Dapagliflozin safely improves outcomes in people with apparent treatment-resistant hypertension: DELIVER Trial

Apparent treatment-resistant hypertension is defined as BP ≥140/90 mm Hg (≥130/80 mm Hg if diabetes) despite treatment with 3 antihypertensive drugs including a diuretic.

Apparent treatment-resistant hypertension is prevalent and associated with adverse outcomes in heart failure (HF) with mildly reduced or preserved ejection fraction. In the DELIVER trial, aTRH was identified in >1 in 10 patients with HF and left ventricular ejection fraction >40%. In this high-risk population, not much is known about the potential role of sodium-glucose co-transporter 2 inhibition.

In the analysis of the DELIVER trial (Dapagliflozin Evaluation to Improve the Lives of Patients with Preserved Ejection Fraction Heart Failure), John W. Ostrominski, Cardiovascular Division, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, and colleagues evaluated treatment effects and clinical profiles of dapagliflozin among participants with aTRH.

For the analysis, DELIVER participants were divided based on baseline blood pressure (BP). Nonresistant hypertension was defined as BP above the threshold but not meeting TRH criteria. Controlled BP was defined as BP under threshold.

Incidence of the primary outcome (worsening heart failure event or cardiovascular event), safety events, and key secondary outcomes were evaluated by baseline BP category.

The analysis led to the following findings:

• Among 6263 DELIVER participants, 60.1% had controlled BP, 28.4% had nonresistant hypertension, and 11.5% had aTRH at baseline.
• Participants with aTRH had more cardiometabolic comorbidities and tended to have higher left ventricular ejection fraction and worse kidney function.
• Rates of the primary outcome were 8.7 per 100 patient-years in those with controlled BP, 8.5 per 100 patient-years in the nonresistant hypertension group, and 9.5 per 100 patient-years in the aTRH group. Relative treatment benefits of dapagliflozin versus placebo on the primary outcome were consistent across BP categories.
• Participants with aTRH exhibited the greatest absolute reduction in the rate of primary events with dapagliflozin (4.1 per 100 patient-years) compared with nonresistant hypertension (2.7 per 100 patient-years) and controlled BP (0.8 per 100 patient-years).
• Irrespective of assigned treatment, participants with aTRH experienced a higher rate of reported vascular events, including myocardial infarction and stroke, over study follow-up.
• Dapagliflozin modestly reduced systolic BP (by ≈1 to 3 mm Hg) without increasing the risk of hypotension, hypovolemia, or other serious adverse events, irrespective of BP category, but did not improve the proportion of participants with aTRH attaining goal BP over time.

"Dapagliflozin consistently improved clinical outcomes and was well-tolerated, including among those with apparent treatment-resistant hypertension," the researchers concluded.

Reference:

Ostrominski, John W., et al. "Dapagliflozin and Apparent Treatment-Resistant Hypertension in Heart Failure With Mildly Reduced or Preserved Ejection Fraction: the DELIVER Trial." Circulation, 2023.