Integrating High-Sensitivity Troponin T and Sacubitril/Valsartan Treatment in HFpEF: The PARAGON-HF Trial.
Milton Packer M.D.
Gori, M., M. Senni, B. Claggett, J. Liu, A. P. Maggioni, M. Zile, M. F. Prescott, D. J. Van Veldhuisen, F. Zannad, B. Pieske, C. S. P. Lam, J. Rouleau, P. Jhund, M. Packer, M. A. Pfeffer, M. Lefkowitz, V. Shi, J. J. V. McMurray and S. D. Solomon (2021). “Integrating High-Sensitivity Troponin T and Sacubitril/Valsartan Treatment in HFpEF: The PARAGON-HF Trial.” JACC Heart Fail 9(9): 627-635.
OBJECTIVES: This study examined the relationship among high-sensitivity troponin-T (hs-TnT), outcomes, and treatment with sacubitril/valsartan in patients with heart failure (HF) and preserved ejection fraction (HFpEF). BACKGROUND: hs-TnT is a marker of myocardial injury in HF. METHODS: The PARAGON-HF trial randomized 4,796 patients with HFpEF to sacubitril/valsartan or valsartan. We compared the risk of the composite outcome of cardiovascular death (CVD) and total HF hospitalization (HHF) according to hs-TnT. We also assessed the effect of allocated treatment on hs-TnT. RESULTS: hs-TnT was available in 1,141 patients (24%) at run-in (median value: 17 ng/L) and 1,260 (26%) at randomization, with 58.3% having hs-TnT >14 ng/L (upper limit of normal). During a median follow-up of 34 months, there were 393 outcome events (82 CVD, 311 HHF). Adjusting for demographics, comorbidities, left ventricular ejection fraction (LVEF), and N-terminal pro B-type natriuretic peptide (NT-proBNP), log-hs-TnT at randomization was an independent predictor of the composite outcome (HR: 1.38; 95% CI: 1.19-1.59; P < 0.001). Compared with valsartan, sacubitril/valsartan significantly reduced hs-TnT by 9% at week 16 (P < 0.001). Patients whose hs-TnT decreased from randomization to 16 weeks to at or below the median value of 17 ng/L subsequently had a lower risk of CVD/HHF compared with those with persistently elevated hs-TnT (P = 0.046). Patients with higher baseline hs-TnT (>17 ng/L) appeared to have a greater benefit from sacubitril/valsartan treatment when accounting for other potential effect modifiers (P interaction = 0.07). CONCLUSIONS: Higher baseline hs-TnT was associated with increased risk of CVD/HHF, whereas hs-TnT decrease at 16 weeks led to lower subsequent risk of CVD/HHF compared with those who had persistently elevated values. Sacubitril/valsartan significantly reduced hs-TnT compared with valsartan. hs-TnT may be helpful in identifying patients with HFpEF who are more likely to benefit from sacubitril/valsartan.