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

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.