Association of sodium–glucose cotransporter-2 inhibitors with mortality across the spectrum of myocardial infarction: a systematic review and meta-analysis
Abstract Background The impact of sodium–glucose cotransporter-2 (SGLT2) inhibitors on mortality following myocardial infarction (MI) remains uncertain. Additionally, the role of type 2 diabetes mellitus (T2DM) and heart failure (HF) in modulating the effectiveness of these drugs post-MI are not ful...
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BMC
2025-01-01
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| Series: | Cardiovascular Diabetology |
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| Online Access: | https://doi.org/10.1186/s12933-025-02592-0 |
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| author | Michele Maremmani Ramin Ebrahimi Marco Centola Felice Achilli Valentina Capone Eduardo Bossone Christian Templin Davide Di Vece |
| author_facet | Michele Maremmani Ramin Ebrahimi Marco Centola Felice Achilli Valentina Capone Eduardo Bossone Christian Templin Davide Di Vece |
| author_sort | Michele Maremmani |
| collection | DOAJ |
| description | Abstract Background The impact of sodium–glucose cotransporter-2 (SGLT2) inhibitors on mortality following myocardial infarction (MI) remains uncertain. Additionally, the role of type 2 diabetes mellitus (T2DM) and heart failure (HF) in modulating the effectiveness of these drugs post-MI are not fully understood. This meta-analysis aimed to assess the association of SGLT2 inhibitors with all-cause mortality in post-MI patients and to explore key moderators influencing this benefit. Methods PubMed, Embase, and Scopus were searched for randomized controlled trials (RTCs) and propensity score-matched (PSM) observational studies assessing SGLT2 inhibitors' impact on post-MI mortality. The primary outcome was all-cause mortality. We pooled hazard ratios (HRs) to estimate the intervention's effect on the overall population and stratified studies into early (SGLT2 inhibitors administered within eight weeks post-MI) and delayed treatment trials. Meta-regression assessed the moderating effects of T2DM and HF. Results A total of five RCTs and four PSM observational studies involving 26,753 patients (mean [SD] age, 62.9 [10.5] years; 6,406 female [24.0%]; 16,369 T2DM [61.2%]; 13,933 HF [52.1%]) were included. Early and delayed treatment trials comprised 16,165 (60.4%) and 10,588 (39.6%) patients, respectively. SGLT2 inhibitors reduced all-cause mortality following MI (HR 0.79, 95% CI [0.68, 0.91]; p = 0.001; I2 = 59%). Stratified analysis demonstrated consistent effects in both early (HR 0.76, 95% CI [0.59, 0.98]; p = 0.03; I2 = 65%) and delayed (HR 0.81, 95% CI [0.67, 0.98]; p = 0.03; I2 = 60%) treatment. Meta-regression identified T2DM as a significant moderator of the mortality benefit (β = − 0.0049; p = 0.0006). Conclusion In this meta-analysis, early and delayed treatment with SGLT2 inhibitors following MI was associated with a significant reduction in all-cause mortality. Furthermore, the presence of T2DM was associated with a greater mortality reduction, while HF was not significantly associated with the outcome. Graphical Abstract Association of SGLT2 Inhibitors with Mortality Across the Spectrum of Myocardial Infarction. Data from 26,753 post-MI patients are summarized, including baseline characteristics. The plots represent the pooled hazard ratios (HRs) with 95% confidence intervals (CIs), comparing SGLT2 inhibitors to control (placebo/no treatment), with HRs below 1 favoring SGLT2 inhibitors. The diagram shows early and delayed treatment trial subgroups, presenting the number of participants, the percentage receiving SGLT2 inhibitors, and the respective HRs for mortality. The meta-regression panel highlights T2DM and HF as moderators, reporting β-coefficients (β), p-values, and residual heterogeneity (I2). Negative β (−) indicates that as the percentage of the moderator increases, the HR for mortality decreases. Abbreviations: HF, heart failure; MI, myocardial infarction; SGLT2i, sodium–glucose cotransporter-2 inhibitors; T2DM, type 2 diabetes mellitus. |
| format | Article |
| id | doaj-art-8ddd4b9584e242e6af65922209841f3a |
| institution | Kabale University |
| issn | 1475-2840 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Cardiovascular Diabetology |
| spelling | doaj-art-8ddd4b9584e242e6af65922209841f3a2025-01-26T12:13:45ZengBMCCardiovascular Diabetology1475-28402025-01-0124111410.1186/s12933-025-02592-0Association of sodium–glucose cotransporter-2 inhibitors with mortality across the spectrum of myocardial infarction: a systematic review and meta-analysisMichele Maremmani0Ramin Ebrahimi1Marco Centola2Felice Achilli3Valentina Capone4Eduardo Bossone5Christian Templin6Davide Di Vece7Cardiovascular and Thoracic Department, Pio XI HospitalDepartment of Internal Medicine B, University of Medicine GreifswaldCardiovascular and Thoracic Department, Pio XI HospitalCardiovascular and Thoracic Department, Pio XI HospitalCardiology Division, Antonio Cardarelli HospitalDepartment of Public Health, University of Naples Federico IIDepartment of Internal Medicine B, University of Medicine GreifswaldDepartment of Internal Medicine B, University of Medicine GreifswaldAbstract Background The impact of sodium–glucose cotransporter-2 (SGLT2) inhibitors on mortality following myocardial infarction (MI) remains uncertain. Additionally, the role of type 2 diabetes mellitus (T2DM) and heart failure (HF) in modulating the effectiveness of these drugs post-MI are not fully understood. This meta-analysis aimed to assess the association of SGLT2 inhibitors with all-cause mortality in post-MI patients and to explore key moderators influencing this benefit. Methods PubMed, Embase, and Scopus were searched for randomized controlled trials (RTCs) and propensity score-matched (PSM) observational studies assessing SGLT2 inhibitors' impact on post-MI mortality. The primary outcome was all-cause mortality. We pooled hazard ratios (HRs) to estimate the intervention's effect on the overall population and stratified studies into early (SGLT2 inhibitors administered within eight weeks post-MI) and delayed treatment trials. Meta-regression assessed the moderating effects of T2DM and HF. Results A total of five RCTs and four PSM observational studies involving 26,753 patients (mean [SD] age, 62.9 [10.5] years; 6,406 female [24.0%]; 16,369 T2DM [61.2%]; 13,933 HF [52.1%]) were included. Early and delayed treatment trials comprised 16,165 (60.4%) and 10,588 (39.6%) patients, respectively. SGLT2 inhibitors reduced all-cause mortality following MI (HR 0.79, 95% CI [0.68, 0.91]; p = 0.001; I2 = 59%). Stratified analysis demonstrated consistent effects in both early (HR 0.76, 95% CI [0.59, 0.98]; p = 0.03; I2 = 65%) and delayed (HR 0.81, 95% CI [0.67, 0.98]; p = 0.03; I2 = 60%) treatment. Meta-regression identified T2DM as a significant moderator of the mortality benefit (β = − 0.0049; p = 0.0006). Conclusion In this meta-analysis, early and delayed treatment with SGLT2 inhibitors following MI was associated with a significant reduction in all-cause mortality. Furthermore, the presence of T2DM was associated with a greater mortality reduction, while HF was not significantly associated with the outcome. Graphical Abstract Association of SGLT2 Inhibitors with Mortality Across the Spectrum of Myocardial Infarction. Data from 26,753 post-MI patients are summarized, including baseline characteristics. The plots represent the pooled hazard ratios (HRs) with 95% confidence intervals (CIs), comparing SGLT2 inhibitors to control (placebo/no treatment), with HRs below 1 favoring SGLT2 inhibitors. The diagram shows early and delayed treatment trial subgroups, presenting the number of participants, the percentage receiving SGLT2 inhibitors, and the respective HRs for mortality. The meta-regression panel highlights T2DM and HF as moderators, reporting β-coefficients (β), p-values, and residual heterogeneity (I2). Negative β (−) indicates that as the percentage of the moderator increases, the HR for mortality decreases. Abbreviations: HF, heart failure; MI, myocardial infarction; SGLT2i, sodium–glucose cotransporter-2 inhibitors; T2DM, type 2 diabetes mellitus.https://doi.org/10.1186/s12933-025-02592-0Sodium–glucose cotransporter-2 inhibitorsMyocardial infarctionMortalityDiabetesMeta-analysis |
| spellingShingle | Michele Maremmani Ramin Ebrahimi Marco Centola Felice Achilli Valentina Capone Eduardo Bossone Christian Templin Davide Di Vece Association of sodium–glucose cotransporter-2 inhibitors with mortality across the spectrum of myocardial infarction: a systematic review and meta-analysis Cardiovascular Diabetology Sodium–glucose cotransporter-2 inhibitors Myocardial infarction Mortality Diabetes Meta-analysis |
| title | Association of sodium–glucose cotransporter-2 inhibitors with mortality across the spectrum of myocardial infarction: a systematic review and meta-analysis |
| title_full | Association of sodium–glucose cotransporter-2 inhibitors with mortality across the spectrum of myocardial infarction: a systematic review and meta-analysis |
| title_fullStr | Association of sodium–glucose cotransporter-2 inhibitors with mortality across the spectrum of myocardial infarction: a systematic review and meta-analysis |
| title_full_unstemmed | Association of sodium–glucose cotransporter-2 inhibitors with mortality across the spectrum of myocardial infarction: a systematic review and meta-analysis |
| title_short | Association of sodium–glucose cotransporter-2 inhibitors with mortality across the spectrum of myocardial infarction: a systematic review and meta-analysis |
| title_sort | association of sodium glucose cotransporter 2 inhibitors with mortality across the spectrum of myocardial infarction a systematic review and meta analysis |
| topic | Sodium–glucose cotransporter-2 inhibitors Myocardial infarction Mortality Diabetes Meta-analysis |
| url | https://doi.org/10.1186/s12933-025-02592-0 |
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