Levels of natriuretic peptides related to therapeutic effect and CV outcomes in HFpEF patients
Interaction Between Spironolactone and Natriuretic Peptides in Patients With Heart Failure and Preserved Ejection Fraction
From the TOPCAT TrialLiterature - Anand IS, Claggett B, Liu J, et al. - JACC, 2017;5(4):241-252
- At baseline, American patients with higher NP levels were older and more likely to have atrial fibrillation, chronic kidney disease, microalbuminuria and lower albumin and less likely to be obese.
- Primary endpoint occurred in 21.5% of patients.
- The incidence rate for outcomes increased across NP tertiles: event rates were 5.9, 6.3 and 106/100 patients years, respectively.
- HRs primary endpoint for second and third tertile were 1.01 (95% CI 0.65-1.58, P=0.95) and 1.89 (95% CI 1.25-2.84, P=0.002) respectively, compared to first tertile. A similar trend was observed when all-cause mortality and HF hospitalization were analysed separately.
- When BNP and NT-proBNP values were analysed together using z-scores based on continuous values, HRs were 1.41 (95% CI 1.20-1.65, P<0.001), 1.48 (95% CI 1.25-1.76, P<0.001) and 1.49 (95% CI 1.24-1.78, P<0.001) for the primary endpoint, all-cause mortality and HF hospitalization.
- The effect of spironolactone corresponded to an HR of 0.64 (95% CI 0.46-0.90, P<0.01) for the primary endpoint. Most of this beneficial effect was restricted to the lowest NP tertile and the interaction between this effect and the tertile grouping of NT levels was significant (P=0.017). A similar effect was observed using z-scores and when also Russian/Georgian people were included.
- A higher NP tertile was associated with worse left ventricle diastolic function.
Using either continuous NP values or NP values grouped by tertiles, NP values were independently associated with an increased risk for the composite of cardiovascular death, HF hospitalization and aborted cardiac arrest in HFpEF patients. This confirms previous findings that NPs are important prognostic markers in patients with HFpEF. In addition, there was a significant interaction between the effect of spironolactone and NP levels, with most of the beneficial effects seen in lower-risk patients with low NP levels, in contrast to high NP levels. This suggests that patients at higher risk are not always more likely to benefit from treatment. Thus, the strategy of using elevated plasma concentrations of NPs as a patient selection criterion in trials of HFpEF needs to be re-examined in prospectively designed clinical trials.