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Cardiovascular Biomarkers in PIONEER-HF Trial
Study Questions:
How does sacubitril/valsartan impact high-sensitivity troponin T (hsTnT), soluble ST2 (sST2), and urinary cyclic guanosine 3′5′ monophosphate (cGMP) levels compared to enalapril in patients with heart failure and reduced ejection fraction (HFrEF)?
Methods:
This is a nested biomarker substudy in which hsTnT, sST2, and urinary cGMP were measured in 694 participants (n = 342 in the sacubitril/valsartan arm and 352 in the enalapril arm) of the PIONEER-HF trial at baseline, 1, 2, 4, and 8 weeks. PIONEER-HF was a randomized trial comparing sacubitril/valsartan to enalapril in patients with HFrEF (EF ≤40% with elevated B-type natriuretic peptide [BNP] or N-terminal pro-BNP [NT-proBNP] levels) admitted with acute decompensated HF. The authors assessed the effect of sacubitril/valsartan and enalapril on the change in hsTnT, sST2, and urinary cGMP levels, and determined whether biomarker levels were associated with outcomes (cardiovascular death or rehospitalization for HF).
Results:
Overall, participants were 73% male, 35% black, and median age was 62 years. Compared with enalapril, sacubitril/valsartan led to a significantly greater decline in hsTnT and sST2, with a 16% greater reduction in hsTnT (p < 0.001) and 9% greater reduction in sST2 by 4 weeks, compared to the enalapril group. Urinary cGMP increased with sacubitril/valsartan close to 50% relative to baseline, while levels with enalapril showed a small decrease. Baseline levels of hsTnT and sST2 were associated with outcomes only in the enalapril group.
Conclusions:
Both enalapril and sacubitril/valsartan were associated with changes in hsTnT, sST2, and urinary cGMP levels, with a greater magnitude in the sacubitril/valsartan arm. Baseline biomarker levels were associated with outcomes.
Perspective:
This study confirms that biomarkers of myocardial stress can be modified by pharmacologic therapies. The changes in hsTnT, sST2, and urinary cGMP were noted within a week of initiation, suggesting that the impact of these therapies occur rapidly, and supporting earlier rather than delayed intervention. The study does not show whether the magnitude of change in biomarker levels is associated with outcomes. Evidence of an improvement in outcomes that correlates with the change in levels would support the use of these markers as surrogate measures of benefit.
Keywords: Biomarkers, Enalapril, Guanosine Monophosphate, Heart Failure, Natriuretic Peptide, Brain, Outcome Assessment, Health Care, Peptide Fragments, Stroke Volume, Troponin, Troponin T
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