Dapagliflozin leads to modest reduction in systolic BP in patients with CKD and albuminuria: Study

In the study published in the American Heart Journal, the placebo-adjusted reduction in systolic BP was evident soon after the initiation of therapy and maintained throughout the trial.

Sodium–glucose cotransporter 2 (SGLT2) inhibitors have emerged as a potent therapy to lower the risk of progressive kidney disease and cardiovascular events in patients with chronic kidney disease. These agents reduce the absorption of sodium and glucose in the proximal tubule, thereby increasing glycosuria and diuresis, typically reducing intravascular volume, which leads to a reduction in blood pressure. However, the consistency and magnitude of BP lowering with dapagliflozin in CKD patients is unknown.

To fill this knowledge gap, Glenn M Chertow, Stanford University School of Medicine, Stanford, California, USA, and colleagues conducted a pre-specified analysis of the DAPA-CKD trial to determine the effect of systolic blood pressure in patients with CKD, with and without type 2 diabetes.

The study included 4304 adults with baseline estimated glomerular filtration rate (eGFR) 25–75 mL/min/1.73m2 and urinary albumin-to-creatinine ratio (UACR) 200–5000 mg/g. They were randomized to either dapagliflozin 10 mg or placebo once daily and followed for a median of 2.4 years.

The study's primary endpoint was a composite of sustained ≥50% eGFR decline, end-stage kidney disease, or death from a cardiovascular or kidney cause. Change in SBP was a pre-specified outcome.

The main findings of the study are as follows:

• The baseline mean SBP was 137.1 mmHg. By Week 2, dapagliflozin compared to placebo reduced SBP by 3.6 mmHg, an effect maintained throughout the trial (2.9 mmHg, 2.3−3.6 mmHg).
• Time-averaged reductions in SBP were 3.2 mmHg in patients with diabetes and 2.3 mmHg in patients without diabetes.
• The time-averaged effect of dapagliflozin on diastolic blood pressure (DBP) was 1.0 mmHg; 0.8 mmHg in patients with diabetes and 1.4 mmHg in patients without diabetes.
• The benefits of dapagliflozin on the primary composite and secondary endpoints were evident across the spectrum of baseline SBP and DBP.

The findings show that randomization to dapagliflozin in patients with chronic kidney disease and albuminuria is associated with modest reductions in systolic and diastolic BP. 

The magnitude reduction in systolic blood pressure was observed to be similar to that provided by several commonly prescribed antihypertensive agents or following renal denervation.

"These findings should inform clinical decisions undertaken when aiming to optimize control of hypertension in CKD patients," the researchers concluded. 

Reference:

Heerspink, H. J., Provenzano, M., Vart, P., Jongs, N., Correa-Rotter, R., Rossing, P., Mark, P. B., Pecoits-Filho, R., McMurray, J. J., Langkilde, A. M., Wheeler, D. C., Toto, R. B., & Chertow, G. M. (2024). Dapagliflozin and Blood Pressure in Patients with Chronic Kidney Disease and Albuminuria. American Heart Journal. https://doi.org/10.1016/j.ahj.2024.02.006