Two of the most common drugs used to treat high blood pressure, or hypertension, are angiotensin receptor blockers (ARBs) and angiotensin-converting enzyme inhibitors (ACEs). Some of the better-known ARBs are losartan (brand name Cozaar), valsartan (Diovan), olmesartan (Benicar), candesartan (Atacand), and irbesartan (Avapro), while popular ACE inhibitors include lisinopril (Qbrelis, Prinivil, Zestril), enalapril (Vasotec), moexipril (Univasc), benazepril hydrochloride (Lotensin), and ramipril (Altace). The mechanisms by which they work are different, but both affect a protein in the blood called angiotensin that narrows blood vessels, causing the heart to work harder and blood pressure to rise. Both classes of medications have been around for years and have proven to be safe and effective.
Although ACE inhibitors are more frequently prescribed than ARBs, there have been few studies comparing them. However, a newly released report comparing the two medications involved nearly three million people. According to lead author RuiJun Chen, MD, “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.”
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For the study, which was reported in Hypertension, a journal of the American Heart Association, the researchers collected data between 1996 and 2018 from eight electronic health record and insurance claim databases in the United States, Germany, and South Korea. The patients had no history of heart disease or stroke and were beginning monotherapy (the use of a single drug) with either an ACE inhibitor or an ARB. Nearly 2.3 million subjects were starting on ACE inhibitors, while some 674,000 were beginning ARBs. Lisinopril was by far the most-used ACE inhibitor, being taken by eight out of ten ACE inhibitor users, followed by ramipril and enalapril. About half of the ARB users took losartan, followed by valsartan and olmesartan. Follow-up times ranged from four months to more than a year and a half.
ARBs linked to fewer side effects
The researchers reported no significant differences between ARBs and ACE inhibitors when it came to preventing cardiovascular events related to high blood pressure — heart attacks (acute myocardial infarction), heart failure, stroke, or a combination of cardiovascular events. But they nevertheless did find a dissimilarity between the two treatments — side effects. Here the ARBs proved to have a superior track record. The researchers explored fifty-one possible side effects and reported that, compared with ARBs, ACE inhibitors showed a significantly higher risk of four. For one, the patients using ACE inhibitors were about three times more likely to develop angioedema (fluid accumulation and swelling of the deeper layers of the skin). The ACE inhibitor users were also 32% more likely to develop a cough, 32% more likely to develop pancreatitis, and 18% more likely to develop gastrointestinal (GI) bleeding. Previous research had noted a connection between ACE inhibitors and pancreatitis, but this appears to be the first study reporting a link to GI bleeding.
Given the association between ACE inhibitors and side effects, the authors wrote, “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…” One study author, George Hripcsak, MD, said, “This is a very large, well-executed observational study that confirms that ARBs appear to have fewer side effects than ACE inhibitors…”
Other medications besides ARBs and ACE inhibitors, such as thiazide diuretics and calcium channel blockers, are used to treat high blood pressure, and the results of this new study did not present information on them, the authors pointed out. According to Dr. Chen, “Essentially, since this 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.” He also noted that the findings might not apply to patients who need a second medication when a single one doesn’t control their blood pressure. In a press release, Dr. Chen said, “ARBs do not differ in effectiveness and may have fewer side effects than ACE inhibitors among those just beginning treatment. 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.”