{"doi":"10.1161/circulationaha.124.069568","title":"Sodium-Glucose Cotransporter-2 Inhibitors and Major Adverse Cardiovascular Outcomes: A SMART-C Collaborative Meta-Analysis","abstract":"BACKGROUND: Sodium-glucose cotransporter-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 3 patient populations (patients with diabetes at high risk for atherosclerotic cardiovascular disease, heart failure [HF], or chronic kidney disease). The outcomes of interest were MACE (composite of cardiovascular death, myocardial infarction , or stroke), individual components of MACE (inclusive of fatal and nonfatal events), all-cause mortality, and death subtypes. Effect estimates for SGLT2i versus placebo were meta-analyzed across trials and examined across key subgroups (established atherosclerotic cardiovascular disease, previous myocardial infarction, diabetes, previous HF, albuminuria, chronic kidney disease 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 atherosclerotic cardiovascular disease, HF, or chronic kidney disease, respectively. SGLT2i reduced the rate of MACE by 9% (hazard ration [HR], 0.91 [95% CI, 0.87–0.96], P <0.0001) with a consistent effect across all 3 patient populations ( I 2 =0%) and across all key subgroups. This effect was primarily driven by a reduction in cardiovascular death (HR, 0.86 [95% CI, 0.81–0.92], P <0.0001), with no significant effect for myocardial infarction in the overall population (HR, 0.95 [95% CI, 0.87–1.04], P =0.29), and no effect on stroke (HR, 0.99 [95% CI, 0.91–1.07], P =0.77). The benefit for cardiovascular death was driven primarily by reductions in HF death and sudden cardiac death (HR, 0.68 [95% CI, 0.46–1.02] and HR, 0.86 [95% CI, 0.78–0.95], respectively) and was generally consistent across subgroups, with the possible exception of being more apparent in those with albuminuria ( P interaction =0.02). CONCLUSIONS: SGLT2i reduce the risk of MACE across a broad range of patients irrespective of atherosclerotic cardiovascular disease, diabetes, kidney function, or other major clinical characteristics at baseline. This effect is driven primarily by a reduction of cardiovascular death, particularly HF death and sudden cardiac death, without a significant effect on myocardial infarction 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.","journal":"Circulation","year":2024,"id":416323,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":168,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.8847,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1199484,"name":"Yu Mi Kang","orcid":"0000-0002-6272-0666","position":1,"is_corresponding":false},{"id":1199485,"name":"KyungAh Im","orcid":"0000-0003-2185-6193","position":2,"is_corresponding":false},{"id":300854,"name":"Brendon L. 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Inzucchi","orcid":"0000-0003-1254-6636","position":11,"is_corresponding":false},{"id":255771,"name":"Meg Jardine","orcid":"0000-0002-0160-2375","position":12,"is_corresponding":false},{"id":75047,"name":"Kenneth W. Mahaffey","orcid":"0000-0002-3791-2148","position":13,"is_corresponding":false},{"id":74977,"name":"Darren K. McGuire","orcid":"0000-0002-6412-7989","position":14,"is_corresponding":false},{"id":2612,"name":"John J.V. McMurray","orcid":"0000-0002-6317-3975","position":15,"is_corresponding":false},{"id":923,"name":"Bruce Neal","orcid":"0000-0002-0490-7465","position":16,"is_corresponding":false},{"id":92418,"name":"Milton Packer","orcid":"0000-0003-1828-2387","position":17,"is_corresponding":false},{"id":75046,"name":"Vlado Perkovic","orcid":"0000-0002-4257-7620","position":18,"is_corresponding":false},{"id":27970,"name":"Scott D. Solomon","orcid":"0000-0003-3698-9597","position":19,"is_corresponding":false},{"id":89771,"name":"Natalie Staplin","orcid":"0000-0003-4482-4418","position":20,"is_corresponding":false},{"id":61406,"name":"Muthiah Vaduganathan","orcid":"0000-0003-0885-1953","position":21,"is_corresponding":false},{"id":74376,"name":"Christoph Wanner","orcid":"0000-0001-9507-5301","position":22,"is_corresponding":false},{"id":255779,"name":"David C. Wheeler","orcid":"0000-0003-0745-3478","position":23,"is_corresponding":false},{"id":2633,"name":"Faı̈ez Zannad","orcid":"0000-0001-7456-1570","position":24,"is_corresponding":false},{"id":754881,"name":"Yujie Zhao","orcid":"0000-0003-2896-4955","position":25,"is_corresponding":false},{"id":232682,"name":"Hiddo J.L. Heerspink","orcid":"0000-0002-3126-3730","position":26,"is_corresponding":false},{"id":50019,"name":"Marc S. Sabatine","orcid":"0000-0002-0691-3359","position":27,"is_corresponding":false},{"id":853103,"name":"Stephen D. Wiviott","orcid":"0000-0002-4922-9880","position":28,"is_corresponding":false},{"id":902203,"name":"Siddharth M. Patel","orcid":"0000-0002-4637-4361","position":0,"is_corresponding":true}],"reference_count":30,"raw_metadata":null,"created_at":"2026-07-19T01:56:20.964471Z","pmid":"38583093","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}