ASCVD risk refinement with NT-proBNP for statin allocation among low- and intermediate risk individuals

Background Statin trials targeting low- to intermediate risk individuals, namely MEGA, JUPITER, and HOPE-3, have demonstrated benefit of statin use for primary prevention of atherosclerotic cardiovascular disease (ASCVD), but are poorly reflected in guideline recommendations for primary prevention of ASCVD. N-terminal pro-B-type natriuretic peptide (NT-proBNP) may refine ASCVD risk in low-to intermediate risk individuals eligible for HOPE-3, JUPITER and MEGA, and aid statin initiation in low- to intermediate risk populations. Methods 5434 participants, aged 45 years and above from the prospective population-based Rotterdam Study, free of ASCVD, heart failure, and diabetes, were included between 1997 and 2008. Eligibility criteria for MEGA, JUPITER, and HOPE-3 trials were checked for each participant. ASCVD event rates, hazard ratios (HR), 5-year numbers needed to treat (NNT 5y ), and screen (NNS 5y ) per trial eligible population and NT-proBNP category (≤50, 50-100, and >100 pg/mL) were calculated. Results Median age was 61.6 years, 58.9% were women, median NT-proBNP was 60 pg/mL. The proportions of participants eligible for MEGA, JUPITER and HOPE-3 were 34.9%, 10.4% and 23.7%. Incidence rates per 1000 person-years for ASCVD were 10.4 (95%CI: 60.1-67.9) for MEGA, 16.8 (95%CI: 13.6-20.6) for JUPITER, and 12.1 (95%CI: 10.3-14) for HOPE-3. Adjusted HR in trial eligible individuals for NT-proBNP >100 pg/mL compared to ≤50 pg/mL level were 1.73 (95%CI: 1.21-2.47), 1.46 (95%CI: 0.80-2.66) and 1.50 (95%CI: 0.99-2.26), respectively. Estimated NNT 5y among trial eligible individuals with NT-proBNP levels >100 pg/mL based on high-intensity statin treatment, varied from 23 to 34 to prevent one ASCVD event, while NNS 5y ranged between 56 and 134. Conclusions NT-proBNP level >100 pg/mL identifies individuals at the highest ASCVD risk among low- to intermediate risk populations who are likely to benefit from statin treatment at acceptable NNT 5y and NNS 5y . Clinical Perspective What is New? NT-proBNP level >100 pg/mL can identify individuals at the highest ASCVD risk among low- to intermediate risk populations who are likely to benefit from statin treatment at acceptable numbers needed to treat and screen. Among apparently healthy individuals without prior ASCVD and diabetes mellitus, 60% was deemed to be at low- to intermediate risk by qualifying for at least one of three RCT based on the trial eligibility criteria, and one out four individuals had NT-proBNP level >100 pg/mL. What are the Clinical Implications? NT-proBNP level can be used for risk refining in low- to intermediate risk individuals who are most likely to benefit from statin initiation for ASCVD primary prevention.