 This study used a retrospective, new-user comparative cohort design to

estimate HRs.
 Large-scale propensity score adjustment, empirical calibration, and full
transparency minimized residual confounding and bias.
 The study cohort included all patients with hypertension starting ACEI
(n=2,297,881) or ARB (n=673,938) monotherapy between 1996 and 2018
across eight databases from US, Germany, and South Korea.
 Primary outcomes over follow-up times ranging from ~4 to >18 months
were acute myocardial infarction, heart failure, stroke, and composite
cardiovascular events.
 Angioedema, cough, syncope, and electrolyte abnormalities were
among 51 secondary and safety outcomes studied.
 Among new ACEI users, 80% received lisinopril, with ramipril and
enalapril being next most commonly prescribed.
 Most patients prescribed ARBs received losartan (45%), followed by
valsartan and olmesartan.
 ACEIs versus ARBs did not differ statistically significantly in acute
myocardial infarction (HR, 1.11; 95% confidence interval [CI], 0.95-1.32),
heart failure (HR, 1.03; 95% CI, 0.87-1.24), stroke (HR, 1.07; 95% CI, 0.91-
1.27), or composite cardiovascular events (HR, 1.06; 95% CI, 0.90-1.25).
 However, patients receiving ACEIs had significantly higher risk for
angioedema (HR, 3.31; P<.01), cough (HR, 1.32; P<.01), acute pancreatitis
(HR, 1.32; P=.02), GI bleeding (HR, 1.18; P=.04), and abnormal weight loss
(HR, 1.18; P=.04) than those receiving ARBs.
 No unexpected adverse effects of ARBs were identified.
 The investigators concluded that in their large-scale, observational
network study, ARBs did not differ statistically significantly in real-world
effectiveness at the class level from ACEIs as first-line treatment for
hypertension, but they had a better safety profile.
 Both drug classes have a long history of availability, proven efficacy in
hypertension, and wide availability of inexpensive generic formulations.
 The association of ACEIs with pancreatitis was previously reported,
but the increased risk for GI bleeding may be a new finding, as no previous
studies compared that effect between the 2 drug classes.
 The findings support preferentially prescribing ARBs over ACEIs
when starting treatment for hypertension in patients in whom RAS inhibition
is appropriate, despite their equal standing in current guidelines.
 The findings apply only to patients for whom an RAS system inhibitor
would be the best choice of therapy for hypertension, and not to other classes
of recommended first-line blood pressure medications, which were not
studied.
 The findings may also not apply to patients changing or adding
antihypertensive agents when initial treatment did not achieve sufficient
control.
 For primary treatment of hypertension, American Heart
Association/American College of Cardiology 2017 Guideline for the
Prevention, Detection, Evaluation and Management of High Blood Pressure
in Adults recommends ARBs, ACEIs, thiazide diuretics, and calcium channel
blockers.
 Further research should address whether there are differences in safety
and efficacy among individual drugs in the ARB and ACEI classes.
 Study limitations include observational design with potential residual
confounding.
Clinical Implications
 ARBs were as effective as ACEIs as first-line treatment for
hypertension but had a better safety profile.
 The findings support preferentially prescribing ARBs over ACEIs
when starting treatment for hypertension.
 Implications for the Health Care Team: Members of the healthcare
team are a vital part of ensuring patients with hypertension are properly
treated. It is important to recognize that the findings of this study apply only
to patients for whom RAS system inhibition would be the best choice of
therapy, and not to other classes of recommended first-line BP medications.
Cl

1. You are a member of the health care team for a 57-year-old man
newly diagnosed with hypertension. On the basis of the retrospective,
multinational cohort study by Chen and colleagues, which one of the
following statements about the real-world effectiveness and safety of
 angiotensin-converting enzyme inhibitors (ACEIs) versus angiotensin
receptor blockers (ARBs) in first-line treatment of hypertension is correct?

Answer: ARBs had a better safety profile than ACEIs

ACEIs and ARBs did not differ statistically significantly in AMI (hazard ratio,
1.11; 95% confidence interval, 0.95-1.32), heart failure (1.03; 0.87-1.24),
stroke (1.07; 0.91-1.27), or composite cardiovascular events (1.06; 0.90-
1.25). However, patients receiving ACEIs had significantly higher risk for
angioedema (hazard ratio, 3.31; P<.01), cough (1.32; P<.01), acute
pancreatitis (1.32; P=.02), GI bleeding (1.18; P=.04), and abnormal weight
loss (1.18; P=.04) than those receiving ARBs. Among new ACEI users,
80% received lisinopril, with ramipril and enalapril being next most
commonly prescribed. Most patients prescribed ARBs received losartan
(45%), followed by valsartan and olmesartan. The authors concluded that
ARBs did not differ statistically significantly in real-world effectiveness at
the class level from ACEIs as first-line treatment for hypertension, but they
did have a better safety profile.

2. According to the retrospective, multinational cohort study by Chen

and colleagues, which one of the following statements about the clinical
implications of the real-world effectiveness and safety of ACEIs versus
ARBs in first-line treatment of hypertension is correct?

Answer: The findings support preferentially prescribing ARBs over ACEIs

when starting treatment for hypertension in patients in whom renin-
angiotensin system (RAS) inhibition is appropriate
The findings do not apply to classes of recommended first-line blood
pressure medications other than RAS system inhibitors, which were not
studied. The findings may also not apply to patients changing or adding
antihypertensives when initial therapy did not achieve sufficient control.
Both drug classes have a long history of availability and proven efficacy in
hypertension and wide availability of inexpensive generic formulations. The
findings support preferentially prescribing ARBs over ACEIs when starting
treatment for hypertension in patients in whom RAS inhibition is
appropriate, despite their equal standing in current guidelines. The
association of ACEIs with pancreatitis was previously reported, but
increased risk for GI bleeding may be a new finding, as no previous studies
compared it between ACEIs and ARBs. Future research should study
safety/efficacy differences among individual ARBs and ACEIs.