New York—Two commonly prescribed blood pressure medication classes appear to work equally well but notably differ on side effect profiles, according to a new study.

The research, published in Hypertension, focused on angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) for patients initiating antihypertensives. The authors point out that, while ACE inhibitors might be prescribed more often in that situation, ARBs work as well with apparently fewer side effects.

That information came from an analysis of eight electronic health-record and insurance-claim databases in the United States, Germany, and South Korea. The study team looked at records for nearly 3 million patients taking a high blood pressure medication for the first time with no history of heart disease or stroke.

Background information in the articles notes that both ACE inhibitors and ARBs target the renin-angiotensin-aldosterone system. Blood pressure is reduced because ACE inhibitors block an enzyme early in the system, resulting in lower production of angiotensin, which can narrow blood vessels. ARBs, meanwhile, help blood vessels avoid constriction by blocking receptors to which angiotensin attaches.

“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 author RuiJun Chen, MD, MA, assistant professor in translational data science and informatics at Geisinger Medical Center in Danville, Pennsylvania, and a postdoctoral fellow at Columbia University at the time of the study.

The AHA/ACC 2017 Guideline for the Prevention, Detection, Evaluation and Management of High Blood Pressure in Adults lists the primary medications for treating high blood pressure as thiazide diuretics, ACE inhibitors, ARBs, and calcium channel blockers. Physical activity and other lifestyle changes are also recommended for managing all levels of high blood pressure, even if medication is suggested.

Pointing out, however, that little research has compared the two, the authors sought to determine the real-world effectiveness and safety of ACE inhibitors versus ARBs in the first-line treatment of hypertension.

The study included all patients with hypertension initiating monotherapy with an ACE inhibitor or ARB between 1996 and 2018 in the international databases. Defined as the primary outcomes were acute myocardial infarction, heart failure, stroke, and composite cardiovascular events. The research team also considered 51 secondary and safety outcomes, including angioedema, cough, syncope, and electrolyte abnormalities.

Among the nearly 2.3 million patients initiating treatment with ACE inhibitors and 674,000 patients with ARBs, the researchers said they identified no statistically significant difference in the primary outcomes of acute myocardial infarction (hazard ratio, 1.11 for ACE versus ARB [95% CI, 0.95-1.32]), heart failure (hazard ratio, 1.03 [0.87-1.24]), stroke (hazard ratio, 1.07 [0.91-1.27]), or composite cardiovascular events (hazard ratio, 1.06 [0.90-1.25]).

On the other hand, with secondary and safety outcomes, patients on ARBs had significantly lower risk of angioedema, cough, pancreatitis, and gastrointestinal bleeding. Specifically, compared with patients taking ARBs, those prescribed ACE inhibitors were:
• 3.3 times more likely to develop fluid accumulation and angioedema
• 32% more likely to develop a possibly dry, persistent cough
• 32% more likely to develop pancreatitis
• 18% more likely to develop bleeding in the gastrointestinal tract

“In our large-scale, observational network study, ARBs do not differ statistically significantly in effectiveness at the class level compared with ACE inhibitors as first-line treatment for hypertension but present a better safety profile,” the researchers conclude. “These findings support preferentially prescribing ARBs over ACE inhibitors when initiating treatment for hypertension.”

“We did not detect a difference in how the two types of medicine reduced the complications of hypertension, but we did see a difference in side effects,” further explained senior author George Hripcsak, MD, professor and chair of biomedical informatics at Columbia University Vagelos College of Physicians and Surgeons and medical informatics services director at New York-Presbyterian/Columbia University Irving Medical Center. “If a patient is starting hypertension therapy for the first time, our results point to starting with the ARB over the ACE inhibitor.”

Dr. Chen pointed out that the findings are limited to those initiating blood pressure medications, stating, “We unfortunately cannot extend these conclusions to people who are already taking ACE inhibitors or those who are taking multiple medications.”

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