Sodium Glucose Co-transporter 2 Inhibitors and Major Adverse Cardiovascular Outcomes : A SMART-C Collaborative Meta-Analysis
BACKGROUND: Sodium glucose co-transporter 2 inhibitors (SGLT2i) consistently improve heart failure and kidney-related outcomes; however, effects on major adverse cardiovascular events (MACE) across different patient populations are less clear.
METHODS: This was a collaborative trial-level meta-analysis from the SGLT2i meta-analysis cardio-renal trialists consortium, which includes all phase 3, placebo-controlled, outcomes trials of SGLT2i across three patient populations (diabetes at high risk for atherosclerotic cardiovascular disease [ASCVD], heart failure [HF], or chronic kidney disease [CKD]). The outcomes of interest were MACE (composite of CV death, myocardial infarction [MI], or stroke), individual components of MACE (inclusive of fatal and non-fatal events), all-cause mortality, and death subtypes. Effect estimates for SGLT2i vs. placebo were meta-analyzed across trials and examined across key subgroups (established ASCVD, prior MI, diabetes, prior HF, albuminuria, CKD stages and risk groups).
RESULTS: A total of 78,607 patients across 11 trials were included: 42,568 (54.2%), 20,725 (26.4%), and 15,314 (19.5%) were included from trials of patients with diabetes at high risk for ASCVD, HF, or CKD, respectively. SGLT2i reduced the rate of MACE by 9% (HR 0.91 [95% CI 0.87-0.96], p<0.0001) with a consistent effect across all three patient populations (I2=0%) and across all key subgroups. This effect was primarily driven by a reduction in CV death (HR 0.86 [0.81-0.92], p<0.0001), with no significant effect for MI in the overall population (HR 0.95 [0.87-1.04], p=0.29), and no effect on stroke (HR 0.99 [0.91-1.07], p=0.77). The benefit for CV death was driven primarily by reductions in HF death and sudden cardiac death (HR 0.68 [0.46-1.02] and HR 0.86 [0.78-0.95], respectively) and was generally consistent across subgroups, with the possible exception of being more apparent in those with albuminuria (Pint=0.02).
CONCLUSIONS: SGLT2i reduce the risk of MACE across a broad range of patients irrespective of ASCVD, diabetes, kidney function or other major clinical characteristics at baseline. This effect is driven primarily by a reduction of CV death, particularly HF and sudden cardiac death, without a significant effect on MI in the overall population, and no effect on stroke. These data may help inform selection for SGLT2i therapies across the spectrum of cardiovascular-kidney-metabolic disease.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - year:2024 |
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| Enthalten in: |
Circulation - (2024) vom: 07. Apr. |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Patel, Siddharth M [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Revised 07.04.2024 published: Print-Electronic Citation Status Publisher |
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| doi: |
10.1161/CIRCULATIONAHA.124.069568 |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM370724968 |
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| 100 | 1 | |a Patel, Siddharth M |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Sodium Glucose Co-transporter 2 Inhibitors and Major Adverse Cardiovascular Outcomes |b A SMART-C Collaborative Meta-Analysis |
| 264 | 1 | |c 2024 | |
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| 500 | |a Date Revised 07.04.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status Publisher | ||
| 520 | |a BACKGROUND: Sodium glucose co-transporter 2 inhibitors (SGLT2i) consistently improve heart failure and kidney-related outcomes; however, effects on major adverse cardiovascular events (MACE) across different patient populations are less clear | ||
| 520 | |a METHODS: This was a collaborative trial-level meta-analysis from the SGLT2i meta-analysis cardio-renal trialists consortium, which includes all phase 3, placebo-controlled, outcomes trials of SGLT2i across three patient populations (diabetes at high risk for atherosclerotic cardiovascular disease [ASCVD], heart failure [HF], or chronic kidney disease [CKD]). The outcomes of interest were MACE (composite of CV death, myocardial infarction [MI], or stroke), individual components of MACE (inclusive of fatal and non-fatal events), all-cause mortality, and death subtypes. Effect estimates for SGLT2i vs. placebo were meta-analyzed across trials and examined across key subgroups (established ASCVD, prior MI, diabetes, prior HF, albuminuria, CKD stages and risk groups) | ||
| 520 | |a RESULTS: A total of 78,607 patients across 11 trials were included: 42,568 (54.2%), 20,725 (26.4%), and 15,314 (19.5%) were included from trials of patients with diabetes at high risk for ASCVD, HF, or CKD, respectively. SGLT2i reduced the rate of MACE by 9% (HR 0.91 [95% CI 0.87-0.96], p<0.0001) with a consistent effect across all three patient populations (I2=0%) and across all key subgroups. This effect was primarily driven by a reduction in CV death (HR 0.86 [0.81-0.92], p<0.0001), with no significant effect for MI in the overall population (HR 0.95 [0.87-1.04], p=0.29), and no effect on stroke (HR 0.99 [0.91-1.07], p=0.77). The benefit for CV death was driven primarily by reductions in HF death and sudden cardiac death (HR 0.68 [0.46-1.02] and HR 0.86 [0.78-0.95], respectively) and was generally consistent across subgroups, with the possible exception of being more apparent in those with albuminuria (Pint=0.02) | ||
| 520 | |a CONCLUSIONS: SGLT2i reduce the risk of MACE across a broad range of patients irrespective of ASCVD, diabetes, kidney function or other major clinical characteristics at baseline. This effect is driven primarily by a reduction of CV death, particularly HF and sudden cardiac death, without a significant effect on MI in the overall population, and no effect on stroke. These data may help inform selection for SGLT2i therapies across the spectrum of cardiovascular-kidney-metabolic disease | ||
| 650 | 4 | |a Journal Article | |
| 700 | 1 | |a Kang, Yu Mi |e verfasserin |4 aut | |
| 700 | 1 | |a Im, KyungAh |e verfasserin |4 aut | |
| 700 | 1 | |a Neuen, Brendon L |e verfasserin |4 aut | |
| 700 | 1 | |a Anker, Stefan D |e verfasserin |4 aut | |
| 700 | 1 | |a Bhatt, Deepak L |e verfasserin |4 aut | |
| 700 | 1 | |a Butler, Javed |e verfasserin |4 aut | |
| 700 | 1 | |a Cherney, David Z I |e verfasserin |4 aut | |
| 700 | 1 | |a Claggett, Brian L |e verfasserin |4 aut | |
| 700 | 1 | |a Fletcher, Robert A |e verfasserin |4 aut | |
| 700 | 1 | |a Herrington, William G |e verfasserin |4 aut | |
| 700 | 1 | |a Inzucchi, Silvio E |e verfasserin |4 aut | |
| 700 | 1 | |a Jardine, Meg J |e verfasserin |4 aut | |
| 700 | 1 | |a Mahaffey, Kenneth W |e verfasserin |4 aut | |
| 700 | 1 | |a McGuire, Darren K |e verfasserin |4 aut | |
| 700 | 1 | |a McMurray, John J V |e verfasserin |4 aut | |
| 700 | 1 | |a Neal, Bruce |e verfasserin |4 aut | |
| 700 | 1 | |a Packer, Milton |e verfasserin |4 aut | |
| 700 | 1 | |a Perkovic, Vlado |e verfasserin |4 aut | |
| 700 | 1 | |a Solomon, Scott D |e verfasserin |4 aut | |
| 700 | 1 | |a Staplin, Natalie |e verfasserin |4 aut | |
| 700 | 1 | |a Vaduganathan, Muthiah |e verfasserin |4 aut | |
| 700 | 1 | |a Wanner, Christoph |e verfasserin |4 aut | |
| 700 | 1 | |a Wheeler, David C |e verfasserin |4 aut | |
| 700 | 1 | |a Zannad, Faiez |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Yujie |e verfasserin |4 aut | |
| 700 | 1 | |a Heerspink, Hiddo J L |e verfasserin |4 aut | |
| 700 | 1 | |a Sabatine, Marc S |e verfasserin |4 aut | |
| 700 | 1 | |a Wiviott, Stephen D |e verfasserin |4 aut | |
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