Similar effectiveness of ACEi and ARB as hypertension treatment in real-world
Comparative First-Line Effectiveness and Safety of ACE (Angiotensin-Converting Enzyme) Inhibitors and Angiotensin Receptor Blockers.
Introduction and methods
Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) are equally recommended as first-line therapy for the treatment of hypertension in the 2017 ACC/AHA and 2018 ESC/ESH guidelines. However, there are limited head-to-head studies comparing the effectiveness and safety of ACEi with ARBs as hypertension monotherapy and the few available studies have shown conflicting results [1-3]. Though, ACEi are far more commonly prescribed worldwide for the treatment of hypertension [4-7].
This long-term observational study compared the effectiveness and safety of ACEi or ARB therapy for first-line treatment of patients with hypertension in a real-world setting.
This study used 7 observational databases in the open-science LEGEND-HTN (Large-scale Evidence Generation and Evaluation across a Network of Database for Hypertension). All patients initiating antihypertensive treatment with a single drug (ACEi [n= n=2,297,881] or ARB [n=673,938]) were included. Data from July 1996 to March 2018 were used. Propensity score models were used to adjust for potential confounding and to improve balance between the ACEi and ARB patients cohorts. Also, calibration was applied to account for residual bias using negative control outcomes. The primary effectiveness outcomes were acute MI, HF hospitalization, stroke, and a composite CV events (CVEs) outcome consisting of MI, HF hospitalization, stroke, and sudden cardiac death. Secondary safety outcomes included angioedema, cough, hypotension, syncope, and electrolyte abnormalities.
- 48% of patients initiated monotherapy with an ACEi, while 15% of patients initiated treatment with an ARB.
- There were no differences between patients on ACEi vs. ARBs for the primary effectiveness outcome of acute MI (HR 1.11, 95% CI: 0.95-1.32), HF hospitalization (HR 1.03, 95% CI: 0.87-1.24), stroke (HR 1.07, 95% CI: 0.91-1.27) or CVEs (HR 1.06, 95% CI:0.90-1.25).
- Patients receiving ACEi had a significant elevated risk for acute pancreatitis (HR 1.32, 95% CI: 1.04-1.70, P=0.02), angioedema (HR 3.31, 95% CI: 2.55-4.51, P<0.01), cough (HR 1.32, 95% CI: 1.11-1.59, P<0.01), gastrointestinal bleed (HR 1.18, 95% CI: 1.01-1.41, P=0.04), and abnormal weight loss (HR 1.18, 95% CI: 1.01-1.41, P=0.04) as well as decreased risk of abnormal weight gain (HR 0.84, 95% CI: 0.74-0.98, P=0.04) compared to those treated with an ARB. Using a conservative Bonferronni correction, cough and angioedema remained significant.
This large observational study including over 3 million patients worldwide showed that the effectiveness of ACEi vs. ARB treatment as first-line therapy for the treatment of hypertension on CV outcomes was comparable. Cough and angioedema were increased in patients receiving ACEi compared to patients initiating ARB.