A Study of Tirzepatide (LY3298176) in Participants With Heart Failure With Preserved Ejection Fraction (HFpEF) and Obesity: The SUMMIT Trial

The KCCQ is a 23-item, participant self-administered questionnaire that assesses impacts of heart failure "over the past 2 weeks" on the following 7 domains:

• Physical Limitation (6)
• Symptom Stability (1)
• Symptom Frequency (4)
• Symptom Burden (3)
• Self-Efficacy (2)
• Quality of Life (3)
• Social Limitation (4)

Each of the 23 individual items are answered on Likert scales of varying lengths (5, 6, or 7-point scales).

KCCQ-CSS includes the symptom and physical limitation domains of the KCCQ. Scores are obtained by averaging the associated individual items and transforming the score to a 0 to 100 range. Higher scores indicate better health status.

Least Square (LS) mean was determined using ANCOVA model with Baseline + HF Decompensation Within 12 Months of Screening + T2DM Status + Baseline BMI group (<35, >=35 kg/m2) + Treatment (Type III sum of squares) as variables .

Clinical Endpoint Committe confirmed Occurrences of CV outcomes were reported here. HF outcomes consisted of cardiovascular death and HF events.

The HF events were defined as worsening clinical symptoms or signs related to HF, which are meaningful to the participant and require intensification of treatment characterized by 1 or more of the following:

• hospitalization for heart failure regardless of duration or treatment received
• use of intravenous drug, usually an intravenous diuretic, but may include intravenous vasodilators or positive inotropic drugs, or
• augmentation or increase in oral diuretic therapy.

Participants performed an exercise capacity assessment using the 6-Minute Walk Test (6MWT) and the distance covered (6MWD) was assessed in meters. The 6MWT was performed indoors on a straight, flat, hard surface that is at least 30 meters in length. The greater distance walked meant better physical capacity.

LS Mean was determined using ANCOVA model with Baseline + HF Decompensation Within 12 Months of Screening + T2DM Status + Baseline BMI group (<35, >=35 kg/m2) + Treatment (Type III sum of squares) as variables.

Percent change in bodyweight was reported. LS mean was determined using ANCOVA model with Baseline + HF Decompensation Within 12 Months of Screening + T2DM Status + Baseline BMI group (<35, >=35 kg/m2) + Treatment (Type III sum of squares) as variables.

Percent change from baseline in hsCRP was reported. LS Mean was determined using ANCOVA model with log (actual measurement/baseline) = log (baseline) + HF decompensation within 12 months of screening + T2DM status + baseline BMI group (<35, >=35 kg/m2) + Treatment (Type III sum of squares) as variables.

Hierarchical Composite Endpoint included time to all-cause death, number of HF events, time to first HF events, KCCQ-CSS, 6MWD.

The winner was determined in each pair-wise comparison in the following order:

• A delayed first occurrence of all-cause death
• If the pair cannot be differentiated based on death, winner has fewer HF events
• If the pair cannot be differentiated by number of HF events, winner has delayed time to occurrence of first HF event
• If the pair still cannot be differentiated, winner has a more favorable category for change from baseline in 6MWD
• If the pair still cannot be differentiated, winner has a more favorable category for change from baseline in KCCQ-CSS
• Otherwise the pair will be recorded as tied.

Reported unit is the total percent of "wins" for each treatment group from performing such a hierarchical comparison across stratification factors in the study.

Percentage of participants with NYHA class change at Week 52 was reported.

All-cause mortality is death due to any cause. Number of participants with time to all-cause mortality are presented.

Number of participants with time to first occurrence of HF events are reported.

Number of HF events and all-cause death are reported.

Number of recurrent HF events were reported.