- Jennifer Middleton, MD, MPH
Angiotensin-converting enzyme inhibitors (ACEis) have been a first-line medication for hypertension for decades, with well-established mortality and morbidity benefits. Although newer on the block, angiotensin II receptor blockers (ARBs) have demonstrated many of these same benefits for patients and were included in the Eight Joint National Committee (JNC 8) guideline as another reasonable first-line option for treating hypertension. Initially cost-prohibitive for many patients, most ARBs are now available generic and at similar cost to ACEis, and data has been emerging that their tolerability profile is better than ACEis without sacrificing those all-important patient-oriented outcomes that matter (POEM) benefits. A large cohort study now adds to this evidence base, potentially furthering the case for choosing ARBs over ACEis for patients with hypertension.
The study authors reviewed 8 databases from across the United States, South Korea, and Germany that included over 3 million patients. They identified patients who were started on either an ACEi or an ARB for primary hypertension and noted outcomes related to both cardiovascular disease (CVD) events and adverse medication reactions. They used propensity score models to "adjust for potential confounding and improve balance between the ACE inhibitor and ARB patient cohorts...which included "tens of thousands of measured baseline covariates including: demographics, diagnoses,... [and] comorbidity or risk scores." There was no statistically significant difference between the ACEi and the ARB groups regarding risk of CVD events, but ACEi patients had more adverse medication reactions:
We found 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]). Across secondary and safety outcomes, patients on ARBs had significantly lower risk of angioedema, cough, pancreatitis, and GI bleeding.
Specifically, patients receiving ACEis were more likely to experience acute pancreatitis (hazard ratio [HR] 1.32 [95% CI 1.04-1.70]), angioedema (HR 3.31 [95% CI 2.55-4.51]), cough (HR 1.32 [95% CI 1.11-1.59]), and GI bleed (HR 1.18 [95% CI 1.01-1.41]).
It's important to note that this study was not a randomized controlled trial (RCT); patients were not prospectively divided into randomized groups to rigorously assess for differences between treatments. Its impossible to completely adjust for potential confounders, no matter how rigorous the propensity score models are. Then again, an RCT on this scale would be a sizable undertaking, and cohort study data can still provide useful information. This study is consistent with the findings of an earlier meta-analysis of head-to-head, ACEi versus ARB, RCTs that found no difference in CVD outcomes but increased patient drop-out in the ACEi group, presumably due to side effects.
This study also would not apply to patients already receiving appropriate treatment for hypertension that is effective and well-tolerated; that is, switching patients to an ARB from an ACEi who are already doing well isn't necessarily warranted. For those patients with a new hypertension diagnosis, though, and/or those patients whose blood pressure control is inadequate and need an additional agent, it may make sense to consider ARBs over ACEis. If you'd like to read more, there's an AFP By Topic on Hypertension which includes sections on Treatment, Improving Practice, and also resources from FPM.