Development of a 3D bioengineered human lung submucosal gland ductal airway model to study mucociliary clearance in vitro.

BACKGROUND AND PURPOSE: Resistant hypertension (RH) is mechanistically driven largely by perturbations in renin-aldosterone, rife among stroke survivors, and portends a poorer prognosis in this population. We sought to evaluate the feasibility of a physiological profiling strategy using plasma renin and aldosterone to tailor medical therapy to control BP among stroke survivors with uncontrolled RH.

METHODS

This was a pilot randomized clinical trial. We enrolled stroke survivors aged ≥18 years with uncontrolled blood pressure on at least 3 antihypertensive medications at full doses at a tertiary hospital in Ghana. Participants were enrolled between June 16, 2023, and April 19, 2024, and the last participant completed follow-up on October 30, 2024. Participants randomized to the physiologic profiling arm had plasma renin activity and aldosterone levels measured and eplerenone, a mineralocorticoid receptor antagonist, or amiloride was added to their existing BP medications depending on renin-aldosterone profile. Those assigned to the control arm received usual care where physicians added antihypertensive agents as indicated. The primary clinical outcome was proportions with blood pressure < 140/90 mmHg at month 6, by intention-to-treat.

RESULTS

Among 60 eligible participants, 30 each were randomized to either the intervention or control arms, 53 % were female, mean (SD) age of 58.4 (10.3) years. The trial was feasible to implement. Primary outcome was achieved in 19 (63.3 %) in the intervention arm vs. 11 (36.7 %) in the usual care arm, p = 0.04. There were 3 major adverse cardiovascular events during follow-up, 1 (3.3 %) non-fatal recurrent stroke in the intervention arm vs 2 (6.7 %) cardiovascular deaths in the usual care arm, p = 0.55. No medication-related adverse events were reported.

CONCLUSIONS

Among Ghanaian stroke survivors with RH, the addition of eplerenone to background antihypertensive medications based on plasma renin-aldosterone profile demonstrated a signal of efficacy compared with usual care. A larger study with longer follow-up powered to assess hard cardiovascular outcomes among stroke survivors with uncontrolled resistant hypertension is warranted.