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A new study asks which of the two most common hypertension medications works best. TEK IMAGE/Getty Images

ACE inhibitors and ARBs are equally recommended as first-line medications in the treatment of high blood pressure.

Currently, doctors prescribe ACE inhibitors more often than they do ARBs. However, few studies have compared the two classes of drugs directly.

A recent study published in Hypertension, an American Heart Association journal, set out to do just that. Study authors investigated whether there were any differences between the two sets of medication in terms of effectiveness and side effects.

ACE inhibitors and ARBs act on the renin-angiotensin-aldosterone system, which is a system of hormones that help regulate blood pressure. While both ACE inhibitors and ARBs are effective, the way they reduce hypertension is different.

Angiotensin is a hormone that narrows blood vessels, thereby restricting blood flow and increasing blood pressure. ACE inhibitors block an enzyme that triggers the production of angiotensin, which therefore reduces blood pressure.

ARBs block angiotensin receptors in the blood vessels. This diminishes the blood vessel-constricting effects of the angiotensin.

While people who are beginning treatment for high blood pressure can benefit equally from either of these medications, the recent study reports that ARBs may have fewer medication-related side effects than the ACE inhibitors.

The large-scale study focused on over 3 million participants with no history of heart disease or stroke who began high blood pressure treatment using ACE inhibitors or ARBs.

Eight electronic health record and insurance claim databases in the United States, Germany, and South Korea provided data for the study.

While prior research points to the similar effectiveness of these medications, information was limited or missing with regard to head-to-head comparisons of medication side effects in those who are starting hypertension treatments.

In addition, disagreement exists between studies as to whether ACE inhibitors, due to their longer history of use, should be the preferred form of treatment.

“With so many medicines to choose from, we felt we could help provide some clarity and guidance to patients and healthcare professionals,” says author RuiJun Chen, assistant professor in translational data science and informatics at Geisinger Medical Center in Danville, PA.

Researchers compared the occurrence of heart-related events and stroke among nearly 2.5 million people treated with ACE inhibitors with almost 700,000 patients treated with ARBs.

They also considered 51 different medication side effects between the two groups.

While finding no significant differences in the occurrence of any cardiac event, the study authors noticed major differences in observed side effects.

Compared with those taking ARBs, people who took ACE inhibitors were around 30% more likely to develop a persistent dry cough.

Dr. Matthew Tomey, a cardiologist and assistant professor of medicine and cardiology at the Icahn School of Medicine at Mount Sinai in New York City, NY, told Medical News Today that the chronic cough associated with ACE inhibitors is often the reason a prescriber will switch a patient from an ACE inhibitor to an ARB.

Results from the study also show that people taking ACE inhibitors were three times more likely to develop fluid accumulation, swelling of the deeper layers of the skin and mucous membranes, and a sudden inflammation of the pancreas.

Finally, those taking ACE inhibitors were 18% more likely to develop gastrointestinal bleeding.

In an interview with MNT, Dr. Gosia Wamil, Ph.D., a cardiologist at Mayo Clinic Healthcare in London, United Kingdom, made the following point after reviewing the study,

“Given the likely potentially life threatening consequences of these adverse events, these are important warnings, which we will need to watch carefully when prescribing ACE [inhibitors].”

However, Dr. Wamil also made it clear that retrospective observational studies such as these are “limited by residual confounding and bias.” She explained that, when the authors conducted further analyses with corrections, they “did not fully reproduce the level of statistical significance.”

While this study is notably strong in the number of patients tracked, the authors note several limitations. Among these is the possibility that because all the participants were just beginning treatment for hypertension, the results may not be applicable to people who were being treated and switched medications.

Dr. Wamil commented on the need for more head-to-head analyses between these two drug types. She believes approaching the study from an economic perspective, such as evaluating and comparing generic forms of these medicines, would be especially valuable for the public.

Agreeing with the need for further study, Dr. Tomey said, “Observational studies, such as this one, are important tools to generate hypotheses, but they seldom provide final answers.” For that, he explained, we need randomized clinical trials.

Dr. Tomey mentioned patients who may have other preexisting medical conditions that need to be treated along with hypertension. He concluded: “We need to be sensitive to the fact that certain specific groups of patients may yet get superior benefits from one drug over the other.”

“Although the authors of this study suggest that their findings support preferential prescribing of ARB over ACE due to their better safety profile,” Dr. Wamil concluded, “I believe the main message from that study supports the use of these two groups of antihypertensive drugs in the prevention of major cardiovascular events.”