, occurs in <1% of patients. Theoretically, angioedema should occur less frequently with ARBs but the safety of ARBs in patients with ACEI-associated angioedema has not been evaluated so ARBs should be used with caution in this situation.
MYTH #4: ACEIs and ARBs should never be used together.
Four major trials have been published using combination therapy. The VALIANT and ONTARGET studies concluded that despite blood pressure reductions, cardiovascular risk reductions were not achieved, and adverse effects were increased with combination therapy. The Valsartan Heart Failure Trial and CHARM-added study both looked at the effect of combination therapy in heart failure patients. While both showed a reduced risk for hospital admissions, the CHARM-added study also showed decreased mortality from cardiovascular causes and determined that combination therapy is beneficial in heart failure patients. If used together, patients should be monitored for adverse effects.
There is evidence that inhibition of the Renin Angiotensin Aldosterone System improves the outcomes of patients with diabetes, CKD, and cardiovascular disease. Treatment with ACEIs and ARBs has been shown to decrease costs, prevent chronic disease progression, and improve quality of care. Patients with diabetes and kidney disease need to be treated aggressively with ACEIs and ARBs. This is especially true if hypertension is also part of the picture. For additional information and references click here.
