Sotagliflozin improves outcomes in adults with and without prior CVD
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WASHINGTON — The dual SGLT inhibitor sotagliflozin reduced total CV death, MI and stroke in adults with type 2 diabetes and chronic kidney disease both with and without prior CVD, according to new analyses of the SCORED trial.
The benefits observed with sotagliflozin (approved in the European Union as Zynquista and developed by Lexicon), particularly for MI and stroke, differ from findings seen in other SGLT2 inhibitor trials and may be due to the additional SGLT1 inhibition provided by the drug, Deepak L. Bhatt, MD, MPH, executive director of interventional cardiology programs at Brigham and Women’s Hospital, professor of medicine at Harvard Medical School and Cardiology Today Intervention Section Editor, said during a presentation at the American College of Cardiology Scientific Session.
Previously, sotagliflozin was compared with placebo in SOLOIST, a trial of patients with diabetes and acute decompensated HF. Treatment with sotagliflozin resulted in a significantly lower number of primary endpoint events, which included total CV deaths, hospitalization for HF and urgent HF visits, compared with placebo.
“SCORED compared sotagliflozin vs. placebo with the same primary endpoint, but the difference was instead of patients with acute decompensated HF and diabetes, these were outpatients with diabetes and CKD,” Bhatt said during the presentation. “Interestingly, beyond the HF endpoints, major adverse CV events were significantly reduced with sotagliflozin vs. placebo in the SCORED trial.” See Healio’s previous coverage of SCORED here.
New subgroup analyses
SCORED included 10,584 participants with type 2 diabetes and CKD at risk for CVD. Bhatt reported new subgroup analyses at the ACC Scientific Session that looked at major adverse CV events stratified by history of CVD at baseline, which was defined as prior MI, stroke, coronary revascularization and/or peripheral vascular disease. Endpoints were total MACE, which comprised total CV death, nonfatal MI or nonfatal stroke; total fatal and nonfatal MI; and total fatal and nonfatal stroke.
In the sotagliflozin group, participants with a history of CVD (n = 5,144) saw a 21% decrease in MACE compared with those assigned placebo (HR = 0.79; 95% CI, 0.64-0.96; P = .02). Participants without a baseline history of CVD (n = 5,440) saw a similar benefit compared with placebo (HR = 0.74; 95% CI, 0.56-0.99; P = .046).
Participants assigned sotagliflozin with a history of CVD saw a 31% reduction in total MI (HR = 0.69; 95% CI, 0.51-0.95; P = .023), whereas those without a CVD history saw a 34% reduction in MI events (95% CI, 0.41-1.06; P = .088).
Those in the sotagliflozin group with and without baseline CVD also saw a 31% and 38% reduction in total stroke, respectively, compared with those assigned placebo, with HRs of 0.69 (95% CI, 0.46-1.02; P = .063) and 0.62 (95% CI, 0.36-1.06; P = .08).
Sensitivity analyses with various post hoc definitions of CV disease showed consistent results, Bhatt said.
MACE benefits were also consistent across participants with prior coronary, cerebral or peripheral artery disease.
The trial ended early due to loss of funding. Bhatt said the shortened duration of the trial limited the statistical power to see significant reductions in CV death and limited the magnitude of absolute risk reductions in MACE.
“In patients with diabetes and chronic kidney disease, sotagliflozin significantly reduced the composite of total CV deaths, hospitalizations for HF and urgent HF visits by 26%, with a very early benefit that was significant by 3 months,” Bhatt said. “Total CV deaths, MIs and stroke were reduced by 23%, potentially due to the SGLT1 effect of sotagliflozin on MI and stroke, and this effect was also significant by around 3 months.”
Starting therapy early
In discussion after the presentation, Nasrien E. Ibrahim, MD, FACC, FAHA, FHFSA, advanced heart failure and transplant cardiologist and clinical researcher at Inova Heart and Vascular Institute in Falls Church, Virginia, said the new data show the importance of starting therapy as soon as possible.
“What is most remarkable to me as a HF cardiologist, when we talk about guideline-directed medical therapy implementation, is this early benefit that we see [with sotagliflozin],” Ibrahim said.
Sotagliflozin is approved for people with type 1 diabetes in Europe; FDA declined in 2019 to approve the drug with an indication for adults with type 1 diabetes.
“The messages are strong for the class of SGLT2 inhibitors, irrespective of the fate of this drug,” Bhatt said. “I hope it gets approved; I think it might be the best in the class. It has the HF benefits that the other SGLT2 inhibitors have. They all work in HFrEF and they all work in HFpEF. Starting them early in patients without contraindications is the right thing to do.”
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Bhatt DL, et al. Featured Clinical Research I. Presented at: American College of Cardiology Scientific Session; April 2-4, 2022; Washington, D.C. (hybrid meeting).
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