Sotagliflozin shows ‘consistent’ HFpEF benefit in new SCORED/SOLOIST analysis
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The dual SGLT inhibitor sotagliflozin reduced risk for total CV death, HF hospitalization and urgent HF visits across the full range of ejection fraction, including preserved EF, data from a pooled analysis showed.
Compared with placebo, sotagliflozin, a dual SGLT 1/2 inhibitor (approved in the European Union as Zynquista and developed by Lexicon), also demonstrated a significant reduction in CV death in on-treatment analyses, Cardiology Today Intervention Section Editor Deepak L. Bhatt, MD, MPH, executive director of interventional cardiology programs at Brigham and Women’s Hospital and professor of medicine at Harvard Medical School, said during a presentation at the American College of Cardiology Scientific Session.
The randomized data are the first from a prespecified analysis to show a significant effect of a therapy on HFpEF, additionally demonstrating a consistent benefit in women, Bhatt said.
“We found a consistent, significant benefit across the full range of EF, including HF with reduced EF, HF with midrange EF and HFpEF, each showing a consistent benefit,” Bhatt told Healio. “In the overall trial, irrespective of EF, there was a significant benefit in reducing the total composite of CV death, hospitalization for HF and urgent HF visits.”
Patient-level data
There are growing data with respect to the benefits of SGLT2 inhibitors in the prevention and treatment of HF, Bhatt said during a presentation. The most recent additions are the SOLOIST-WHF and SCORED trials. SOLOIST studied 1,222 adults with diabetes and acute decompensated HF (reduced or preserved EF) admitted to the hospital, who received sotagliflozin or placebo. SCORED studied 10,584 stable patients with diabetes and chronic kidney disease, also randomly assigned sotagliflozin or placebo. In SCORED, two-thirds of participants had no history of HF.
As Healio previously reported, the SOLOIST-WHF and SCORED trials showed adults with type 2 diabetes and worsening HF or at CV risk who received sotagliflozin experienced reduced risk for CV death and hospitalization or urgent visits for HF compared with placebo. The data were presented at the American Heart Association Scientific Sessions in November.
In a prespecified, pooled analysis of patient-level data from SOLOIST and SCORED, researchers examined the effectiveness of sotagliflozin treatment according to differences in baseline EF; these data were available for all but 22 patients in the original trials.
Researchers analyzed the entire pooled cohort of 11,784 patients and a subgroup of 4,500 patients with a history of HF. Among both groups, they found significant reductions in the risk of CV death, HF hospitalization or urgent HF visits, irrespective of baseline EF.
‘Big leap forward’ for HFpEF
Among 1,758 patients in both trials with an EF of 40% or less, sotagliflozin reduced risk for the composite endpoint of total CV death, HF hospitalization and urgent HF visits by 22% (HR = 0.78; 95% CI, 0.63-0.96; P = .02). For 456 patients with midrange EF, defined post hoc as an EF of 40% to 50%, sotagliflozin reduced risk by 39% for the pooled cohort (HR = 0.61; 95% CI, 0.4-0.94; P = .02). For 739 participants with HFpEF, sotagliflozin reduced risk by 37% for the pooled cohort (HR = 0.63; 95% CI, 0.45-0.89; P = .009).
Participants in SCORED with no HF history (n = 6,738) experienced a 27% risk reduction for the primary endpoint (HR = 0.73; 95% CI, 0.54-0.99; P = .04).
“Across the full range of EF, benefit was consistent ... a statistically significant finding in each of those subgroups,” Bhatt said in an interview. “This included patients with HFpEF, showing for the first time in randomized data from a prespecified analysis of clinical trials a significant effect in HFpEF.”
In analyses stratified by sex, data also showed a consistent benefit for both sexes, particularly for women with normal EF, Bhatt said.
“This is a big leap forward in our potential approaches with HFpEF, applicable both to men and women,” Bhatt told Healio.
In on-treatment analyses, Bhatt noted a significant reduction in CV death among all participants.
“In the overall trials, pooled together, CV death was lower but not statistically significant, likely because the trials ended earlier than planned because of COVID-19-related financial issues,” Bhatt told Healio. “That truncated follow-up for endpoints like CV death, so even though rates were lower, it wasn’t statistically significant.”
Both SCORED and SOLOIST were stopped early due to the pandemic; however, robust reductions in the primary endpoints were observed in both trials and in the pooled analyses, Bhatt said.
“The shortened duration of follow-up eliminated the statistical power to see significant reductions in certain endpoints, though on-treatment analyses did show a significant reduction in CV death in the overall population, as well as those with a history of HF,” Bhatt said during the presentation.
More HFpEF data coming
Bhatt said the results from SCORED and SOLOIST likely apply to the SGLT2 inhibitor class; however, more data about HFpEF in those with and without diabetes are coming.
Two large trial programs are exploring the benefits of SGLT2 inhibitors in HFpEF. EMPEROR-Preserved is assessing the effects of empagliflozin (Jardiance, Boehringer Ingelheim/Eli Lilly) related to CV death or hospitalization of adults with HFpEF. DELIVER is assessing the effect of dapagliflozin (Farxiga, AstraZeneca) on reducing CV death or worsening HF of adults with HFpEF. Both trials include participants with and without diabetes; results from both trials are expected in the near future.
“The key message is this is the first analysis of clinical trials to show a significant effect of a therapy on HFpEF, demonstrating a consistent and significant benefit in women,” Bhatt told Healio. “Even beyond these data, one could argue if a patient has diabetes and HFpEF, they should likely be prescribed an SGLT2 inhibitor anyway. Barring issues of cost, access or contraindications, I would say most patients with diabetes with any form of HF — or at risk for HF — should be prescribed SGLT2 inhibitor therapy.”
Perspective
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Javed Butler, MD, MPH, MBA, FACC, FAHA
In this combined analysis of the SCORED and SOLOIST trials, the investigators show detailed data on outcomes of patients according to ejection fraction, sex and history of HF. Consistent with the previous individual trial data, robust outcomes benefits were seen across all groups.
The data for benefit with SGLT2 inhibitors in patients with HFrEF is now well established; however, trials in those with HFpEF are ongoing. These data from SOLOIST and SCORED are the first large, randomized data to show benefit in outcomes with patients with HF with midrange EF and HFpEF. Unfortunately, the trials were stopped early during the pandemic; full enrollment and follow-up did not occur. Nevertheless, the outcomes data are impressive.
These data support the role of sotagliflozin in patients with characteristics of those enrolled in the SCORED and SOLOIST trials. Whether there is incremental benefit of SGLT1 inhibition in addition to SGLT2 inhibition needs further study. Also, data on the use of sotagliflozin in patients without diabetes are not available.
These data are encouraging; however, definitive use of these agents in HFpEF will require the results of the two large outcomes trials that are ongoing: EMPEROR-Preserved and DELIVER.
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Bhatt DL, et al. Late-Breaking Clinical Trials IV. Presented at: American College of Cardiology Scientific Session; May 15-17, 2021 (virtual meeting).
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