Highlights from

ACC 2019

American College of Cardiology Annual Scientific Session & Expo

New Orleans 16-18 March 2019

BNP still a reliable prognostic marker before and during sacubitril/valsartan treatment

Despite an initial increase in B-Type Natriuretic Peptide (BNP) after initiation of treatment with sacubitril/valsartan in approximately 60% of patients, it has been assessed that BNP remains a reliable prognostic marker before and during treatment with sacubitril/valsartan [1]. Natriuretic peptides are substrates of neprilysin, and BNP concentrations rise with neprilysin inhibition. This has led to research into the clinical validity of measuring BNP in sacubitril/valsartan-treated patients and the use of N-terminal pro-BNP (NT-proBNP) being preferred and recommended.

Vaduganathan et al. aimed to determine the prognostic performance of BNP before and during treatment with sacubitril/valsartan. Data was analysed from the randomised, double-blind, parallel group, active-controlled PARADIGM-HF trial, which compared the long-term efficacy and safety of sacubitril/valsartan with enalapril in patients with HFrEF [1,2]. BNP measurements were analysed in a central laboratory from frozen venous blood samples drawn before run-in (n=1,656), after run-in with both enalapril and sacubitril/valsartan (time of randomisation, n=2,075 in both study arms), 1 month after randomisation (n=994 in the sacubitril/valsartan arm; n=1,007 in the enalapril arm), and 8 months after randomisation (n=908 in the sacubitril/valsartan arm; n=901 in the enalapril arm).

The researchers assessed the association between both biomarkers and the primary outcome (i.e. cardiovascular death + heart failure hospitalisation) that occurred after each time-point. Median BNP concentration before both run-in phases and any treatment exposure was 202 ng/L (IQR 126-335 ng/L). Median BNP increased to 235 ng/L (IQR 128-422 ng/L) after 8-10 weeks of sacubitril/valsartan, with 18% of patients experiencing a doubling and 6% experienced a tripling of BNP during the first 8-10 weeks; 14% had stable concentrations (approximately 10% change). BNP concentrations at 8-10 weeks of treatment were available in 24% of all patients in the PARADIGM-HF study. In contrast, such striking increases in NT-proBNP following the use of the neprilysin inhibitor were extremely rare. Treatment with sacubitril/valsartan caused a rightward shift in the distribution of BNP compared with NT-proBNP. However, both peptides retained their prognostic accuracy (C-statistics of 63-67% for BNP and C-statistics of 64-70% for NT-proBNP) with no difference between the two biomarkers. Increases in both BNP and NT-proBNP during 8-10 weeks of sacubitril/valsartan were associated with worse outcomes (P=0.003 and P=0.005, respectively). Circulating levels of BNP may increase meaningfully early after initiation of sacubitril/valsartan. As NT-proBNP is less directly influenced by neprilysin inhibition, it may lead to less clinical confusion when measured within 8-10 weeks of starting therapy. However, during treatment, either biomarker predicts the risk of major adverse outcomes in patients treated with angiotensin receptor-neprilysin inhibitors [3].

  1. McMurray JJ, et al. N Engl J Med 2014;371:993-1004.
  2. McMurray JJ, et al. Eur J Heart Fail. 2013;15:1062-73.
  3. Vaduganathan M, et al. Abstract 915-08. ACC 2019, 16-18 March, New Orleans, USA.

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