Abstract Body (Do not enter title and authors here): Background: Intensive systolic blood pressure (SBP) lowering and sodium-glucose cotransport-2 inhibitor (SGLT2i) treatment can reduce the risk of incident heart failure (HF).

Research Question: Based on the American Heart Association Predicting Risk of Cardiovascular Disease Events (PREVENT) estimated risk, what is the modeled number needed to treat (NNT) to a SBP <120 mmHg or with a SGLT2i to prevent an incident diagnosis of HF?

Goal: Estimate the 5-year number needed to treat (NNT₅) to prevent one HF event for intensive systolic blood pressure control and SGLT2i initiation according to PREVENT HF risk.

Methods: Baseline (2000-02) data for 6,034 participants in the Multi-Ethnic Study of Atherosclerosis (MESA) were used to calculate PREVENT HF risk. Mean risk reduction estimates from randomized controlled trials targeting SBP <120 mmHg [38% relative risk reduction (RRR)] and with SGLT2i (31% RRR) were applied to observed HF incidence rates in MESA for NNT₅ calculations across baseline HF risk, as well as N-terminal prohormone of brain natriuretic peptide (NT-proBNP), and diabetes related risk. Low, intermediate, and high 10-year HF risk were defined as <5%, 5-14%, and >15%, respectively.

Results: Mean age was 62 years, 53% were female, 61% were non-white, and 12% had diabetes. The median 10-year PREVENT HF risk was 4%, distributed across individuals with low (52%), intermediate (39%), and high risk (9%). Over 10-year follow-up, there were 198 incident HF cases (3.6 per 1,000 person-years). In the overall sample, the estimated NNT₅ was 112 for intensive SBP control and 199 for SGLT2i. There were large differences in NNT₅ for intensive SBP control and SGLT2i among individuals with low PREVENT HF risk (537 and 768) versus high PREVENT HF risk (34 and 45) (Figure). Among individuals with an intermediate PREVENT HF risk, those with NT-proBNP >125 pg/mL or diabetes had a lower NNT₅ for intensive SBP control (47 and 53) and SGLT2i (64 and 91) compared to those with NT-proBNP <125 pg/mL or without diabetes (intensive SBP control: 209 and 137; SGLT2i: 310 and 183).

Conclusions: Both intensive SBP control and SGLT2i had a stepwise lower NNT₅ to prevent the incident diagnosis of HF across higher PREVENT risk scores, with a lower NNT₅ for intensive SBP control compared to SGLT2i. Incorporation of NTproBNP and DM assessment among intermediate risk persons may further guide allocation of therapies to reduce the risk of HF.