Print Share Email Twitter Facebook Linkedin Reddit Get Citation Citation Disclaimer: These citations have been automatically generated based on the information we have and it may not be 100% accurate. Please consult the latest official manual style if you have any questions regarding the format accuracy. AMA Citation Hadley MB, Mechanick JI. Hadley M.B., & Mechanick J.I. Hadley, Michael B., and Jeffrey I. Mechanick. A Novel SGLT-1/2 Inhibitor Reduces Cardiovascular Events: Insights from the Scored and Soloist-WHF Trials. Hurst's the Heart Updates, 11 December 2020. McGraw Hill, 2020. AccessMedicine. https://accessmedicine.mhmedical.com/updatesContent.aspx?gbosid=555020§ionid=252838903APA Citation Hadley MB, Mechanick JI. Hadley M.B., & Mechanick J.I. Hadley, Michael B., and Jeffrey I. Mechanick. (2020). A novel sglt-1/2 inhibitor reduces cardiovascular events: insights from the scored and soloist-whf trials. Fuster V. Fuster V Fuster, Valentin. Hurst's the heart updates. McGraw Hill. https://accessmedicine.mhmedical.com/updatesContent.aspx?gbosid=555020§ionid=252838903.MLA Citation Hadley MB, Mechanick JI. Hadley M.B., & Mechanick J.I. Hadley, Michael B., and Jeffrey I. Mechanick. "A Novel SGLT-1/2 Inhibitor Reduces Cardiovascular Events: Insights from the Scored and Soloist-WHF Trials." Hurst's the Heart Updates Fuster V. Fuster V Fuster, Valentin. McGraw Hill, 2020, https://accessmedicine.mhmedical.com/updatesContent.aspx?gbosid=555020§ionid=252838903. Download citation file: RIS (Zotero) EndNote BibTex Medlars ProCite RefWorks Reference Manager Mendeley © Copyright Tools Clip Full Chapter Figures Only Tables Only Videos Only Supplementary Content A Novel SGLT-1/2 Inhibitor Reduces Cardiovascular Events: Insights from the Scored and Soloist-WHF Trials by Michael B. Hadley, Jeffrey I. Mechanick Listen + +Update to Chapter 28: Diabetes and Cardiovascular Disease Study Summary + +The SOLOIST-WHF and SCORED trials examined the impact of sotagliflozin on cardiovascular events in patients with type 2 diabetes. Sotagliflozin is an inhibitor of sodium-glucose cotransporters (SGLT)-1 and -2 that increases urinary glucose excretion and delays glucose reabsorption in the kidney and gut. Mendelian randomization data has suggested that SGLT-1 inhibition may provide additional cardiovascular benefit beyond that of SGLT-2 inhibition alone. Overall, both trials found that a strategy of sotagliflozin 400mg daily, compared to placebo, significantly reduced the rate of the primary end point of combined cardiovascular death, heart failure hospitalization, and urgent visit for heart failure (see accompanying Hurst’s Central Illustration). Specifically, the SOLOIST-WHF trial investigators enrolled 1222 patients recently hospitalized for heart failure. The rate of primary end point events was 51.0 versus 76.3 per 100 patient-years for the treatment and placebo groups, respectively (HR 0.67, 95% CI 0.52-0.85, P = 0.0009). Significant reductions were also seen in secondary outcomes of combined cardiovascular death and heart failure hospitalization. Similarly, the SCORED trial investigators enrolled 10,584 patients with eGFR of 25-60 ml/min/1.73 m2. The rate of primary end point events was 5.6 versus 7.5 per 100 patient-years for the treatment and placebo groups, respectively (HR 0.74, 95% CI 0.63-0.88, P = 0.0004). A coprimary end point of cardiovascular death, myocardial infarction, or stroke occurred in 8.4% versus 8.9% for the treatment and placebo groups, respectively (HR 0.84, 95% CI 0.72-0.99, P = 0.001). Graphic Jump LocationView Full Size||Download Slide (.ppt) Commentary + +Study Strengths: Both SOLOIST-WHF and SCORED were large, multicenter, randomized, double-blinded, placebo-controlled trials. Most patients had multiple cardiovascular risk factors and were on guideline-directed medical therapy. +Study Limitations: Both studies were ended early due to the COVID-19 pandemic, resulting in median follow-up times of 9 months in SOLOIST-WHF and 16 months in SCORED. The primary end point was thus expanded to include total numbers of events and urgent visits for heart failure. This change may have biased the findings in favor of sotagliflozin. Additionally, the studies were underpowered for secondary outcomes and subgroup analyses (e.g., incident renal failure). Finally, non-white racial/ethnic groups were underrepresented in both studies. +Next Steps/Clinical Perspectives: Multiple studies have established the benefit of SGLT-2 inhibition in reducing cardiovascular events in patients with reduced systolic function, regardless of diabetes. The SOLOIST-WHF trial affirms these findings in a population with median ejection fraction of 35%, while the SCORED trial demonstrates a cardiovascular benefit in patients with a median ejection fraction of 60%. Whether SGLT-2 inhibition provides cardiovascular benefit in patients with preserved ejection fraction is the focus of two forthcoming trials (e.g., DELIVER and EMPEROR-Preserved). +SOLOIST-WHF illustrates that sotagliflozin can be initiated safely at discharge from hospitalization for heart failure. Additionally, these trials affirm that sotagliflozin was beneficial in populations with mild-to-moderately impaired renal function: median eGFR was 50 and 44 ml/min/1.73 m2 in SOLOIST-WHF and SCORED, respectively. Of note, both trials excluded patients with eGFR <25-30 ml/min/1.73 m2. +Whether sotagliflozin, a combined SGLT-1/2 inhibitor, provides significant cardiovascular benefit compared to pure SGLT-2 inhibitors (e.g., dapagliflozin, empagliflozin, and canagliflozin) remains unclear. Head-to-head trials are needed. In the meantime, higher rates of diarrhea observed with sotagliflozin may lead physicians to prefer other SGLT-2 inhibitors. Trial References + + + +Bhatt DL, Szarek M, Steg PG, et al. Sotagliflozin in patients with diabetes and recent worsening heart failure. N Engl J Med. doi: 10.1056/NEJMoa2030183. + +Bhatt DL, Szarek M, Pitt B, et al. Sotagliflozin in patients with diabetes and chronic kidney disease. N Engl J Med. doi: 10.1056/NEJMoa2030186.