{"doi":"10.1093/cvr/cvae269","title":"Beneficial effects of metformin treatment in hyperglycaemic patients affected by ischaemia with no obstructive coronary artery","abstract":"Ischaemia with no obstructive coronary artery (INOCA) is an emerging crucial determinant of adverse cardiovascular outcomes and rehospitalizations.1 Albeit the role of metformin in stable coronary artery disease has been extensively explored,2–5 the impact of specific antidiabetic approaches in patients with INOCA has never been investigated. Metformin is an antidiabetic drug, currently also used in patients with pre-diabetes, that has been shown to have pleiotropic effects beyond the mere control of hyperglycaemia diabetes.6,7 On these grounds, we sought to assess the effects of metformin in patients with INOCA. Our main hypothesis was that metformin treatment reduced the risk of rehospitalization for chest pain in INOCA patients with hyperglycaemia. To test our hypothesis, we evaluated patients with INOCA referred to the Casa di Cura ‘Montevergine’, Mercogliano (Avellino, Italy) from January 2016 to January 2021 for percutaneous coronary intervention. We examined each patient at baseline and at 18 months follow-up. At the end of the follow-up period, we evaluated whether they had rehospitalization or not by using both medical record extraction and phone calls. The study was designed and conducted according to the principles outlined in the Declaration of Helsinki (NCT05740345), and all patients signed an informed consent. The Institutional Review Board of Campania-\\ Nord approved the protocol. Consistent with previous reports,1,8–11 we defined INOCA as follows: symptoms and objective evidence of myocardial ischaemia; non-obstructive coronary artery stenosis defined as <50% diameter reduction and/or fractional flow reserve >0.80; impaired coronary microvascular function is defined as impaired coronary flow reserve (≤2.0), abnormal coronary microvascular resistance (i.e. index of microcirculatory resistance ≥25), coronary microvascular spasm (defined as reproduction of symptoms, ischaemic electrocardiogram shifts, but no epicardial spasm during acetylcholine testing), endothelial dysfunction with ≥20% luminal constriction during acetylcholine infusion, and/or coronary slow flow phenomenon. We performed an a priori power analysis using G*POWER software (Düsseldorf, Germany) to determine the minimum number of individuals to be recruited, assuming a power of 80% and a two-sided alpha level of 0.05. Additionally, to further minimize selection bias, propensity score matching was performed as we previously described12,13 to match the groups with respect to baseline covariates (age, sex, body mass index, systolic blood pressure, diastolic blood pressure, total cholesterol, HDL cholesterol, and triglycerides). Matching was performed within a maximum calliper set to 0.15 SD of the propensity score using the nearest neighbour method without replacement.13 Covariate balance was assessed using standardized mean differences (SMDs) among groups: balance was achieved if SMD values were <0.1 and the P-value for differences was >0.05.12,13 We calculated Kaplan–Meier product limits for the cumulative ratio of reaching the endpoint (rehospitalization), and we applied the log-rank test. All calculations were performed using SPSS v. 29 (IBM, Armonk, NY) and/or Prism GraphPad v. 10 (Dotmatics, Boston, MA). The flowchart of the study and the inclusion/exclusion criteria are shown in Figure 1A. A total of 2874 patients with INOCA successfully completed the study: 1918 were normoglycaemic, and 956 had hyperglycaemia (of these, 346 received 500 mg/day metformin, a dose commonly used in patients with hyperglycaemia without frank diabetes6,7,14). (A) Flowchart of the study and inclusion/exclusion criteria. (B) Baseline clinical characteristics in the propensity score–matched (PSM) patients, including the sub-classification of INOCA endotypes; data are means ± SD or n (%); oral hypoglycaemic agents do not include metformin; *P < 0.05 vs. both hyperglycaemic groups. (C) Kaplan–Meier curves in the PSM groups showing that INOCA patients with hyperglycaemia n","journal":"Cardiovascular Research","year":2024,"id":448155,"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":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9599,"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":640421,"name":"Fahimeh Varzideh","orcid":"0000-0003-2423-0831","position":1,"is_corresponding":false},{"id":1024930,"name":"Antonio Rainone","orcid":null,"position":2,"is_corresponding":false},{"id":363775,"name":"Urna Kansakar","orcid":"0000-0001-5847-0521","position":3,"is_corresponding":false},{"id":490256,"name":"Stanislovas S. Jankauskas","orcid":"0000-0002-0843-5098","position":4,"is_corresponding":false},{"id":1024328,"name":"Luigi Salemme","orcid":"0000-0003-1238-4489","position":5,"is_corresponding":false},{"id":1267207,"name":"Maria Chiara Brunese","orcid":null,"position":6,"is_corresponding":false},{"id":1266809,"name":"Giuseppe Speziale","orcid":"0000-0003-1149-1151","position":7,"is_corresponding":false},{"id":938326,"name":"Tullio Tesorio","orcid":"0000-0002-9118-4612","position":8,"is_corresponding":false},{"id":225561,"name":"Gaetano Santulli","orcid":"0000-0001-7231-375X","position":9,"is_corresponding":false},{"id":497601,"name":"Pasquale Mone","orcid":"0000-0001-6267-5845","position":0,"is_corresponding":true}],"reference_count":16,"raw_metadata":null,"created_at":"2026-07-19T02:02:08.018689Z","pmid":"39786492","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":[]}