ACE inhibitors and ARBs: Managing potassium and renal function
Release date: September 1, 2019
Expiration date: August 31, 2020
Estimated time of completion: 1 hour
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ABSTRACT
Angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) are used primarily to treat hypertension and are also useful for conditions such as heart failure and chronic kidney disease, independent of their effect on blood pressure. This article reviews the indications for ACE inhibitors and ARBs and offers advice for managing their adverse effects, particularly declining renal function and hyperkalemia.
KEY POINTS
- ACE inhibitors and ARBs reduce proteinuria by lowering the intraglomerular pressure, reducing hyperfiltration.
- These drugs tend to raise the serum potassium level and reduce the glomerular filtration rate (GFR). Monitoring the serum potassium and creatinine levels and the GFR is therefore imperative.
- Despite the benefits, concern for adverse effects including hyperkalemia and a rise in serum creatinine has led to reluctance to prescribe these drugs, and they are underused in the patients who may derive the greatest benefit.
ACE INHIBITORS, ARBs, ABD RENAL FUNCTION
Another concern about using ACE inhibitors and ARBs, especially in patients with chronic kidney disease, is that the serum creatinine level tends to rise when starting these drugs,29 although several studies have shown that an acute rise in creatinine may demonstrate that the drug is actually protecting the kidney.30,31 Hirsch32 described this phenomenon as “prerenal success,” proposing that the decline in GFR is hemodynamic, secondary to a fall in intraglomerular pressure as a result of efferent vasodilation, and therefore should not be reversed.
Schmidt et al,33,34 in a study in 122,363 patients who began ACE inhibitor or ARB therapy, found that cardiorenal outcomes were worse, with higher rates of end-stage renal disease, myocardial infarction, heart failure, and death, in those in whom creatinine rose by 30% or more since starting treatment. This trend was also seen, to a lesser degree, in those with a smaller increase in creatinine, suggesting that even this group of patients should receive close monitoring.
Whether renin-angiotensin-aldosterone system inhibitors provide a benefit in advanced progressive chronic kidney disease remains unclear.35–37 The Angiotensin Converting Enzyme Inhibitor (ACEi)/Angiotensin Receptor Blocker (ARB) Withdrawal in Advanced Renal Disease trial (STOP-ACEi),38 currently under way, will provide valuable data to help close this gap in our knowledge. This open-label randomized controlled trial is testing the hypothesis that stopping ACE inhibitor or ARB treatment, or a combination of both, compared with continuing these treatments, will improve or stabilize renal function in patients with progressive stage 4 or 5 chronic kidney disease.
,NEED FOR MONITORING
Taken together, the above data suggest close and regular monitoring is required in patients receiving these drugs. However, monitoring tends to be lax.34,37,39 A 2017 study of adherence to the guidelines for monitoring serum creatinine and potassium after starting an ACE inhibitor or ARB and subsequent discontinuation found that fewer than 10% of patients had follow-up within the recommended 2 weeks after starting these drugs.34 Most patients with a creatinine rise of 30% or more or a potassium level higher than 6.0 mmol/L continued treatment. There was also no evidence of increased monitoring in those deemed at higher risk of these complications.
WHAT DO THE GUIDELINES SUGGEST?
ACE inhibitors and ARBs in chronic kidney disease and hypertension
Target blood pressures vary in guidelines from different organizations.4,40–45 The 2017 joint guidelines of the American College of Cardiology and American Heart Association (ACC/AHA)40 recommend a target blood pressure of 130/80 mm Hg or less in all patients irrespective of the level of proteinuria and whether they have diabetes mellitus, based on several studies.46–48 In the elderly, other factors such as the risk of hypotension and falls must be taken into consideration in establishing the most appropriate blood pressure target.
In general, a renin-angiotensin-aldosterone system inhibitor is recommended if the patient has diabetes, stage 1, 2, or 3 chronic kidney disease, or proteinuria. For example, the guidelines recommend a renin-angiotensin-aldosterone system inhibitor in diabetic patients with albuminuria.
None of the guidelines recommend routine use of combination therapy.
ACE inhibitors and ARBs in heart failure
The 2017 ACC/AHA and Heart Failure Society of America (HFSA) guidelines for heart failure49 recommend an ACE inhibitor or ARB for patients with stage C (symptomatic) heart failure with reduced ejection fraction, in view of the known cardiovascular morbidity and mortality benefits.
The European Society of Cardiology50 recommends ACE inhibitors for patients with symptomatic heart failure with reduced ejection fraction, as well as those with asymptomatic left ventricular systolic dysfunction. In patients with stable coronary artery disease, an ACE inhibitor should be considered even with normal left ventricular function.
ARBs should be used as alternatives in those unable to tolerate ACE inhibitors.
Combination therapy should be avoided due to the increased risk of renal impairment and hyperkalemia but may be considered in patients with heart failure and reduced ejection fraction in whom other treatments are unsuitable. These include patients on beta-blockers who cannot tolerate mineralocorticoid receptor antagonists such as spironolactone. Combination therapy should be done only under strict supervision.50
