Blood Pressure and Dapagliflozin in Heart Failure With Mildly Reduced or Preserved Ejection Fraction
Year: 2022
Type: article
Abstract: BACKGROUND: Optimizing systolic blood pressure (SBP) in heart failure (HF) with preserved ejection fraction carries a Class I recommendation but with limited evidence. Sodium-glucose cotransporter 2 (SGLT2) inhibitors have antihypertensive effects across cardiovascular disease. OBJECTIVES: The authors examined the interplay between SBP and treatment effects of dapagliflozin on SBP and cardiovascular outcomes. METHODS: The authors analyzed 6,263 DELIVER (Dapagliflozin Evaluation to Improve the LIVEs of Patients With PReserved Ejection Fraction Heart Failure) participants and related baseline and mean achieved SBP categories (<120, 120-129, 130-139, ≥140 mm Hg) to the primary outcome (cardiovascular death or worsening HF), secondary outcomes, and safety events. They analyzed whether the blood pressure-lowering effects of dapagliflozin accounted for its treatment effects by adjusting for the change in SBP from baseline to 1 month. RESULTS: The average age was 72 ± 10 years and 44% were women. SBP <120 mm Hg was associated with higher HF and mortality events, although amputation and stroke risk increased with higher SBP. Dapagliflozin reduced SBP by 1.8 (95% CI: 1.1-2.5) mm Hg compared with placebo at 1 month. The treatment effect of dapagliflozin on the primary outcome and Kansas City Cardiomyopathy Questionnaire total symptom score was consistent across SBP (interaction P = 0.15 and P = 0.98, respectively). Adverse events between arms were similar across SBP categories. The treatment effect was not accounted for by reducing blood pressure. CONCLUSIONS: In DELIVER, risk by SBP was augmented in the lowest and highest categories and varied by endpoint examined. Dapagliflozin modestly decreased SBP compared with placebo. Dapagliflozin was similarly efficacious and safe across the range of baseline SBP. The beneficial effects of dapagliflozin were not accounted for the changes in SBP. (Dapagliflozin Evaluation to Improve the LIVEs of Patients With PReserved Ejection Fraction Heart Failure [DELIVER]; NCT03619213).
Source: JACC Heart Failure
Authors: Senthil Selvaraj, Muthiah Vaduganathan, Brian L. Claggett, Zi Michael Miao, James C. Fang, Orly Vardeny, Akshay S. Desai, Sanjiv J. Shah, Carolyn S.P. Lam, Felipe A. Martinez, Silvio E. Inzucchi, Rudolf A. de Boer, Magnus Petersson, Anna Maria Langkilde, John J.V. McMurray, Scott D. Solomon
Institutions: Duke University, Hospital of the University of Pennsylvania, Duke Medical Center, University of Pennsylvania, Brigham and Women's Hospital, Harvard University, University of Utah, University of Minnesota, Northwestern University, National University of Singapore, National University Heart Centre Singapore, National Heart Centre Singapore, Yale University, Erasmus MC, AstraZeneca (Sweden), University of Glasgow
Language: English
Subfield: Cardiology and Cardiovascular Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,000
Awards: Transition from Risk Factors to Early HF: Prevalence, Pathogenesis, and Phenomics, Deep Phenotyping of the Effects of Therapeutic Ketosis in Heart Failure with Reduced Ejection Fraction, Precision Medicine for Dilated Cardiomyopathy—Novel Assessment of Cardiac Mechanics via Speckle Tracking Echocardiography to Identify Early Phenotypes, Machine learning for the automated identification and tracking of rare myocardial diseases, Determinants, Trajectories, and Consequences of Abnormal Cardiac Mechanics, HeartShare DeCODE-HF: Data translation center to Combine Omics, Deep phenotyping, and Electronic health records for Heart Failure subtypes and treatment targets, Dissecting the Ketone Metabolic Axis in Heart Failure with Reduced Ejection Fraction
OpenAlex ID: W4300002587