Effects of sacubitril/valsartan on hypertensive heart disease: the REVERSE-LVH randomized phase 2 trial

Diffuse interstitial fibrosis is associated with adverse outcomes in hypertensive heart disease and may be reversible. Sacubitril/valsartan could offer greater anti-fibrotic effects than valsartan alone. In the REVERSE-LVH phase 2 open-labelled trial (clinicaltrials.gov NCT: 03553810; funded by the National Medical Research Council of Singapore), 78 patients with essential hypertension and left ventricular hypertrophy (LVH) were randomized 1:1 to sacubitril/valsartan or valsartan for 52 weeks. Primary endpoint was a change in interstitial volume, assessed using cardiovascular magnetic resonance. Despite similar 24-hour systolic blood pressure at 52 weeks (125 ± 11 vs. 126 ± 11 mmHg; P = 0.762), sacubitril/valsartan resulted in a greater absolute reduction in interstitial volume compared to valsartan (−5.2 ± 5.4 vs. −2.5 ± 3.1 mL; P = 0.006). Secondary endpoints showed significant differences favoring sacubitril/valsartan in LV mass, left atrial volume, estimated LV filling pressure, and improved cardiac circulating biomarkers (N-terminal pro-B-type natriuretic peptide and high-sensitivity troponin T). Other markers of cardiac volumes, function and mechanics were similar between the two treatment arms. Here we show the potential myocardial benefits of sacubitril/valsartan beyond blood pressure control, though larger studies are needed to confirm their clinical relevance.