SGLT2 Inhibition Across a Range of Left Ventricular Hypertrophy, with Muthiah Vaduganathan, MD, MPH

An analysis of the DELIVER trial from the American College of Cardiology 2024 (ACC.24) Annual Scientific Sessions is providing clinicians with new insight into the effects of SGLT2 inhibition across the range of left ventricular hypertrophy among patients with a left ventricular ejection fraction (LVEF) greater than 40%.

Presented by Muthiah Vaduganathan, MD, MPH, codirector of the Center for Cardiometabolic Implementation Science at Brigham and Women’s Hospital, results of the suited demonstrate use of dapagliflozin provided consistent benefit for event reductions and was well-tolerated in patients with heart failure across a range of left ventricular hypertrophy.

“One of the inclusion criteria was left ventricular hypertrophy. The other being enlarged, left atrium. So, a substantial number of patients in DELIVER actually had evidence of left ventricular remodeling with hypertrophy,” explained Vaduganathan in an interview with HCPLive. “And so, it gave us this unique opportunity to examine the association between LVH and the degree of LVH with subsequent risk as well as responsiveness to medical therapies.”

A multicenter, parallel-group, event-driven, double-blind, randomized, controlled trial conducted at 353 centers in 20 countries, the DELIVER trial randomized 6263 patients in a 1:1 ratio to dapagliflozin or placebo therapy for a composite endpoint of cardiovascular death or worsening heart failure event. Upon analysis, results of the trial indicated use of dapagliflozin was associated with an 18% relative risk reduction for the composite endpoint (Hazard Ratio [HR], 0.82; 95% Confidence Interval [CI], , 0.73-0.92]; P <.001) Further analysis demonstrated use of dapagliflozin was associated with a 21% reduction in risk of worsening heart failure (HR, 0.79; 95% CI, 0.69-0.91) and a 12% reduction in risk for cardiovascular mortality (HR, 0.88; 95% CI, 0.74-1.05).²

From the trial, investigators identified 3988 patients with available measurements for septal wall thickness (SWT) and posterior wall thickness (PWT). Of note, the mean SWT was 1.3±0.2cm and the mean PWT was 1.2±0.2cm. investigators also pointed out 93% of the cohort had a history of hypertension.¹

Upon analysis, investigators identified a linear association between SWT(adjusted hazard ratio [aHR] per 1 SD, 1.06; 95% Confidence Interval [CI], 1.01 to 1.12; P =.025) and PWT (aHR per 1 SD, 1.09; 95% CI, 1.04 to 1.15; P < .001) with risk of the trial’s primary composite outcome. Further analysis indicated hypertension did not modify this relationship for SWT (P for interaction=.904) or PWT (P for interaction=.540).¹

However, investigators noted a relatively low number of patients had more significant left ventricular without a history of hypertension (n=98 with any wall thickness ≥1.3cm and n=35 ≥1.5cm).In their conclusion, investigators pointed out the benefits of dapagliflozin on the primary outcome were consistent across ranges of SWT (P for interaction= .246) and PWT (P for interaction= .472).¹

For more on this study and how it informs use of dapagliflozin, check out our interview with Vaduganathan from ACC.24.

Relevant disclosures for Vaduganathan include Amgen, AstraZeneca, Bayer AG, Boehringer Ingelheim Pharmaceuticals, Cytokinetics, Lexicon, and others.

References:

1. Vaduganathan M, Claggett B, Kulac I, et al. DAPAGLIFLOZIN IN PATIENTS WITH HEART FAILURE ACROSS A RANGE OF LEFT VENTRICULAR HYPERTROPHY IN THE DELIVER TRIAL. Presented at: American College of Cardiology (ACC.24) Annual Scientific Session. April 6 – 8, 2024. Atlanta, GA.
2. Campbell P. Dapagliflozin proves HFPEF benefit in deliver trial. HCP Live. August 27, 2022. Accessed April 7, 2024. https://www.hcplive.com/view/dapagliflozin-proves-hfpef-benefit-in-deliver-trial.