Robustness of outcomes in trials evaluating sodium–glucose co‐transporter 2 inhibitors for heart failure
Abstract Aims Recent trials have evaluated sodium–glucose co‐transporter 2 inhibitors in patients with heart failure (HF). We sought to assess the robustness of findings from these trials using the fragility index (FI). Methods and results Fragility index is defined as the minimum number of patients...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2022-04-01
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| Series: | ESC Heart Failure |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/ehf2.13785 |
| _version_ | 1811273409350336512 |
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| author | Muhammad Shariq Usman Muhammad Shahzeb Khan Gregg C. Fonarow Stephen J. Greene Tim Friede Muthiah Vaduganathan Gerasimos Filippatos Andrew J. Stewart Coats Stefan D. Anker Javed Butler |
| author_facet | Muhammad Shariq Usman Muhammad Shahzeb Khan Gregg C. Fonarow Stephen J. Greene Tim Friede Muthiah Vaduganathan Gerasimos Filippatos Andrew J. Stewart Coats Stefan D. Anker Javed Butler |
| author_sort | Muhammad Shariq Usman |
| collection | DOAJ |
| description | Abstract Aims Recent trials have evaluated sodium–glucose co‐transporter 2 inhibitors in patients with heart failure (HF). We sought to assess the robustness of findings from these trials using the fragility index (FI). Methods and results Fragility index is defined as the minimum number of patients that must be moved from the ‘non‐event’ to the ‘event’ group to turn a statistically significant result to non‐significant. In addition to FI, fragility quotient [(FQ); FI divided by the sample size] was calculated to assess the proportion of events that must be moved to change the significance. For statistically non‐significant outcomes, reverse fragility index (RFI) and reverse fragility quotient (RFQ) were calculated. Robustness of findings after pooling data from all three trials was also assessed. A robust reduction in first HF hospitalization or cardiovascular mortality was seen with dapagliflozin (FI = 62 and FQ = 0.013), empagliflozin (FI = 50 and FQ = 0.013), and sotagliflozin (FI = 60 and FQ = 0.049). Dapagliflozin nominally improved all‐cause and cardiovascular mortality, with modest FI (n = 8 and 5) and FQ (0.002 and 0.001). Empagliflozin and sotagliflozin did not demonstrate statistically significant reductions in all‐cause mortality, with modest RFI (empagliflozin: RFI = 26 and RFQ = 0.007; sotagliflozin: RFI = 6 and RFQ = 0.005). A similar trend was seen with cardiovascular mortality (empagliflozin: RFI = 24 and RFQ = 0.006; sotagliflozin: RFI = 7 and RFQ = 0.006). Upon meta‐analysis, the result for first HF hospitalization or cardiovascular mortality was robust (FI = 95 and FQ = 0.010). The reductions in all‐cause (FI = 12 and FQ = 0.001) and cardiovascular mortality (FI = 9 and FQ = 0.001), while statistically significant, were fragile. Conclusion Improvement in the composite outcome of first HF hospitalization or cardiovascular death was highly concordant and robust across sodium–glucose co‐transporter 2 inhibitor trials. In contrast, secondary endpoints of all‐cause and cardiovascular mortality were statistically fragile, underscoring the need to power trials for mortality to fully understand the benefit of therapies on fatal events. |
| first_indexed | 2024-04-12T22:58:37Z |
| format | Article |
| id | doaj.art-0f8e31a4617d400987e8af5bf3e7a28a |
| institution | Directory Open Access Journal |
| issn | 2055-5822 |
| language | English |
| last_indexed | 2024-04-12T22:58:37Z |
| publishDate | 2022-04-01 |
| publisher | Wiley |
| record_format | Article |
| series | ESC Heart Failure |
| spelling | doaj.art-0f8e31a4617d400987e8af5bf3e7a28a2022-12-22T03:13:07ZengWileyESC Heart Failure2055-58222022-04-019288589310.1002/ehf2.13785Robustness of outcomes in trials evaluating sodium–glucose co‐transporter 2 inhibitors for heart failureMuhammad Shariq Usman0Muhammad Shahzeb Khan1Gregg C. Fonarow2Stephen J. Greene3Tim Friede4Muthiah Vaduganathan5Gerasimos Filippatos6Andrew J. Stewart Coats7Stefan D. Anker8Javed Butler9Department of Medicine University of Mississippi Jackson MS USADivision of Cardiology Duke University Medical Center Durham NC USADivision of Cardiology Ronald Reagan UCLA Medical Center Los Angeles CA USADivision of Cardiology Duke University Medical Center Durham NC USADepartment of Medical Statistics University Medical Center Göttingen Göttingen GermanyBrigham and Women's Hospital Heart & Vascular Center Boston MA USANational and Kapodistrian University of Athens School of Medicine Athens University Hospital Attikon Athens GreeceDepartment of Cardiology IRCCS San Raffaele Pisana Rome ItalyDepartment of Cardiology (CVK); and Berlin Institute of Health Center for Regenerative Therapies (BCRT); DZHK (German Centre for Cardiovascular Research), partner site Berlin Charité—Universitätsmedizin Berlin Berlin GermanyDepartment of Medicine University of Mississippi Jackson MS USAAbstract Aims Recent trials have evaluated sodium–glucose co‐transporter 2 inhibitors in patients with heart failure (HF). We sought to assess the robustness of findings from these trials using the fragility index (FI). Methods and results Fragility index is defined as the minimum number of patients that must be moved from the ‘non‐event’ to the ‘event’ group to turn a statistically significant result to non‐significant. In addition to FI, fragility quotient [(FQ); FI divided by the sample size] was calculated to assess the proportion of events that must be moved to change the significance. For statistically non‐significant outcomes, reverse fragility index (RFI) and reverse fragility quotient (RFQ) were calculated. Robustness of findings after pooling data from all three trials was also assessed. A robust reduction in first HF hospitalization or cardiovascular mortality was seen with dapagliflozin (FI = 62 and FQ = 0.013), empagliflozin (FI = 50 and FQ = 0.013), and sotagliflozin (FI = 60 and FQ = 0.049). Dapagliflozin nominally improved all‐cause and cardiovascular mortality, with modest FI (n = 8 and 5) and FQ (0.002 and 0.001). Empagliflozin and sotagliflozin did not demonstrate statistically significant reductions in all‐cause mortality, with modest RFI (empagliflozin: RFI = 26 and RFQ = 0.007; sotagliflozin: RFI = 6 and RFQ = 0.005). A similar trend was seen with cardiovascular mortality (empagliflozin: RFI = 24 and RFQ = 0.006; sotagliflozin: RFI = 7 and RFQ = 0.006). Upon meta‐analysis, the result for first HF hospitalization or cardiovascular mortality was robust (FI = 95 and FQ = 0.010). The reductions in all‐cause (FI = 12 and FQ = 0.001) and cardiovascular mortality (FI = 9 and FQ = 0.001), while statistically significant, were fragile. Conclusion Improvement in the composite outcome of first HF hospitalization or cardiovascular death was highly concordant and robust across sodium–glucose co‐transporter 2 inhibitor trials. In contrast, secondary endpoints of all‐cause and cardiovascular mortality were statistically fragile, underscoring the need to power trials for mortality to fully understand the benefit of therapies on fatal events.https://doi.org/10.1002/ehf2.13785Fragility indexRobustnessSodium–glucose co‐transporter 2 inhibitorsCardiac failure |
| spellingShingle | Muhammad Shariq Usman Muhammad Shahzeb Khan Gregg C. Fonarow Stephen J. Greene Tim Friede Muthiah Vaduganathan Gerasimos Filippatos Andrew J. Stewart Coats Stefan D. Anker Javed Butler Robustness of outcomes in trials evaluating sodium–glucose co‐transporter 2 inhibitors for heart failure ESC Heart Failure Fragility index Robustness Sodium–glucose co‐transporter 2 inhibitors Cardiac failure |
| title | Robustness of outcomes in trials evaluating sodium–glucose co‐transporter 2 inhibitors for heart failure |
| title_full | Robustness of outcomes in trials evaluating sodium–glucose co‐transporter 2 inhibitors for heart failure |
| title_fullStr | Robustness of outcomes in trials evaluating sodium–glucose co‐transporter 2 inhibitors for heart failure |
| title_full_unstemmed | Robustness of outcomes in trials evaluating sodium–glucose co‐transporter 2 inhibitors for heart failure |
| title_short | Robustness of outcomes in trials evaluating sodium–glucose co‐transporter 2 inhibitors for heart failure |
| title_sort | robustness of outcomes in trials evaluating sodium glucose co transporter 2 inhibitors for heart failure |
| topic | Fragility index Robustness Sodium–glucose co‐transporter 2 inhibitors Cardiac failure |
| url | https://doi.org/10.1002/ehf2.13785 |
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