Diffuse interstitial fibrosis is a key contributor to adverse outcomes in hypertensive heart disease and may be reversible. Sacubitril/valsartan, a combined angiotensin receptor- neprilysin inhibitor, may offer superior anti-fibrotic effects compared to valsartan alone. The REVERSE-LVH phase 2 open-label trial (clinicaltrials.gov NCT: 03553810), funded by the National Medical Research Council of Singapore, investigated the myocardial benefits of sacubitril/valsartan in patients with essential hypertension and left ventricular hypertrophy (LVH).
In this randomized, open-label study, 78 patients with essential hypertension and LVH were assigned in a 1:1 ratio to receive either sacubitril/valsartan or valsartan alone for 52 weeks. The primary endpoint was the change in interstitial volume, assessed using cardiovascular magnetic resonance (CMR) imaging. Secondary endpoints included changes in left ventricular (LV) mass, left atrial volume, estimated LV filling pressure, and cardiac circulating biomarkers, including N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity troponin T (hs-TnT). Other measures of cardiac volumes, function, and mechanics were also evaluated.
At 52 weeks, both treatment groups achieved similar 24-hour systolic blood pressure control (125 ± 11 mmHg for sacubitril/valsartan vs. 126 ± 11 mmHg for valsartan; P = 0.762). However, sacubitril/valsartan led to a significantly greater reduction in interstitial volume compared to valsartan (−5.2 ± 5.4 mL vs. −2.5 ± 3.1 mL; P = 0.006). Secondary endpoints also favored sacubitril/valsartan, with significant reductions in LV mass, left atrial volume, and estimated LV filling pressure, as well as improvements in NT-proBNP and hs-TnT levels. Other markers of cardiac volumes, function, and mechanics showed no significant differences between the two groups.
Sacubitril/valsartan demonstrated greater anti-fibrotic effects and improvements in key cardiac parameters compared to valsartan in patients with hypertension and LVH, independent of blood pressure control. These findings suggest potential myocardial benefits of sacubitril/valsartan, but larger, multicenter trials are needed to confirm the clinical significance of these results and their impact on long-term outcomes in hypertensive heart disease.
