Effects of sacubitril/valsartan versus olmesartan on left atrial structure in hypertensive patients without HFrEF: a randomized controlled trial

Background and purpose: Treatment with sacubitril plus valsartan attenuates cardiac remodeling in patients with heart failure with reduced ejection fraction (HFrEF). Evidence for potential effects of sacubitril/valsartan on left atrial remodeling in hypertensive patients without HFrEF, however, is limited. Therefore, we aimed to compare the effects of sacubitril/valsartan and olmesartan on the left atrial structure in Chinese hypertensive patients. Methods: This single-center randomized controlled trial was conducted at Nanjing First Hospital from June 2021 to February 2022. Adult patients (18–80 years of age) with essential hypertension but no HFrEF were randomized at a 1:1 ratio to receive sacubitril/valsartan or olmesartan. Initial dosage was 100 mg/day for sacubitril/valsartan and 20 mg/day for olmesartan. In patients who did not reach the target blood pressure (<140/90 mmHg) within a week, dosage was increased to 200 to 400 mg/day for sacubitril/valsartan and 40 mg/day for olmesartan. In patients who failed to reach the target blood pressure at 4 weeks, other antihypertensive drugs were used at physician’s discretion. The patients should reach the target blood pressure at 8 weeks. The primary endpoint was the change of left atrial volume index (LAVI) from baseline to 24 weeks. Secondary endpoints included the changes of left atrial diameter (LAD), left atrial emptying fraction (LAEF), left ventricular ejection fraction (LVEF), and left ventricular end-diastolic diameter (LVEDD) from baseline to 24 weeks. Results are shown as median and interquartile range (IQR). Results: A total of 153 patients were enrolled. The final analysis included 145 patients who completed the 24-week assessment: 71 and 74 in the sacubitril/valsartan and olmesartan groups, respectively. Demographic and key baseline characteristics (e.g., blood pressure) were comparable between the 2 groups. Target blood pressure was achieved in all 145 patients at 8 weeks. In comparison to the olmesartan group, the sacubitril/valsartan group had significantly greater change in LAVI (−4.19 [−2.87, −5.43] vs. −0.61 [−0.53, −1.13] mL/m2, P < 0.001), LAEF (1.00% [2.00%, 0%] vs. 0% [1.00%, −1.00%], P = 0.014), LVEDD (−2.00 [0, −3.00]mm vs. −1.00 [0, −1.00]mm, P < 0.001), and LVEF (1.00% [3.00%, 1.00%] vs. 0% [1.00%, 0%], P < 0.001), but not LAD, LAVI, LAEF, LVEDD, and LVEF at 24 weeks relative to the baseline. Conclusions: In comparison to olmesartan, sacubitril/valsartan resulted in more robust improvements in left atrial and ventricular structure and function in hypertensive patients without HFrEF.