TUXEDO-2 (Ultrathin Strut vs Xience in a Diabetic Population With Multivessel Disease 2—India Study) è un trial randomizzato prospettico, multicentrico, in aperto, con disegno fattoriale 2 Å~ 2, condotto in ospedali indiani. Globalmente, 1.800 pazienti diabetici e con coronaropatia multivasale sono stati sottoposti a una prima randomizzazione durante PCI a ricevere una PCI con impianto di un DES a maglie ultra-sottili a rilascio di sirolimus e polimero biodegradabile, oppure un DES Xience con polimero durevole e rilascio di everolimus; inoltre, essi sono stati randomizzati a ricevere una DAPT composta da ticagrelor e ASA oppure da prasugrel e ASA per almeno 6 mesi se avevano una coronaropatia stabile, e a 1 anno se avevano una sindrome coronarica acuta (ACS) presente nel 79% dei pazienti. I risultati presentati si riferiscono a questa seconda randomizzazione. Il disegno dello studio prevedeva…

 1. Tarantini G, Honton B, Paradies V, et al. Early discontinuation of aspirin after PCI in low-risk acute myocardial infarction. N Engl J Med 2025;393:2083–94. Among low-risk patients with acute myocardial infarction who had undergone early complete revascularization and had completed 1 month of dual antiplatelet therapy without complications, P2Y12-inhibitor monotherapy was noninferior to continued dual antiplatelet therapy with respect to the occurrence of adverse cardiovascular and cere- brovascular events and resulted in a lower incidence of bleeding events. 2. Guimarães PO, Franken M, Tavares CAM, et al. Early withdrawal of aspirin after PCI in acute coronary syndromes. N Engl J Med 2025;393:2095–106. Among patients who had undergone successful PCI for acute coronary syndromes, potent P2Y12 inhibitor monotherapy was not found to be noninferior to dual antiplatelet therapy with respect to a composite of death or ischemic events at 12 months. 3. Gould KL, Johnson NP, Roby AE, et al. Optimal medical care and coronary flow capacity-guided myocardial revascularization vs usual care for chronic coronary artery disease: the CENTURY trial. Eur Heart J 2025;46:3273–86. Erratum in: Eur Heart J. 2025 Sep 2;46(33):3286 . The randomized CENTURY trial demonstrates that comprehensive integrated lifestyle modification and medical management towards goals with revascularization reserved for severely reduced CFC, significantly reduced risk factor scores, death, death or MI, and revascularization. 4. Fearon WF, Zimmermann FM, Ding VY, et al. Outcomes after fractional flow reserve-guided percutaneous coronary intervention versus coronary artery bypass grafting (FAME 3): 5-year follow-up of a multicentre, open-label, randomised trial. Lancet 2025;405:1481–90. This prespecified 5-year follow-up of FAME 3 shows no significant differences in the composite outcome of death, stroke, or myocardial infarction in 1.500 patients with three-vessel CAD not involving the left main coronary artery, although rates of myocardial infarction and repeat revascularisation remained higher with PCI. In addition, this final analysis of the trial showed no longterm accrual of benefit after CABG on a composite outcome of death, stroke, or myocardial infarction, which contradicts previous studies. 5. Ali ZA, Shin D, Vijayvergiya R. et al. Optical coherence tomography -vs angiographyguided coronary stent implantation in calcified lesions: the ILUMIEN IV trial.  Eur Heart J 2025;46:3201–10. In the ILUMIEN IV trial, OCT-guided PCI in patients with angiographically determined moderately or severely calcified lesions reduced the 2-year rate of target vessel failure compared with angiography-guided PCI, an effect that was not seen in patients with lesions with no or mild angiographic calcium.  6. Kim MC, Ahn JH, Hyun DY, et al. Immediate versus staged complete revascularisation during index admission in patients with ST-segment elevation myocardial infarction and multivessel disease (OPTION-STEMI): a multicentre, non- inferiority, open-label, randomised trial. Lancet 2025;406:1032–43. Among patients with STEMI and multivessel disease, immediate complete revascularisation was not shown to be noninferior to staged complete revascularisation during the index admission in terms of incidence of a composite of death from any cause, non-fatal myocardial infarction, or any unplanned revascularisation at 1 year. This finding might inform future clinical guidelines on the role and optimal use of immediate complete revascularisation during the index admission. 7. Nijveldt R, Maeng M, Beijnink CWH, et al. Immediate or deferred nonculprit-lesion PCI in myocardial infarction. N Engl J Med, 10.1056/NEJMoa2512918. Among patients with STEMI who have undergone successful primary PCI, immediate iFR-guided PCI was not superior to deferred cardiac stress MRI–guided PCI of nonculprit coronary-artery lesions with respect to death from any cause, recurrent myocardial infarction, or hospitalization for heart failure at 3 years.   8. Spaulding C, Krackhardt F, Bogaerts K, et al. Comparing a strategy of sirolimuseluting balloon treatment to drug-eluting stent implantation in de novo coronary lesions in all-comers: design and rationale of the SELUTION DeNovo Trial. Am Heart J 2023;258:77–84. (1-year results presented TCT 2025). SELUTION DeNovo trial is an open-label, multi-center international randomized trial comparing a strategy of PCI with sirolimuseluting balloon and provisional DES to a strategy of PCI with systematic DES on target vessel failure at one and five years. Non-inferiority will be tested at one and five years. If non-inferiority is met at five years, superiority will be tested. 9. Tchetche D, Pibarot P, Bax JJ, et al. Transcatheter vs. surgical aortic valve replacement in women: the RHEIA trial. Eur Heart J 2025;46:2079–88. Among women with severe aortic stenosis, the incidence of the composite of death, stroke, or rehospitalization at 1 year was lower with TAVI than with surgery. 10. Praz F, Borger MA, Lanz J, et al. ESC/ EACTS Guidelines for the management of valvular heart disease. Eur Heart J 2025;46: 4635–736. This is an update to: European Heart Journal, Volume 43, Issue 7, 14 February 2022, Pages 561–632, https://doi.org/10. 1093/eurheartj/ehab395.

1. Bohula EA, Marston NA, Bhatia AK. Evolocumab in patients without a previous myocardial infarction or stroke. N Engl J Med, doi.org/10.1056/NEJMoa2514428. PCSK9 inhibition with evolocumab led to a lower risk of first cardiovascular events than placebo among patients with atherosclerosis or diabetes and without a previous myocardial infarction or stroke. 2. Ballantyne CM, Gellis L, Tardif JC, et al. Efficacy and safety of oral PCSK9 inhibitor enlicitide in adults with heterozygous familial hypercholesterolemia: a randomized clinical trial. JAMA, https://doi.org/ 10.1001/ jama.2025.20620.  Among adults with heterozygous familial hypercholesterolemia, treatment with enlicitide was well tolerated and significantly reduced levels of LDL-C, apolipoprotein B, non–HDL-C, and lipoprotein(a). 3. Pacheco-Velázquez SC, Oleaga C, et al. LDL-bound PCSK9 has a slower clearance kinetic and higher use for HSPGs than free- PCSK9-brief report. Arterioscler Thromb Vasc Biol 2025;45:1565–73. https://doi. org/10.1161/ATVBAHA.124.322334. Hepatic heparan sulfate proteoglycans (HSPGs) accelerate the clearance of PCSK9 (proprotein convertase subtilisin/kexin type 9). The clearance rate of plasma LDL-bound PCSK9 is slower than the clearance rate of its free form. The HSPG syndecan-1 modestly contributes to PCSK9 clearance through an LDLR-independent pathway.  4. Laffin LJ, Nicholls SJ, Scott RS, et al. Phase 1 trial of CRISPR-cas9 gene editing targeting ANGPTL3. N Engl J Med 2025; 393:2119–30. Angiopoietin-like protein 3 (ANGPTL3) inhibits lipoprotein and endothelial lipases. ANGPTL3 loss-of-function genetic variants are associated with decreased levels of low-density lipoprotein cholesterol and triglycerides and a decreased lifetime risk of atherosclerotic cardiovascular disease. Editing of ANGPTL3 was associated with few adverse events and resulted in reductions from baseline in ANGPTL3 levels. 5. Zheutlin AR, Handoo F, Luebbe S, et al. Cumulative exposure to atherogenic lipoprotein particles in young adults and subsequent incident atherosclerotic cardiovascular disease. Eur Heart J 2025; 46:4302–12. Cumulative exposure to atherogenic lipid particles in young adulthood increases the risk for incident atherosclerotic cardiovascular disease later in life. Apolipoprotein B concentration <75 mg/dL may represent a goal to maintain low risk in young adults. 6. Nicholls SJ, Nelson AJ, Ditmarsch M, Kastelein JJP, Ballantyne CM, Ray KK, et al. Safety and efficacy of obicetrapib in patients at high cardiovascular risk. N Engl J Med 2025;393: 51–61. Among patients with atherosclerotic cardiovascular disease or heterozygous familial hypercholesterolemia who were receiving maximum tolerated doses of lipidlowering therapy and were at high risk for cardiovascular events, obicetrapib reduced LDL cholesterol levels by 29.9%. 7. Christensen JJ, Holven KB, Bogsrud MP, et al. Statin use in pregnancy and risk of congenital malformations: a Norwegian nationwide study. Eur Heart J, https://doi.  org/10.1093/eurheartj/ ehaf592. In this large, nationwide study and updated meta-analysis, no significant association was observed between first-trimester exposure to statins or other lipid-modifying agents and congenital malformations. Although limited power may have prevented detection of weak but clinically relevant associations, the findings do not support a strong or independent association between statin exposure in pregnancy and congenital malformations. 8. Marston NA, Bergmark BA, Alexander VJ, et al. Olezarsen for managing severe hypertriglyceridemia and pancreatitis risk. N Engl J Med 2026;394:429-441. doi:10.1056/NEJMoa2512761. Among patients with severe hypertriglyceridemia, treatment with olezarsen led to a significantly greater reduction in the triglyceride level at 6 months and in the incidence of acute pancreatitis than placebo.  9. MacDougall DE, Tybjærg-Hansen A, et al. Lipoprotein(a) and recurrent atherosclerotic cardiovascular events: the US family heart database. Eur Heart J 2025; 46:4762–75. In 273.770 individuals with atherosclerotic cardiovascular disease (ASCVD), higher lipoprotein(a) levels were associated with continuously increasing risk of recurrent ASCVD events regardless of sex and race/ ethnicity that may have been partially mitigated by high impact LDL cholesterollowering therapy. 10. Kindborg G, Eriksson Hogling D, et al. Major cardiovascular events in first degree relatives of individuals with elevated plasma lipoprotein(a): a registrybased cohort study. Eur Heart J, https:// doi.org/10.1093/eurheartj/ehaf677. First-degree relatives of individuals with elevated Lp(a) levels have a higher incidence of MACE. Cascade screening could be a feasible strategy to identify first-degree relatives at heightened risk.

Lo studio (ORBITA-STAR) ha arruolato 51 pazienti (età media 63±9 anni, il 78% era rappresentato da uomini, l’FFR mediana era 0.68 (0.57–0.79), la iFR mediana era 0.80 (0.48–0.89) e la CFR mediana 1.42 (1.08–1.85). I pazienti avevano sintomi anginosi e stenosi isolata di almeno il 70% dell’arteria discendente anteriore alla coronarografia o alla TC coronarica, ed erano avviati a intervento di rivascolarizzazione percutanea. Il protocollo prevedeva che i pazienti sospendessero per 2 settimane prima, del ricovero, i farmaci antianginosi e riportassero immediatamente i sintomi anginosi su una applicazione del proprio smartphone. Prima della procedura di PCI, veniva posizionata…

Meta-analisi di 24 studi farmaco-epidemiologici, pubblicati tra il 2016 e il 2023, che includono informazioni e stime di rischio riguardanti l’uso di cannabis sulla mortalità cardiovascolare, sull’infarto miocardico non fatale, sindromi coronariche acute e stroke. Dei 24 studi, 17 erano trasversali, 6 di coorte e 1 “casocontrollo”. Sono state eseguite stime aggregate  del rischio con modello a effetti “random” e valutazione della varianza inversa. In tutti gli studi, i soggetti analizzati utilizzavano cannabis per uso ricreativo…

Studio condotto in 50 centri coreani ad alto volume. I pazienti arruolati sono stati suddivisi in due strati a seconda che avessero presenza di HBR (n=1.598) in base ai criteri dell’Academic Research Consortium, o non-HBR (n=3.299). I primi avevano un’età più avanzata (mediana 76 vs 64) con una maggior rappresentanza di sesso femminile (33% vs 21%). Più frequente tra gli HBR anche l’ipertensione (78% vs 61%), soprattutto il diabete (53% vs 32%) la nefropatia cronica (32% vs 2%) e la fibrillazione atriale (20% vs 1%). Il valore di Hb era 11.5 g/dl vs 14.2 g/dl. I pazienti trivasali erano il 65% tra gli HBR e il 54% nei non-HBR senza differenze sostanziali nella complessità delle lesioni (e con un utilizzo simile di imaging intracoronarico, circa il 40% dei casi). Le ACS rappresentavano il 60% negli HBR vs 53% nei non-HBR. I pazienti HBR sono stati randomizzati a DAPT di 1 mese versus 3 mesi, mentre i non-HBR a DAPT di 3 mesi versus 12 mesi. Per la DAPT era prevalentemente utilizzato clopidogrel (91% dei pazienti HBR e 76% nei pazienti non-HBR). L’uso di anticoagulanti era più elevato nei pazienti HBR (17% vs 0%). Nei pazienti in cui la DAPT veniva sospesa prima del 12esimo mese, la monoterapia successiva consisteva in clopidogrel nel 68% dei casi, ASA nel 23% e in prasugrel/ticagrelor nel 9% dei casi. Vi erano tre endpoint primari…

Lo studio randomizzato in aperto (ma con aggiudicazione degli eventi in cieco) condotto in 15 centri italiani tra novembre 2017 e giugno 2023, ha arruolato 320 pazienti sottoposti a TAVI che presentavano lesioni intermedie (tra 50 e 90% per valutazione visiva). I pazienti sono stati randomizzati alla guida FFR (“gruppo FFR”, n=164, nei quali le lesioni con valori ≤0.80 venivano trattate, mentre quelle in cui era compresa tra 0.81 e 0.85 venivano riconsiderate con ulteriore FFR dopo TAVI, mentre se l’FFR era >0.85 la PCI veniva differita) oppure alla guida angiografica (n=156). In tutti erano impiantate protesi SAPIEN 3 e SAPIEN 3 ULTRA. L’età mediana risultava di 86 anni, due terzi erano donne, l’STS score era 3% e il SYNTAX score era 7. Una classe NYHA III-IV era presente nel 52% del “gruppo FFR” e nel 58% del “gruppo angio”. La PCI veniva eseguita in 99 pazienti (60%) del “gruppo FFR” (con una rivascolarizzazione funzionale completa nel 99% dei casi) e in 141 (91%) nel “gruppo angio” con una rivascolarizzazione anatomica completa nel 75% dei casi. La mediana di stent impiantati per procedura è…