Abstract 1798: B-type Natriuretic Peptide and the Effect of Ranolazine in Patients with Non-ST Elevation Acute Coronary Syndromes in the MERLIN-TIMI 36 Trial
Ranolazine is believed to exert anti-ischemic effects by reducing myocardial cellular Na+ & Ca2+ overload and consequently LV wall stress. B-type natriuretic peptide (BNP) rises in response to increased wall stress and is a potent indicator of risk in ACS. Thus, we designed a prospective evaluation of the interaction between BNP and the effect of ranolazine as part of a randomized, blinded, placebo-controlled trial.
METHODS: We measured plasma BNP (ADVIA BNP) at baseline (N = 4543) in pts with non-ST elevation ACS randomized to ranolazine or placebo in the MERLIN-TIMI 36 trial. Pts were stratified using BNP >80 pg/ml based on prior work. The 1o endpoint was a composite of cardiovascular death, myocardial infarction, or recurrent ischemia (CVD/MI/RI).
RESULTS: Pts with an elevated BNP (N = 1935) were at significantly higher risk of CVD/MI/RI (26.4% vs. 20.4%, p < 0.0001), CVD/MI (16.2% vs. 7.5%, p<0.0001) and CVD alone (9.0% vs. 2.4%, p<0.0001). In pts with BNP>80 pg/ml, ranolazine reduced the primary endpoint (HR 0.79; 95%CI 0.66 – 0.94, p=0.009) contrasting with the lack of detectable effect in those with a negative BNP result (Figure⇓, p-interaction = 0.05). The apparent effect of ranolazine in pts with BNP>80 pg/ml was directionally similar when considering both recurrent ischemia (HR 0.78; 0.62–0.98; p = 0.04) and CVD/MI (HR 0.83; 0.66–1.05, p= 0.12, p-interaction 0.07).
CONCLUSIONS: Elevated BNP is associated with worse outcomes in ACS. The results of this planned exploratory analysis suggest that ranolazine may have enhanced efficacy in pts with elevated BNP. The potential interaction of biomarkers of hemodynamic stress and the effects of ranolazine warrants additional study.