Canagliflozin has no effect on SBP variability and associated CV and renal complications: JAHA

The study, published in the Journal of the American Heart Association, showed an association between higher visit‐to‐visit SBP (systolic blood pressure) variability and an increased risk of all-cause mortality and heart failure (HF) hospitalization in type 2 diabetes patients at high cardiovascular risk or with chronic kidney disease (CKD).

The researchers report, "The findings imply that cardiorenal protection with sodium-glucose cotransporter‐2 (SGLT2) inhibitors is unlikely to be substantially mediated by benefits on SBP variability."

SGLT2 inhibitors are reported to reduce systolic blood pressure, but their effect on SBP variability remains unknown. Also, there remains uncertainty regarding the predictive value of SBP variability for different clinical outcomes. Considering this, Robert A. Fletcher, The George Institute for Global Health, UNSW, New South Wales, Sydney, Australia, and colleagues aimed to evaluate whether canagliflozin affects visit‐to‐visit SBP variability in people with type 2 diabetes at high cardiovascular risk or with CKD across 4 study visits over 1.5 years.

They also evaluated the association of SBP variability with kidney, cardiovascular and mortality outcomes using multivariable Cox regression models. The team hypothesized that SGLT2 inhibition might reduce SBP variability, which could contribute to cardiorenal protection. For this purpose, they used individual participant data from the CREDENCE trial and CANVAS Program.

The authors reported the following findings:

• In 11 551 trial participants, canagliflozin modestly lowered the standard deviation of SBP variability (−0.25 mm Hg). Still, there was no effect on the coefficient of variation (0.02%) or variability independent of the mean (0.08 U) when adjusting for correlation with mean SBP.
• Each standard deviation increase in the standard deviation of SBP variability was independently associated with a higher risk of hospitalization for heart failure (hazard ratio [HR], 1.19) and all‐cause mortality (HR, 1.12), with consistent results observed for the coefficient of variation and variability independent of the mean.
• Increases in SBP variability were not associated with kidney outcomes.

"This study represents the largest and most comprehensive analysis of the relationship between SGLT 2 inhibition, systolic blood pressure variability, and clinical outcomes in people with type 2 diabetes," the researchers wrote.

"While canagliflozin lowers systolic blood pressure, it has little to no effect on visit‐to‐visit SBP variability, implying that cardiorenal protection with SGLT2 inhibitors is unlikely to be substantively mediated by benefits on systolic blood pressure variability," they concluded.

Reference:

Fletcher RA, Arnott C, Rockenschaub P, Schutte AE, Carpenter L, Vaduganathan M, Agarwal R, Bakris G, Chang TI, Heerspink HJL, Jardine MJ, Mahaffey KW, Neal B, Pollock C, Jun M, Rodgers A, Perkovic V, Neuen BL. Canagliflozin, Blood Pressure Variability, and Risk of Cardiovascular, Kidney, and Mortality Outcomes: Pooled Individual Participant Data From the CANVAS and CREDENCE Trials. J Am Heart Assoc. 2023 Jun 22:e028516. doi: 10.1161/JAHA.122.028516. Epub ahead of print. PMID: 37345834.