An ACE in the Hole No More

Volume 6, Issue 2

ACE inhibitors have been a cornerstone therapy for managing hypertension for three decades. These medications are inexpensive, readily available, well tolerated, and effective in lowering blood pressure in nearly all groups of individuals. As such, they are currently recommended as first-line agents by every major guideline for hypertension. The angiotensin receptor blockers (ARBs) have historically been relegated to patients who were intolerant of ACE inhibitors due to cough or angioedema. However, now that these agents are no longer hindered by higher branded copayments, this practice of reserving ARBs behind ACE inhibitors needs to be revisited.

In this week’s issue of Talking Therapeutics, we explore a recent paper,¹ published in the journal Hypertension, which addresses this salient topic.

Point 1: ACE Inhibitors and ARBs Are Equally Effective

This new paper was a retrospective study comparing the drug classes among new-user cohorts of all patients with hypertension initiating monotherapy with an ACE inhibitor or ARB between 1996 and 2018 across eight databases from the US, Germany, and South Korea. The primary outcomes were acute myocardial infarction, heart failure, stroke, and composite cardiovascular events.

The study included 2,297,881 patients initiating treatment with ACE inhibitors and 673,938 patients starting ARBs. There were no statistically significant differences in the primary outcomes of acute myocardial infarction (hazard ratio [HR], 1.11; 95% CI, 0.95 to 1.32), heart failure (HR, 1.03; 95% CI, 0.87 to 1.24), stroke (HR, 1.07; 95% CI, 0.91 to 1.27), or composite cardiovascular events (HR, 1.06; 95% CI, 0.90 to 1.25).

Point 2: ARBs Appear to Be Safer Than ACE Inhibitors

In this same paper, patients on ACE inhibitors had significantly higher risk of angioedema (HR, 3.53; 95% CI, 2.99 to 4.16), cough (HR, 1.32; 95% CI, 1.23 to 1.42), pancreatitis (HR, 1.32; 95% CI, 1.09 to 1.60), and gastrointestinal bleeding (HR, 1.18; 95% CI, 1.11 to 1.25). Notably, the issue of weight gain with ARBs compared to ACE inhibitors was not explored. Nonetheless, given the findings supporting superior safety and equal efficacy, this large, real-world analysis supports the idea that ARBs should be preferentially prescribed over ACE inhibitors for patients with essential hypertension.

While the current hypertension guidelines offer no such preferential language, I expect that to change in the next iteration.

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Reference

1. 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 [published online ahead of print, 2021 Jul 26]. Hypertension. 2021;HYPERTENSIONAHA12016667. doi:10.1161/HYPERTENSIONAHA.120.16667