ARBs vs ACEis for hypertension: Is one better than the other?

There are no significant differences between ARBs* and ACE** inhibitors in long-term prevention of cardiovascular (CV) outcomes among people initiating the antihypertensive drugs as monotherapy, but the former comes with fewer side effects than the latter, reveals a large, head-to-head, real-world comparative study.  

“While current US and European guidelines consider ACE inhibitors and ARBs to be equally recommended first-line therapies ... These findings support preferentially prescribing ARBs over ACE inhibitors when initiating treatment for hypertension,” said the researchers.

Both ARBs and ACE inhibitors work by inhibiting the renin-angiotensin system (RAS) and have equal standing in guidelines as first-line therapies for the treatment of hypertension.

“ACE inhibitors and ARBs both carry the strongest recommendation, class I, as first-line agents for initiation of antihypertensive therapy,” the researchers stated.

“[Yet,] ACE inhibitors are far more commonly prescribed than ARBs … [even though] few head-to-head studies comparing ACE inhibitors with ARBs for hypertension treatment exist, some of which reach conflicting results,” they noted.

In the retrospective, comparative cohort study, the researchers compared hypertensive patients who initiated monotherapy with ACE inhibitors (n=2,297,881) or ARBs (n=673,938), identified from eight databases across the US, Germany, and South Korea. [Hypertension 2021;doi:10.1161/HYPERTENSIONAHA.120.16667]

During a follow-up duration ranging from 4 to >18 months, there were no statistically significant differences between ACE inhibitors vs ARBs for the primary outcomes of stroke (hazard ratio [HR], 1.07), acute myocardial infarction (HR, 1.11), heart failure (HR, 1.03), or composite CV events (HR, 1.06).

However, patients treated with ACE inhibitors had significantly higher risk of secondary and safety outcomes, including cough (HR, 1.32; p<0.01), angioedema (HR, 3.31; p<0.01), acute pancreatitis (HR, 1.32; p=0.02), and gastrointestinal (GI) bleeding (HR, 1.18; p=0.04).

While the association between ACE inhibitors and pancreatitis is known in previous reports, the connection with GI bleeding appears to be novel, according to the authors.

“Our large-scale, observational network study demonstrates that … 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,” they summed up.

Noting that ACE inhibitors and ARBs are grouped together as a single treatment category in international guidelines and are considered to be equally recommended, the researchers pointed out that “these results lend further support to recent calls for the differentiation and elevation of ARBs as first-line therapy over ACE inhibitors in the treatment of hypertension.”

Nonetheless, these findings apply only to patients and physicians who intend to control hypertension through RAS inhibition and for patients in whom a RAS inhibitor is considered the best choice, they explained.

“Our study was a comparison of first-line treatment only and may not be applicable to patients who are not initiating treatment such as those switching medications,” the researchers advised.

“Our study was also limited to the drug class level and as such, our findings may not extend to all individual drug level comparisons within these classes,” they added, while also cautioning against extrapolating the finding to ARBs as being preferred over all other classes of antihypertensives.

*ARBs: angiotensin receptor blockers

**ACE: angiotensin-converting enzyme