Can neprilysin inhibition improve markers of cardiovascular structure and function in patients with pre-heart failure with preserved ejection fraction?
The PARABLE Randomized Clinical Trial was published online in JAMA Cardiologist on March 8, 2023. In this randomized clinical trial of 250 asymptomatic patients, sacubitril/valsartan vs valsartan was associated with a reduction in blood pressure, pulse pressure, and N-terminal pro-b type natriuretic peptide; an increase in maximal left atrial volume index measured by cardiac magnetic resonance imaging despite lower filling pressures; less decline in kidney function; and fewer serious adverse cardiovascular events.
Among the 250 participants in this study, the median (IQR) age was 72.0 (68.0-77.0) years; 154 participants (61.6%) were men. Most (n = 245 [98.0%]) had hypertension and 60 (24.0%) had type 2 diabetes. Maximal left atrial volume index was increased in patients assigned to receive sacubitril/valsartan (6.9 mL/m2; 95% CI, 0.0 to 13.7) vs valsartan (0.7 mL/m2; 95% CI, −6.3 to 7.7; P < 0.001) despite reduced markers of filling pressure in both groups. Changes in pulse pressure and N-terminal pro-BNP were lower in the sacubitril/valsartan group (−4.2 mm Hg; 95% CI, −7.2 to −1.21 and −17.7%; 95% CI, −36.9 to 7.4, respectively; P <0.001) than the valsartan group (−1.2 mm Hg; 95% CI, −4.1 to 1.7 and 9.4%; 95% CI, −15.6 to 4.9, respectively; P < 0.001). Major adverse cardiovascular events occurred in 6 patients (4.9%) assigned to sacubitril/valsartan and 17 (13.3%) assigned to receive valsartan (adjusted hazard ratio, 0.38; 95% CI, 0.17 to 0.89; adjusted P = 0.04).
However, more work is required to understand the long-term implications.
JAMA Cardiol. Published online March 8, 2023. doi:10.1001/jamacardio.2023.0065
