ACE Inhibitors vs. ARBs

ACE Inhibitors vs. ARBs
McKenzie Pfeffer, PharmD, St. Cloud VA Health System

Background: Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) are widely used in the United States for the treatment of hypertension and are among first-line therapy options, along with calcium channel blockers and thiazide or thiazide-like diuretics. Both ACEs and ARBs work on the renin-angiotensin system (RAS) in the kidneys, however, they have different sites of action. ACE inhibitors inhibit the conversion of angiotensin I to angiotensin II, while ARBs block receptor binding of angiotensin II. Generally, both classes are considered to be interchangeable and yield similar efficacies. Over the years, ACE inhibitors have been more widely used than ARBs due to previously lower cost, as well as additional benefits seen with improving mortality in heart failure and post-myocardial infarction (MI) along with renal protection in patients with diabetes. Generally well-tolerated, patients taking ACE inhibitors or ARBs occasionally complain of a chronic, dry, non-productive cough. Hyperkalemia and an increase in serum creatinine may be seen while using these agents. This can be serious since hyperkalemia can cause cardiac issues, including arrhythmias, which can be life-threatening. Lab monitoring, especially upon initiation of one of these agents, is imperative for patient safety. Generally, there is no difference between selecting an ACE inhibitor or ARB for first-line use in hypertension, although a new analysis of a large trial suggests otherwise.

Evidence: A recent large analysis of a major trial, LEGEND-HTN, originally published in American Heart Association Hypertension, now claims that ARBs are preferred over ACE-inhibitors for first-line treatment of hypertension. LEGEND-HTN is the largest head-to-head comparison trial with almost 3 million patients with hypertension who were started on a first-line antihypertensive including: ACE inhibitors, ARBs, dihydropyridine or non-dihydropyridine calcium channel blockers, and thiazide or thiazide-like diuretics. Researchers aimed to identify differences between the drug classes including incidence of acute MI hospitalization for heart failure, stroke, or a composite of these cardiovascular outcomes plus sudden cardiac death. Secondary efficacy and safety outcomes also were examined. Prior to LEGEND-HTN, Cochrane published a large review between ACE inhibitors and ARBs for primary hypertension. Findings from this analysis suggest that while ARBs are slightly better tolerated than ACE inhibitors, there is a higher quality of data supporting the use of ACE inhibitors to prevent strokes, heart disease, and death, which makes ACE inhibitors, as a class, more preferable over ARBs. Findings from the new analysis show that ARBs may move up and surpass ACE inhibitors for first-line hypertension treatment due to similar efficacy with better tolerability. Furthermore, there was no statistical difference in the primary cardiac outcomes between the two groups. However, patients receiving ARBs had lower incidence of angioedema, cough, acute pancreatitis, and gastrointestinal bleeding compared to those receiving ACE inhibitors. Lisinopril made up over 80% of the ACE inhibitor group, which may have carried disproportionate weight in the drug-class comparison. This study was designed around patients who were receiving antihypertensive medications for the first time. The results do not factor in patients who already take one of the drugs and are considering switching or adding another medication to their regimen.

Clinical Impact and Discussion: Both ACE inhibitors and ARBs are effective blood-pressure lowering medications that have been on the market for years. If clinically indicated, either agent would likely be effective in patients with hypertension. Cost differences between the two drug classes are minimal since both have generic products that are readily available. New data suggests that ARBs are just as efficacious as ACE inhibitors with fewer adverse effects associated with their use, including reduction in angioedema, cough, and potentially a decreased risk of pancreatitis and gastrointestinal bleeding, although more research is needed to validate these claims. When faced with a clinical decision to start a patient on an ACE or ARB, opting for an ARB may be a slam dunk by providing good blood pressure lowering, improving cardiovascular outcomes, and fewer adverse events compared with commonly prescribed ACE inhibitors.

References:

  1. Abbasi J. Choose ARBs over ACE inhibitors for first-line hypertension treatment, large new analysis suggests. JAMA. 2021;326(13): 1244-1245. doi:10.1001/jama.2021.14017
  2. Chen R, Suchard MA, Krumholz HM, et al. Comparative First-Line Effectiveness and Safety of ACE (Angiotensin-Converting Enzyme) Inhibitors and Angiotensin Receptor Blockers: A Multinational Cohort Study. Hypertension AHA. 2021;78:591-603. doi:10.1161/hypertensionaha.1201667
  3. Li ECK, Heran BS, Wright JM. Angiotensin converting enzyme (ACE) inhibitors versus angiotensin receptor blockers for primary hypertension (Review). Cochrane Database of Systematic Reviews. 2014;(8)1-44. doi:10.1002/14651858.