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Background: Patients with heart failure (HF) and a recent worsening heart failure (WHF) event are known to be at high risk of recurrent hospitalization and death, regardless of ejection fraction., Objectives: This study examined the efficacy and safety of the nonsteroidal mineralocorticoid receptor antagonist (MRA) finerenone in relation to the recency of a WHF event., Methods: FINEARTS-HF (FINerenone trial to investigate Efficacy and sAfety superioR to placebo in paTientS with Heart Failure) was a randomized, double-blind, placebo-controlled trial of finerenone in patients with HF and left ventricular ejection fraction ≥40%. In this prespecified analysis, we assessed the risk of cardiovascular (CV) events and response to finerenone vs placebo in relation to the time from WHF to randomization (during or within 7 days, 7 days to 3 months, >3 months, or no prior WHF). The primary outcome was a composite of total (first and recurrent) WHF events and CV death, analyzed using a proportional rates method., Results: Of 6,001 patients validly randomized to finerenone or placebo, 1,219 (20.3%) were enrolled during (749 [12.5%]) or within 7 days (470 [7.8%]), 2,028 (33.8%) between 7 days and 3 months, and 937 (15.6%) >3 months from a WHF event; 1,817 (30.3%) had no prior history of WHF. Rates of the primary composite outcome varied inversely with time since WHF, with >2-fold higher risk in those enrolled during or within 7 days of WHF compared with those enrolled >3 months from WHF or without prior WHF (risk ratio [RR]: 2.13; 95% CI: 1.82-2.55). Compared to placebo, finerenone appeared to lower the risk of the primary composite to a greater extent in those enrolled within 7 days of WHF (RR: 0.74; 95% CI: 0.57-0.95) or between 7 days and 3 months of WHF (RR: 0.79; 95% CI: 0.64-0.97) than in those >3 months from WHF or without prior WHF (RR: 0.99; 95% CI: 0.81-1.21); however, no definitive treatment-by-time interaction could be confirmed (P = 0.07). Greater absolute risk reductions with finerenone were accordingly seen in those with recent WHF (P trend  = 0.011). The risk of adverse events including hyperkalemia and worsening renal function among patients assigned to finerenone was not increased in those with recent WHF., Conclusions: Compared with those without recent WHF, patients with HF and mildly reduced or preserved ejection fraction who have experienced a recent WHF event are at higher risk for recurrent HF events and CV death; a possible signal of enhanced absolute treatment benefit with finerenone in this population requires further confirmation in future studies. (Study to Evaluate the Efficacy [Effect on Disease] and Safety of Finerenone on Morbidity [Events Indicating Disease Worsening] & Mortality [Death Rate] in Participants With Heart Failure and Left Ventricular Ejection Fraction [Proportion of Blood Expelled Per Heart Stroke] Greater or Equal to 40% [FINEARTS-HF], NCT04435626; A study to gather information on the influence of study drug finerenone on the number of deaths and hospitalizations in participants with heart failure EudraCT 2020-000306-29)., Competing Interests: Funding Support and Author Disclosures The FINEARTS-HF trial was funded by Bayer AG. Dr Desai has received institutional research grants (to Brigham and Women’s Hospital) from Abbott, Alnylam, AstraZeneca, Bayer, Novartis, and Pfizer; and has received personal consulting fees from Abbott, Alnylam, AstraZeneca, Bayer, Biofourmis, Boston Scientific, Medpace, Medtronic, Merck, Novartis, Parexel, Porter Health, Regeneron, River2Renal, Roche, Veristat, Verily, and Zydus. Dr Vaduganathan has received research grant support, served on advisory boards, or had speaker engagements with American Regent, Amgen, AstraZeneca, Bayer AG, Baxter Healthcare, Bristol Myers Squibb, Boehringer Ingelheim, Chiesi, Cytokinetics, Fresenius Medical Care, Idorsia Pharmaceuticals, Lexicon Pharmaceuticals, Merck, Milestone Pharmaceuticals, Novartis, Novo Nordisk, Pharmacosmos, Relypsa, Roche Diagnostics, Sanofi, and Tricog Health; and participates on clinical trial committees for studies sponsored by AstraZeneca, Galmed, Novartis, Bayer AG, Occlutech, and Impulse Dynamics. Dr Claggett has received personal consulting fees from Alnylam, Bristol Myers Squibb, Cardior, Cardurion, Corvia, CVRx, Eli Lilly, Intellia, and Rocket; and has served on a data safety monitoring board for Novo Nordisk. Dr Jhund has received speaker fees from AstraZeneca, Novartis, Alkem Metabolics, ProAdWise Communications, and Sun Pharmaceuticals; has received advisory board fees from AstraZeneca, Boehringer Ingelheim, and Novartis; has received research funding from AstraZeneca, Boehringer Ingelheim, Analog Devices Inc, and Roche Diagnostics; his employer, the University of Glasgow, has been remunerated for clinical trial work from AstraZeneca, Bayer AG, Novartis, and Novo Nordisk; and he is Director of GCTP Ltd. Dr Cunningham has received personal consulting fees from Roche Diagnostics, Occlutech, KCK, and Edgewise Therapeutics. Mr Lay-Flurrie is a full-time employee of Bayer PLC, Research and Development, Pharmaceuticals. Drs Borentain, Viswanathan, Rohwedder, and Amarante are employees of Bayer AG. Dr Lam has received research support from Novo Nordisk and Roche Diagnostics; has received consulting fees from Alleviant Medical, Allysta Pharma, AnaCardio AB, Applied Therapeutics, AstraZeneca, Bayer, Biopeutics, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, CardioRenal, CPC Clinical Research, Eli Lilly, Impulse Dynamics, Intellia Therapeutics, Ionis Pharmaceutical, Janssen Research and Development LLC, Medscape/WebMD Global LLC, Merck, Novartis, Novo Nordisk, Prosciento Inc, Quidel Corporation, Radcliffe Group Ltd, Recardio Inc, ReCor Medical, Roche Diagnostics, Sanofi, Siemens Healthcare Diagnostics, and Us2.ai; and is a cofounder and nonexecutive director of Us2.ai. Dr Senni has served on advisory boards for and received consultancy and honoraria from Novartis, Abbott, Merck, MSD, Vifor, AstraZeneca, Cardurion, Novo Nordisk, Bayer, and Boehringer Ingelheim. Dr Shah has received research grants from National Institutes of Health (U54 HL160273, X01 HL169712, R01 HL140731, R01 HL149423), American Heart Association (24SFRNPCN1291224), AstraZeneca, Corvia, and Pfizer; and has received consulting fees from Abbott, Alleviant, AstraZeneca, Amgen, Aria CV, Axon Therapies, Bayer, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Cyclerion, Cytokinetics, Edwards Lifesciences, Eidos, Imara, Impulse Dynamics, Intellia, Ionis, Lilly, Merck, MyoKardia, Novartis, Novo Nordisk, Pfizer, Prothena, Regeneron, Rivus, Sardocor, Shifamed, Tenax, Tenaya, and Ultromics. Dr Voors’ employer has received consultancy fees and/or research support from Adrenomed, Anacardio, AstraZeneca, Bayer AG, Bristol Myers Squibb, Boehringer Ingelheim, Corteria, Eli Lilly, Merck, Moderna, Novartis, Novo Nordisk, Roche Diagnostics, and SalubrisBio. Dr Zannad has received personal fees from 89Bio, Abbott, Acceleron, Applied Therapeutics, Bayer, Betagenon, Boehringer, Bristol Myers Squibb, CVRx, Cambrian, Cardior, Cereno Pharmaceutical, Cellprothera, CEVA, Inventiva, KBP, Merck, Novo Nordisk, Owkin, Otsuka, Roche Diagnostics, Northsea, and USa2; has stock options at G3Pharmaceutical and equities at Cereno, Cardiorenal, and Eshmoun Clinical research; and is the founder of Cardiovascular Clinical Trialists. Dr Pitt is a consultant for Bayer, AstraZeneca, Boehringer Ingelheim, Lexicon, Bristol Myers Squibb, KBP Biosciences, Sarfez Pharmaceuticals, SQinnovations, G3 Pharmaceuticals, Sea Star Medical, Vifor Prointel, and Brainstorm Medical; has stock/stock options in KBP Biosciences, Sarfez Pharmaceuticals, SQinnovations, G3 Pharmaceuticals, Sea Star Medical, Vifor Prointel, and Brainstorm Medical; and holds U.S. Patent 9931412, site specific delivery of eplerenone to the myocardium, and U.S. Patent pending 63/045,783 Histone modulating agents for the prevention and treatment of organ failure. Dr Kosiborod has received grants, personal fees, and other from AstraZeneca and Vifor Pharma; has received grants and personal fees from Boehringer Ingelheim and Pfizer; has received personal fees from 35Pharma, Alnylam, Amgen, Applied Therapeutics, Arrowhead Pharmaceuticals, Bayer, Cytokinetics, Dexcom, Eli Lilly, Esperion Therapeutics, Imbria Pharmaceuticals, Janssen, Lexicon Pharmaceuticals, Merck (Diabetes and Cardiovascular), Novo Nordisk, Pharmacosmos, Regeneron, Sanofi, scPharmaceuticals, Structure Therapeutics, and Youngene Therapeutics; and other from Artera Health, Saghmos Therapeutics, outside of the submitted work. Dr McMurray has received payments through Glasgow University for work on clinical trials; has consulted for and received grants from Amgen, AstraZeneca, Bayer, Cardurion, Cytokinetics, GlaxoSmithKline, and Novartis; and has received personal consultancy fees from Alnylam Pharmaceuticals, Amgen, AnaCardio, AstraZeneca, Bayer, Berlin Cures, Bristol Myers Squibb, Cardurion, Cytokinetics, Ionis Pharmaceuticals, Novartis, Regeneron Pharmaceuticals, River 2 Renal Corp, British Heart Foundation, National Institute for Health, National Heart, Lung, and Blood Institute, Boehringer Ingelheim, SQ Innovations, and the Catalyze Group; has received personal lecture fees from Abbott, Alkem Metabolics, AstraZeneca, Blue Ocean Scientific Solutions Ltd, Boehringer Ingelheim, Canadian Medical and Surgical Knowledge, Emcure Pharmaceuticals Ltd, Eris Lifesciences, European Academy of CME, Hikma Pharmaceuticals, Imagica Health, Intas Pharmaceuticals, J.B. Chemicals and Pharmaceuticals Ltd, Lupin Pharmaceuticals, Medscape/Heart.Org., ProAdWise Communications, Radcliffe Cardiology, Sun Pharmaceuticals, The Corpus, Translation Research Group, and Translational Medicine Academy; has served on the Data Safety Monitoring Board of WIRB-Copernicus Group Clinical Inc; and is a director of Global Clinical Trial Partners Ltd. Dr Solomon has received research grants from Alexion, Alnylam, AstraZeneca, Bellerophon, Bayer, Bristol Myers Squibb, Boston Scientific, Cytokinetics, Edgewise, Eidos, Gossamer, GlaxoSmithKline, Ionis, Lilly, MyoKardia, National Institutes of Health, National Heart, Lung, and Blood Institute, Novartis, Novo Nordisk, Respicardia, Sanofi Pasteur, Theracos, and US2.AI; and has consulted for Abbott, Action, Akros, Alexion, Alnylam, Amgen, Arena, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Cardior, Cardurion, Corvia, Cytokinetics, Daiichi-Sankyo, GlaxoSmithKline, Lilly, Merck, Myokardia, Novartis, Roche, Theracos, Quantum Genomics, Janssen, Cardiac Dimensions, Tenaya, Sanofi-Pasteur, Dinaqor, Tremeau, CellProThera, Moderna, American Regent, Sarepta, Lexicon, Anacardio, Akros, and Valo. Dr Kulac has reported that he has no relationships relevant to the contents of this paper to disclose., (Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: We performed a meta-analysis of randomized trials that enrolled ST-segment elevation myocardial infarction patients treated with fibrinolysis to assess the potential benefits of: 1) rescue percutaneous coronary intervention (PCI) versus no PCI; 2) systematic and early (< or =24 h) PCI versus delayed or ischemia-guided PCI; 3) fibrinolysis-facilitated PCI versus primary PCI alone., Background: The impact of PCI strategies after fibrinolysis on mortality or reinfarction remains to be established., Methods: The meta-analysis was performed using the odds ratio (OR) as the parameter of efficacy with a random effect model. Fifteen randomized trials (5,253 patients) were selected. The primary end point was mortality or the combined end point of death or reinfarction., Results: Rescue PCI for failed fibrinolysis reduced mortality (6.9% vs. 10.7%) (OR, 0.63; 95% confidence interval [CI], 0.39 to 0.99; p = 0.055) and the rate of death or reinfarction (10.8% vs. 16.8%) (OR, 0.60; 95% CI, 0.41 to 0.89; p = 0.012) compared with a conservative approach. Systematic and early PCI performed during the "stent era" led to a nonsignificant reduction in mortality compared with delayed or ischemia-guided PCI (3.8% vs. 6.7%) (OR, 0.56; 95% CI, 0.29 to 1.05; p = 0.07) and to a 2-fold reduction in the rate of death or reinfarction (7.5% vs. 13.2%) (OR, 0.53; 95% CI, 0.33 to 0.83; p = 0.0067). This benefit contrasted with a nonsignificant increase in the rate of both mortality (5.5% vs. 3.9%, p = 0.33) or death or reinfarction (9.6% vs. 5.7%, p = 0.06) observed in the "balloon era." Fibrinolysis-facilitated PCI was associated with more reinfarction as compared with primary PCI alone (5.0% vs. 3.0%) (OR, 1.68; 95% CI, 1.12 to 2.51; p = 0.013) without significant impact on mortality (OR, 1.30; 95% CI, 0.92 to 1.83; p = 0.13)., Conclusions: Our findings support rescue PCI and systematic and early PCI after fibrinolysis. However, the current data do not support fibrinolysis-facilitated PCI in lieu of primary PCI alone.