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Background: The effect of vericiguat on sequential N-terminal pro–B-type natriuretic peptide (NT-proBNP) levels and influence of this relationship on clinical outcomes is unknown. Objectives: This study assessed the relationship between changes in NT-proBNP and the primary outcome (cardiovascular death or heart failure hospitalization); evaluated the effect of vericiguat on changes in NT-proBNP; and explored the association between the efficacy of vericiguat and changes in NT-proBNP. Methods: NT-proBNP was measured at randomization and at 16, 32, 48, and 96 weeks in 4,805 of 5,050 patients. The association between NT-proBNP change at week 16 and the primary outcome was assessed. The relationship between changes in NT-proBNP and the primary outcome according to treatment group was assessed by using joint modeling and mediation analysis. Results: A significant and sustained decline in NT-proBNP levels was seen in both treatment groups. After week 16, NT-proBNP levels decreased more with vericiguat vs placebo (any reduction: odds ratio [OR]: 1.45 [95% CI: 1.28-1.65]; P < 0.001; ≥50% reduction: OR: 1.27 [95% CI: 1.10-1.47]; P = 0.001) and were less likely to increase (≥20% increase: OR: 0.68 [95% CI: 0.59-0.78]; P < 0.001; ≥50% increase: OR: 0.70 [95% CI: 0.59-0.82]; P < 0.001). The treatment effect related to serial NT-proBNP on the primary composite outcome was HR: 0.96 (95% CI: 0.95-0.99) at week 16, which increased to HR: 0.90 (95% CI: 0.85-0.96) at week 48; the average extent of mediation of the composite outcome related to NT-proBNP was 45%. Conclusions: In patients with worsening HFrEF, vericiguat significantly decreased NT-proBNP levels compared with placebo. This change appeared associated with a modest relative improvement in the primary outcome of cardiovascular death or heart failure hospitalization.

Background The effectiveness of radial access ( RA ) in ST ‐elevation myocardial infarction ( STEMI ) has been predominantly established in primary percutaneous coronary intervention ( pPCI ) with limited exploration of this issue in the early postfibrinolytic patient. The purpose of this study was to compare the effectiveness and safety of RA versus femoral ( FA ) access in STEMI undergoing either a pharmacoinvasive ( PI ) strategy or pPCI . Methods and Results Within ST rategic Reperfusion Early After Myocardial Infarction ( STREAM ), we evaluated the relationship between arterial access site and primary outcome (30‐day composite of death, shock, congestive heart failure, or reinfarction) and major bleeding according to the treatment strategy received. A total of 1820 STEMI patients were included: 895 PI (49.2%; rescue PCI [n=379; 42.3%], scheduled PCI [n=516; 57.7%]) and 925 pPCI (50.8%). Irrespective of treatment strategy, there was comparable utilization of either access site ( FA : PI 53.4% and pPCI 57.6%). FA STEMI patients were younger, had lower presenting systolic blood pressure, lesser Thrombolysis In Myocardial Infarction risk, and more ∑ ST ‐elevation at baseline. The primary composite endpoint occurred in 8.9% RA versus 15.7% FA patients ( P RA persisted (adjusted odds ratio [ OR ], 0.59; 95% CI , 0.44–0.78; P pPCI (adjusted OR , 0.63; 95% CI , 0.43–0.92) and PI cohorts (adjusted OR , 0.57 95% CI , 0.37–0.86; P interaction=0.730). There was no difference in nonintracranial major bleeding with either access group ( RA vs FA , 5.2% vs 6.0%; P =0.489). Conclusions Regardless of the application of a PI or pPCI strategy, RA was associated with improved clinical outcomes, supporting current STEMI evidence in favor of RA in PCI . Clinical Trial Registration URL : https://www.clinicaltrials.gov/ . Unique identifier: NCT 00623623.