Ramipril

To address concerns that RAAS blockers might increase ACE2 expression and thereby heighten risk of SARS‑CoV‑2 infection, diabetic db/db mice were treated with ramipril for 8 weeks. Kidney ACE2 activity was higher in db/db mice than in non‑diabetic controls, but ramipril had no additional effect. In the lung, no differences in ACE2 activity were found between diabetic and non‑diabetic mice, and ramipril did not change it. In the heart, diabetes reduced ACE2 activity, and ramipril slightly increased it. The authors conclude that ramipril does not significantly affect lung ACE2 activity in this model, making it unlikely that ACE inhibitors increase COVID‑19 risk through this mechanism.

Fig. 1 ACE2 localization in kidney and heart tissue of the db/m, db/db and db/db treated with ramipril mice. (Vergara A, et al., 2021)

In a PROBE trial (186 patients, median age 83 years, LVEF >40%), ramipril versus standard care after successful transcatheter aortic valve implantation was compared. The primary composite endpoint (cardiac mortality, heart failure readmission, stroke at 1 year) occurred in 10.6% with ramipril and 12% with control (P=0.776). However, heart failure readmissions were significantly lower with ramipril (3.2% vs. 10.9%, P=0.040). Cardiac MRI showed better reverse remodeling (greater reduction in end‑systolic and end‑diastolic volumes) with ramipril, but no significant difference in myocardial fibrosis. Ramipril reduced heart failure hospitalizations despite not meeting the primary composite.

Fig. 2 Adverse events related to ramipril. (Amat-Santos IJ, et al., 2024)