ARBs Equal ACE Inhibitors for Hypertension, but Better Tolerated

Nancy A. Melville

July 26, 2021

Dr George Hripcsak

In the largest comparison of angiotensin receptor blockers (ARBs) and angiotensin-converting enzyme (ACE) inhibitors to date, a study of nearly 2.3 million patients starting the drugs as monotherapy shows no significant differences between the two in the long-term prevention of hypertension-related cardiovascular events.

However, side effects were notably lower with ARBs.

"This is a very large, well-executed observational study that confirms that ARBs appear to have fewer side effects than ACE inhibitors, and no unexpected ARB side effects were detected," senior author George Hripcsak, MD, professor and chair of biomedical informatics at Columbia University Vagelos College of Physicians and Surgeons, New York City, told Medscape Medical News.

"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 (RAS) inhibition," the authors add in the study, published online July 26 in the journal Hypertension.

They note that both drug classes have been on the market a long time, with proven efficacy in hypertension and "a wide availability of inexpensive generic forms."

They also stress that their findings only apply to patients with hypertension for whom a RAS inhibitor would be the best choice of therapy.

Commenting on the research, George Bakris, MD, of the American Heart Association's Comprehensive Hypertension Center at the University of Chicago Medicine, Illinois, said the findings were consistent with his experience in prescribing as well as researching the two drug classes.

"I have been in practice for over 30 years and studied both classes, including head-to-head prospective trials to assess blood pressure, and found in many cases better blood pressure lowering by some ARBs and always better tolerability," he told Medscape Medical News.

"I think this study confirms and extends my thoughts between the two classes of blood pressure–lowering agents."

Head-to-Head Comparisons of ACE Inhibitors and ARBs Limited to Date

ACE inhibitors and ARBs each have extensive evidence supporting their roles as first-line medications in the treatment of hypertension, and each have the strongest recommendations in international guidelines.

However, ACE inhibitors are prescribed more commonly than ARBs as the first-line drug for lowering blood pressure, and head-to-head comparisons of the two are limited, with conflicting results.

For the study, Hripcsak and colleagues evaluated data on almost 3 million patients starting monotherapy with an ACE inhibitor or ARB for the first time between 1996 and 2018 in the United States, Germany, and South Korea, who had no history of heart disease or stroke.

They identified a total of 2,297,881 patients initiating ACE inhibitors and 673,938 starting ARBs.

Among new users of ACE inhibitors, most received lisinopril (80%), followed by ramipril and enalapril, while most patients prescribed ARBs received losartan (45%), followed by valsartan and olmesartan.

With follow-up times ranging from about 4 months to more than 18 months, the data show no statistically significant differences between ACE inhibitors versus ARBs in the primary outcomes of acute myocardial infarction (hazard ratio [HR], 1.11), heart failure (HR, 1.03), stroke (HR, 1.07), or composite cardiovascular events (HR, 1.06).

For secondary and safety outcomes, including an analysis of 51 possible side effects, ACE inhibitors compared with ARBs were associated with a significantly higher risk of angioedema (HR, 3.31; P < .01), cough (HR, 1.32; P < .01), acute pancreatitis (HR, 1.32; P = .02), gastrointestinal bleeding (HR, 1.18; P = .04), and abnormal weight loss (HR, 1.18; P = .04).

While the link between ACE inhibitors and pancreatitis has been previously reported, the association with GI bleeding may be a novel finding, with no prior studies comparing those effects in the two drug classes, the authors note.

Despite most patients taking just a couple of drugs in either class, Hripcsak said, "We don't expect that other drugs from those classes will have fewer differences. It is possible, of course, but that is not our expectation."

Results Only Applicable to Those Starting Therapy With RAS Inhibitors

First author RuiJun Chen, MD, added that, importantly, the results may not apply to patients switching therapies or adding on therapy, "such as for the patient whose hypertension is not effectively controlled with one drug and requires the addition of a second medication," he told Medscape Medical News.

"Also, the suggestion of preferentially prescribing ARBs only applies to those patients and providers intending to control blood pressure through RAS inhibition," said Chen, an assistant professor in translational data science and informatics at Geisinger Medical Center in Danville, Pennsylvania, who was a National Library of Medicine postdoctoral fellow at Columbia University at the time of the study.

Hence, he stressed the results do not extend to other classes of recommended first-line blood pressure medications.

"Essentially, since this is an ACE inhibitor versus ARB study, we would not claim that ARBs are preferred over all other types of hypertension medications which were not studied here," the researchers emphasize.

In addition to ARBs and ACE inhibitors, other medications recommended by the American Heart Association/American College of Cardiology in the 2017 Guideline for the Prevention, Detection, Evaluation and Management of High Blood Pressure in Adults for the primary treatment of hypertension include thiazide diuretics and calcium channel blockers.

The study received support from the National Library of Medicine and the National Institute of Allergy and Infectious Diseases of the National Institutes of Health; the National Science Foundation; and the Ministries of Health & Welfare and of Trade, Industry & Energy of the Republic of Korea. Hripcsak has reported receiving grants from the National Library of Medicine during the study and grants from Janssen Research outside the submitted work. Bakris has reported being a consultant for Merck, KBP Biosciences, and Ionis.

Hypertension. Published online July 26, 2021. Abstract

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