Log in to MyACC
BP and Dapagliflozin in HF With Mildly Reduced or Preserved EF
Quick Takes
- Dapagliflozin provided consistent treatment benefits with respect to cardiovascular events and heart failure-related health status regardless of baseline systolic blood pressure (SBP), and the safety profile of dapagliflozin was similar to placebo across SBP categories.
- These analyses suggest that SBP reduction with dapagliflozin is not responsible for its treatment benefits in heart failure with mildly reduced or preserved ejection fraction.
Study Questions:
What is the interplay between systolic blood pressure (SBP) in heart failure with preserved ejection fraction (HFpEF) and treatment effects of dapagliflozin on SBP and cardiovascular outcomes?
Methods:
The DELIVER (Dapagliflozin Evaluation to Improve the LIVEs of Patients With PReserved Ejection Fraction Heart Failure) trial investigators analyzed 6,263 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 BP-lowering effects of dapagliflozin accounted for its treatment effects by adjusting for the change in SBP from baseline to 1 month. Endpoints studied in this analysis include time to first occurrence of the primary composite outcome (worsening HF episodes [urgent HF visit or HF hospitalization] or cardiovascular death), HF hospitalization, cardiovascular death, and all-cause mortality. For safety assessment, the authors analyzed several adverse events including limb amputation, diabetic ketoacidosis, myocardial infarction, and stroke, among others. To assess whether the change in SBP accounted for the beneficial effects of dapagliflozin, the investigators generated Cox models assessing the relationship between treatment assignment and outcomes adjusting for baseline SBP and change in SBP between baseline and the 1-month visit.
Results:
Average age was 72 ± 10 years and 44% were women. SBP <120 mm Hg was associated with higher HF and mortality events, though amputation and stroke risk increased with higher SBP. Dapagliflozin reduced SBP by 1.8 (95% confidence interval, 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 (pinteraction = 0.15 and 0.98, respectively). Adverse events between arms were similar across SBP categories. The treatment effect was not accounted for by reducing BP.
Conclusions:
The authors concluded that dapagliflozin was similarly efficacious and safe across the range of baseline SBP and its beneficial effects were not accounted for by the changes in SBP.
Perspective:
This subgroup analysis from the DELIVER trial reported that dapagliflozin provided consistent treatment benefits with respect to cardiovascular events and HF-related health status regardless of baseline SBP, and the safety profile of dapagliflozin was similar to placebo across SBP categories. Furthermore, dapagliflozin modestly reduced BP (~2 mm Hg) compared with placebo and the treatment effect was not significantly accounted for by the changes in SBP. These analyses provide new insight into the relationship between SBP and outcomes, and suggest that SBP reduction with dapagliflozin is not responsible for its treatment benefits in HF with mildly reduced or preserved EF. Additional studies are indicated to clarify the mechanisms responsible for the treatment effects of sodium-glucose cotransporter-2 (SGLT-2) inhibitors in patients with HFpEF.
Clinical Topics: Diabetes and Cardiometabolic Disease, Geriatric Cardiology, Heart Failure and Cardiomyopathies, Prevention, Acute Heart Failure
Keywords: Amputation, Blood Pressure, Diabetes Mellitus, Heart Failure, Geriatrics, Metabolic Syndrome, Myocardial Infarction, Secondary Prevention, Sodium-Glucose Transporter 2 Inhibitors, Stroke, Stroke Volume, Vascular Diseases
< Back to Listings
