ACEs & ARBs Similar in Event Prevention, But ARBs Have Favorable Safety Profile

RuiJen Chui, MD

Leveraging information from 8 databases across the US, Germany, and South Korea, researchers from Columbia University Irving Medical Center are providing clinicians with insight into the head-to-head effectiveness and safety of ACE (angiotensin-converting enzyme) inhibitors and angiotensin receptor blockers (ARBs).

Assessing more than 50 outcomes among a multinational cohort of more than 2.9 million patients with hypertension, investigators found both classes exhibited similar efficacy in reducing cardiovascular events but use of ARBs was associated with fewer adverse events, including tissue swelling, pancreas inflammation, cough, and others.

"In professional guidelines, several classes of medications are equally recommended as first-line therapies. With so many medicines to choose from, we felt we could help provide some clarity and guidance to patients and health care professionals," said lead investigator RuiJun Chen, MD, Assistant Professor at Geisinger Medical Center in Pennsylvania and Postdoctoral Fellow at Columbia University at the time of the study, in a press release from the American Heart Association.

With both classes recommended as first-line treatment for hypertension but an apparent lack of head-to-head studies comparing them, Chen and colleagues sought to assess the efficacy and safety of ACE inhibitors versus ARBs using real-world data. With this in mind, investigators designed their study as a retrospective, new-user comparative cohort analysis using data from 8 databases collecting information from 1996-2018 within the US, Germany and South Korea.

The specific databases used in the study were the IBM MarketScan Commercial Claims and Encounters database, IBM MarketScan Medicare Supplemental Beneficiaries database, IBM MarketScan Multi-state Medicaid database, Optum De-Identified Clinformatics Data Mart Database, Korea National Health Insurance Service/National Sample Cohort, IMS/ IQVIA Disease Analyzer Germany, Columbia University Irving Medical Center database, and the Optum De-Identified Electronic Health Record Dataset.

For inclusion in the investigators’ analyses, patients were required to have at least 1 year of prior observation in the database before treatment initiation, have a recorded diagnosis of hypertension at the time of initiating therapy or during the year prior, not have been previously exposed to any antihypertensive medication, and not initiate another antihypertensive therapy within 7 days of index exposure to an ACE inhibitor or ARB.

Investigators assessed for 55 total outcomes, including 4 primary efficacy outcomes and 51 secondary outcomes. The primary outcomes of interest were acute myocardial infarction (AMI), hospitalization for heart failure, ischemic or hemorrhagic stroke, and a composite of the aforementioned cardiovascular events. Secondary outcomes were mostly safety-based and were based on known or suspected side effects of antihypertensive medications.

From the databases, investigators identified 2,297,881 patients initiating therapy with an ACE inhibitor and 673,938 initiating treatment with an ARB. Overall, 39% of the patients were female, 175 had diabetes, 37% had hyperlipidemia, and 9% had a history of cardiovascular disease. The most commonly used ACE inhibitor was lisinopril (80%) and the most commonly used ARB was losartan (45%).

In adjusted analyses, investigators observed no statistically significant difference in AMI (HR, 1.11; 95% CI, 0.95-1.32), heart failure (HR, 1.03l 95% CI, 0.87-1.24), stroke (HR, 1.07; 95% CI, 0.91-1.27), or the composite cardiovascular outcome (HR, 1.06; 95% CI, 0.90-1.25) for patients using ACE inhibitors compared to ARBs. For safety outcomes, investigators pointed out significantly lower risks for 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), abnormal weight loss (HR, 1.18; 95% CI, 1.01-1.41; P=.04), and gastrointestinal bleeding (HR, 1.18; 95% CI, 1.01-1.41; P=.04).

"ARBs do not differ in effectiveness and may have fewer side effects than ACE inhibitors among those just beginning treatment," said Chen. "We unfortunately cannot extend these conclusions to people who are already taking ACE inhibitors or those who are taking multiple medications. We would reiterate that if you experience any side effects from your medicine, you should discuss with your doctor whether your antihypertensive regimen may need to be adjusted."

This study, “Comparative First-Line Effectiveness and Safety of ACE (Angiotensin-Converting Enzyme) Inhibitors and Angiotensin Receptor Blockers,” was published in Hypertension.