ACE Inhibitors vs ARBs for First-Line Hypertension Treatment

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Currently, ACE inhibitors and ARBs are both recommended as first-line therapies for the treatment of hypertension according to US and European guidelines.

Angiotensin receptor blockers (ARBs) were found to be equally effective to angiotensin-converting enzyme (ACE) inhibitors for first-line treatment of hypertension; however ARBS may be less likely to cause adverse effects, according to the findings of a multinational cohort study recently published in Hypertension.

Currently, ACE inhibitors and ARBs are both recommended as first-line therapies for the treatment of hypertension according to US and European guidelines. Because there are limited head-to-head comparisons analyzing ACE inhibitors and ARBs, this retrospective, cohort study utilized real-world data from 8 databases in the United States, Germany, and South Korea to compare the safety and efficacy of these 2 medication classes.

Patients included in the study were required to have initiated ACE inhibitor or ARB monotherapy between 1996 and 2018 for the treatment of hypertension. Hazard ratios were estimated using techniques to minimize both residual confounding as well as bias. The primary outcomes of the study included acute myocardial infarction (AMI), heart failure (HF), stroke, and composite cardiovascular events (CVEs). Additionally, 51 secondary and safety outcomes were analyzed, including angioedema, cough, syncope, and electrolyte abnormalities.

Analysis of the 8 databases yielded a total of 2,297,881 patients who initiated an ACE inhibitor and 673,938 who initiated an ARB. “We found no statistically significant differences between patients on ACE inhibitors and patients on ARBs for risk of the primary outcomes of AMI (HR, 1.11 [95% CI, 0.95-1.32]), HF (HR, 1.03 [95% CI, 0.87-1.24]), stroke (HR, 1.07 [95% CI, 0.91-1.27]), or composite CVEs (HR, 1.06 [95% CI, 0.90-1.25]),” the authors reported.

Analysis of the secondary and safety outcomes revealed ACE inhibitors to be associated with a significantly increased risk of angioedema (HR, 3.31; 95% CI, 2.55-4.51; P <.01), cough (HR, 1.32; 95% CI, 1.11-1.59; P <.01), acute pancreatitis (HR, 1.32; 95% CI, 1.04-1.70; P =.02), and gastrointestinal bleeding (HR, 1.18; 95% CI, 1.01-1.41; P =.04) compared with ARBs.

“Despite being equally guideline-recommended first-line therapies for hypertension, these results support preferentially starting ARBs rather than ACE inhibitors when initiating treatment for hypertension for physicians and patients considering renin-angiotensin system inhibition,” the authors concluded.

Study limitations included variations in follow-up time and medication choice. The most used ACE inhibitor was reported to be lisinopril (80%), while the most used ARB was losartan (45%). “While this study compared these 2 drug classes, further study may be warranted to investigate any potential heterogeneity that may exist at the individual drug level,” the authors added. It is also unclear whether the results are generalizable to individuals prescribed combination therapies.

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.


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. Published online July 26, 2021. doi: 10.1161/HYPERTENSIONAHA.120.16667